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Pharmacological Research: the Official Journal of the Italian Pharmacological Society

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https://www.readbyqxmd.com/read/29162539/modulation-of-diverse-oncogenic-transcription-factors-by-thymoquinone-an-essential-oil-compound-isolated-from-the-seeds-of-nigella-sativa-linn
#1
REVIEW
Muthu K Shanmugam, Frank Arfuso, Alan Prem Kumar, Lingzhi Wang, Boon Cher Goh, Kwang Seok Ahn, Anupam Bishayee, Gautam Sethi
Thymoquinone (TQ), isolated almost fifty years ago, is the main bioactive constituent of black seed essential oil extracted from the seed of Nigella sativa. TQ has been shown to have promising effects against a variety of inflammatory diseases and cancer. Cancer development is a multistep process where normal cells acquire qualities that enable the cells to proliferate continuously and migrate to distant sites in the human body. Drugs that interfere with this process are considered potential anti-cancer therapeutics, which may ultimately result in their clinical usage...
November 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29162538/metformin-promotes-the-proliferation-and-differentiation-of-murine-preosteoblast-by-regulating-the-expression-of-sirt6-and-oct4
#2
Wei Mu, Zhuoran Wang, Chuanyu Ma, Yunyun Jiang, Nannan Zhang, Kaiqiang Hu, Liyuan Li, Zhao Wang
Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin's effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast...
November 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29158049/down-regulation-of-pro-inflammatory-pathways-by-tanshinone-iia-and-cryptotanshinone-in-a-non-genetic-mouse-model-of-alzheimer-s-disease
#3
Francesco Maione, Marialuisa Piccolo, Simona De Vita, Maria Giovanna Chini, Claudia Cristiano, Carmen De Caro, Pellegrino Lippiello, Maria Concetta Miniaci, Rita Santamaria, Carlo Irace, Vincenzo De Feo, Antonio Calignano, Nicola Mascolo, Giuseppe Bifulco
Alzheimer's disease (AD) is a common form of dementia mainly characterized by the deposition of neurofibrillary tangles and β-amyloid (Aβ) peptides in the brain. Additionally, increasing evidence demonstrates that a neuro-inflammatory state plays a key role in the development of this disease. Beside synthetic drugs, the use of natural compounds represents an alternative for the development of new potential drugs for the treatment of AD. Among these, the root of Salvia miltiorhiza Bunge (also known as Danshen) used for the treatment of cardiovascular, cerebrovascular disease and CNS functional decline in Chinese traditional medicine is one of the most representative examples...
November 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29158048/enantiomer-specific-positive-allosteric-modulation-of-cb1-signaling-in-autaptic-hippocampal-neurons
#4
Jose Mitjavila, Danielle Yin, Pushkar M Kulkarni, Chiara Zanato, Ganesh A Thakur, Ruth Ross, Iain Greig, Ken Mackie, Alex Straiker
The cannabinoid signaling system is found throughout the CNS and its involvement in several pathological processes makes it an attractive therapeutic target. Because orthosteric CB1 cannabinoid receptor ligands have undesirable adverse effects there has been great interest in the development of allosteric modulators - both negative (NAMs) and positive (PAMs) - of these receptors. NAMs of CB1 appeared first on the scene, followed more recently by PAMs. Because allosteric modulation can vary depending on the orthosteric ligand it is important to study their function in a system that employs endogenous cannabinoids...
November 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29155256/role-of-toll-like-receptors-in-inflammatory-bowel-disease
#5
REVIEW
Nastaran Kordjazy, Arvin Haj-Mirzaian, Arya Haj-Mirzaian, Mohammad Mojtaba Rohani, Erwin W Gelfand, Nima Rezaei, Amir Hossein Abdolghaffari
Inflammatory bowel disease (IBD) is the chronic inflammation of the gastrointestinal tract. Recently, studies of the interplay between the adaptive and innate immune responses have provided a better understanding of the immunopathogenesis of inflammatory disorders such as IBD, as well as identification of novel targets for more potent interventions. Toll-like receptors (TLRs) are a class of proteins that play a significant role in the innate immune system and are involved in inflammatory processes. Activation of TLR signal transduction pathways lead to the induction of numerous genes that function in host defense, including those for inflammatory cytokines, chemokines, and antigen presenting molecules...
November 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29154989/targeting-bromodomain-and-extraterminal-proteins-in-breast-cancer
#6
REVIEW
Jennifer M Sahni, Ruth A Keri
Breast cancer is a collection of distinct tumor subtypes that are driven by unique gene expression profiles. These transcriptomes are controlled by various epigenetic marks that dictate which genes are expressed and suppressed. During carcinogenesis, extensive restructuring of the epigenome occurs, including aberrant acetylation, alteration of methylation patterns, and accumulation of epigenetic readers at oncogenes. As epigenetic alterations are reversible, epigenome-modulating drugs could provide a mechanism to silence numerous oncogenes simultaneously...
November 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29154988/role-of-p-mkk7-in-myricetin-induced-protection-against-intestinal-ischemia-reperfusion-injury
#7
Yuchao Sun, Mengqiao Lian, Yuan Lin, Bin Xu, Yanli Li, Jin Wen, Dapeng Chen, Ming Xu, