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mechanism action

Ibragim Gaidarov, John Adams, John Frazer, Todd Anthony, Xiaohua Chen, Joel Gatlin, Graeme Semple, David J Unett
Angiotensin (1-7) has been reported to be a ligand for the GPCR MAS1. Small molecule MAS1 modulators have also been recently characterized. Aside from convincing evidence for MAS1 activation of Gq signaling, little is known about MAS1 mediated signaling pathways initiated by these ligands, especially Ang (1-7). We performed a comprehensive characterization of recombinant MAS1 signaling induced by Ang (1-7) and small molecule ligands through numerous G protein-dependent and independent pathways, and in a signaling pathway agnostic approach...
June 18, 2018: Cellular Signalling
Hai-Yun Wu, Xiao-Fang Mao, Xue-Qi Tang, Usman Ali, Evhy Apryani, Hao Liu, Xin-Yan Li, Yong-Xiang Wang
Interleukin 10 (IL-10) is antinociceptive in various animal models of pain without induction of tolerance, and its mechanism of action was generally believed to be mediated by inhibition of neuroinflammation. Here we reported that intrathecal IL-10 injection dose dependently attenuated mechanical allodynia and thermal hyperalgesiain male and female neuropathic rats, with ED50 values of 40.8 ng and 24 ng, and Emax values of 61.5% MPE and 100% MPE in male rats. Treatment with IL-10 specifically increased expression of the β-endorphin (but not prodynorphin) gene and protein in primary cultures of spinal microglia but not in astrocytes or neurons...
June 18, 2018: Brain, Behavior, and Immunity
Parisa Zargar, Esmaeel Ghani, Farideh Jalali Mashayekhi, Amin Ramezani, Ebrahim Eftekhar
5-Fluorouracil (5-FU)-based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5-FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5-FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5-FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay...
June 2018: Oncology Letters
Sen Lu, Caizhao Lin, Xiaobin Cheng, Hanju Hua, Tao Xiang, Yu Huang, Xi Huang
It has previously been reported that cardamonin is able to regulate glycometabolism and vasodilation whilst also exhibiting anti-inflammatory and antitumor properties. The antitumor effect of cardamonin is multifaceted, and so it is necessary to investigate the antitumor mechanisms of cardamonin at the molecular level. Cardamonin alters chemotherapy-resistant colon cancer cell growth; however, the underlying mechanism is unknown. The present study was conducted to investigate the effect of cardamonin on chemotherapy-resistant colon cancer cells and the possible mechanisms of action...
June 2018: Oncology Letters
Alexander G Truesdell, Behnam Tehrani, Ramesh Singh, Shashank Desai, Patricia Saulino, Scott Barnett, Stephen Lavanier, Charles Murphy
The incidence of cardiogenic shock is rising, patient complexity is increasing and patient survival has plateaued. Mirroring organisational innovations of elite military units, our multidisciplinary medical specialists at the INOVA Heart and Vascular Institute aim to combine the adaptability, agility and cohesion of small teams across our large healthcare system. We advocate for widespread adoption of our 'combat' methodology focused on: increased disease awareness, early multidisciplinary shock team activation, group decision-making, rapid initiation of mechanical circulatory support (as appropriate), haemodynamic-guided management, strict protocol adherence, complete data capture and regular after action reviews, with a goal of ending preventable death from cardiogenic shock...
May 2018: Interventional Cardiology
Vishvanath Tiwari, Neha Mishra, Keval Gadani, P S Solanki, N A Shah, Monalisa Tiwari
Acinetobacter baumannii is a multi-drug resistant opportunistic pathogen, which causes respiratory and urinary tract infections. Its prevalence increases gradually in the clinical setup. Carbapenems (beta-lactam) are most effective antibiotics till now against A. baumannii , but the development of resistance against it may lead to high mortality. Therefore, it is of utmost importance to develop an alternative drug against A. baumannii . In the present study, we have synthesized ZnO nanoparticle (ZnO-NP) and characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and UV-Visible spectroscopy...
2018: Frontiers in Microbiology
Rajani Thanissery, Daina Zeng, Raul G Doyle, Casey M Theriot
Antibiotics are considered to be the first line of treatment for mild to moderately severe Clostridium difficile infection (CDI) in humans. However, antibiotics are also risk factors for CDI as they decrease colonization resistance against C. difficile by altering the gut microbiota and metabolome. Finding compounds that selectively inhibit different stages of the C. difficile life cycle, while sparing the indigenous gut microbiota is important for the development of alternatives to standard antibiotic treatment...
2018: Frontiers in Microbiology
Guoyu Huang, Guanbao Zhu
Several members of the sirtuin (SIRT) family, a highly conserved family of NAD+ -dependent enzymes, have been shown to play a critical role in both promoting and/or suppressing tumorigenesis. In this study, recent progress in the field concerning SIRT4 and cancer was reviewed, and the relationship between SIRT4 and tumors was investigated. Subsequently, we evaluated the role of SIRT4 with oncogenic or tumor-suppressive activity in cancer, which may provide insight in identifying the underlying mechanism of action of SIRT4 in cancer...
2018: OncoTargets and Therapy
Donald P Tashkin, Nicholas J Gross
Long-acting muscarinic antagonists (LAMAs), along with long-acting β2 -agonists (LABAs), are the mainstay for treatment of patients with COPD. Glycopyrrolate, or glycopyrronium bromide, like other LAMAs, inhibits parasympathetic nerve impulses by selectively blocking the binding of acetylcholine to muscarinic receptors. Glycopyrrolate is unusual in that it preferentially binds to M3 over M2 muscarinic receptors, thereby specifically targeting the primary muscarinic receptor responsible for bronchoconstriction occurring in COPD...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Eusondia Arnett, Ashlee M Weaver, Kiersten C Woodyard, Maria J Montoya, Michael Li, Ky V Hoang, Andrew Hayhurst, Abul K Azad, Larry S Schlesinger
Peroxisome proliferator-activated receptor (PPAR)γ is a global transcriptional regulator associated with anti-inflammatory actions. It is highly expressed in alveolar macrophages (AMs), which are unable to clear the intracellular pathogen Mycobacterium tuberculosis (M.tb). Although M.tb infection induces PPARγ in human macrophages, which contributes to M.tb growth, the mechanisms underlying this are largely unknown. We undertook NanoString gene expression analysis to identify novel PPARγ effectors that condition macrophages to be more susceptible to M...
June 2018: PLoS Pathogens
Daniel Pletzer, Sarah C Mansour, Robert E W Hancock
With the antibiotic development pipeline running dry, many fear that we might soon run out of treatment options. High-density infections are particularly difficult to treat due to their adaptive multidrug-resistance and currently there are no therapies that adequately address this important issue. Here, a large-scale in vivo study was performed to enhance the activity of antibiotics to treat high-density infections caused by multidrug-resistant Gram-positive and Gram-negative bacteria. It was shown that synthetic peptides can be used in conjunction with the antibiotics ciprofloxacin, meropenem, erythromycin, gentamicin, and vancomycin to improve the treatment outcome of murine cutaneous abscesses caused by clinical hard-to-treat pathogens including all ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae) pathogens and Escherichia coli...
June 2018: PLoS Pathogens
Manjusha Thakar, Yue Hu, Michael Morreale, Lane Lerner, Wan Ying Lin, Rupashree Sen, Yi Cai, Enusha Karunasena, Maya Thakar, Soren Saggi, Harold Keer, Nita Ahuja
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations...
2018: PloS One
Weili Xu, Suolin Li, Fengxue Yu, Yongting Zhang, Xiaofeng Yang, Wenting An, Wenbo Wang, Chi Sun
BACKGROUND: Propranolol (PRO) is the first-line drug for infantile hemangioma treatment. However, its mechanism of action remains unclear. Nuclear factor-kappa B (NF-κB) is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 (TSP-1) is the most important anti-angiogenesis protein in vivo. These proteins mediate signaling pathways, probably playing an important role in hemangioma treatment. This study explored the synergistic regulation of TSP-1 and NF-κB signaling pathways in the treatment of hemangioma with PRO...
June 12, 2018: Plastic and Reconstructive Surgery
Fan Bai, Xuewu Chen, Hui Yang, Hong-Guang Xu
Tumor necrosis factor (TNF) -α plays a crucial role in rheumatoid arthritis (RA)-related bone loss disease. The main mechanism of action of RA induced bone loss is the significant inhibitory effect of TNF-α on osteoblast differentiation. TNF-α inhibits osteoblast differentiation mainly by activating nuclear factor (NF) -κB signaling pathway. Owing to the crucial role of TNF-α and NF-κB in the inhibition of osteoblast differentiation, they are considered as targets for the development of therapeutic drugs...
June 20, 2018: Journal of Craniofacial Surgery
Ernest R Blatchley, John Cullen, Brian Petri, Keith Bircher, Nicholas Welschmeyer
The shipping industry is critical to international commerce; however, contemporary shipping practices involve uptake and discharge of ballast water, which introduces the potential for transfer of non-indigenous, invasive species among geographically distinct habitats. To counteract this hazard, regulations for ballast water management have been implemented by the International Maritime Organization (IMO) and by regulatory agencies such as the United States Coast Guard (USCG). IMO and USCG discharge standards are numerically identical, but involve different definitions of treatment endpoints, which are based on fundamentally-different biological assays for quantification of ballast water treatment effectiveness...
June 21, 2018: Environmental Science & Technology
Srinivasa Reddy Bonam, Seng Wu Yuan, Lakshmi Tunki, Ranjithkumar Chellian, Sampath Kumar Halmuthur M, Sylviane Muller, Vijayapandi Pandy
Several modern treatment strategies have been adopted to combat cancer with the aim of minimizing toxicity. Medicinal plant-based compounds with the potential to treat cancer have been widely studied in preclinical research and have elicited many innovative ways of leading-edge clinical research. In parallel, researchers have eagerly tried to reduce the toxicity of current chemotherapeutic agents either by combining them with herbals or in using herbals alone. The focus of this article is to present an update of medicinal plants and their bioactive compounds, or mere changes in the bioactive compounds, and herbal edibles, which display efficacy against diverse cancer cells and in anticancer therapy...
June 21, 2018: ChemMedChem
Holly P Kennedy, Melissa Cheyney, Hannah G Dahlen, Soo Downe, Maralyn J Foureur, Caroline S E Homer, Elaine Jefford, Alison McFadden, Michaela Michel-Schuldt, Jane Sandall, Hora Soltani, Anna M Speciale, Jennifer Stevens, Saraswathi Vedam, Mary J Renfrew
Despite decades of considerable economic investment in improving the health of families and newborns world-wide, aspirations for maternal and newborn health have yet to be attained in many regions. The global turn toward recognizing the importance of positive experiences of pregnancy, intrapartum and postnatal care, and care in the first weeks of life, while continuing to work to minimize adverse outcomes, signals a critical change in the maternal and newborn health care conversation and research prioritization...
June 21, 2018: Birth
Zhi-Wang Wang, Xiao-Yan Fu, Xiao-Li Cheng, Xiao-Ying Bao, Xue-Feng Liu, Hai-Jing Duan
OBJECTIVES: To observe the preventive and therapeutic action of Yuyin Ruangan Granule (YRG, Traditional Chinese Medicine) in hepatic fibrosis rats model and its effect on transforming growth factor-β1 (TGF-β1) expression. METHODS: The Wistar rats were randomly divided into 6 group ( n =10), and the model of hepatic fibrosis rats was established by subcutaneous injected with carbon tetrachloride (CCL4), fed on high-fat diet and 20% ethanol for 6 weeks, to survey the effect and mechanism of YRG preventing hypatic fibrosis by detecting liver function (the activity of alanine aminotransferase(ALT), aspartate aminotransferase(AST), etc...
February 8, 2018: Chinese Journal of Applied Physiology
M Alasmari, M Bӧhlke, C Kelley, T Maher, A Pino-Figueroa
The pentane extract of the Peruvian plant, Lepidium meyenii (Maca), has been demonstrated to possess neuroprotective activity in previous in vitro and in vivo studies (Pino-Figueroa et al. in Ann N Y Acad Sci 1199:77-85, 2010; Pino-Figueroa et al. in Am J Neuroprot Neuroregener 3:87-92, 2011). This extract contains a number of macamides that may act on the endocannabinoid system (Pino-Figueroa et al. in Ann N Y Acad Sci 1199:77-85, 2010; Pino-Figueroa et al., 2011; Dini et al. in Food Chem 49:347-349, 1994)...
June 20, 2018: Molecular Neurobiology
Parimala Narne, Vimal Pandey, Prakash Babu Phanithi
Nitric oxide (NO) and hydrogen sulfide (H2 S) are the key gasotransmitters with an imperious role in the maintenance of cerebrovascular homeostasis. A decline in their levels contributes to endothelial dysfunction that portends ischemic stroke (IS) or cerebral ischemia/reperfusion (CI/R). Nevertheless, their exorbitant production during CI/R is associated with exacerbation of cerebrovascular injury in the post-stroke epoch. NO-producing nitric oxide synthases are implicated in IS pathology and their activity is regulated, inter alia, by various post-translational modifications and chromatin-based mechanisms...
June 20, 2018: Molecular Neurobiology
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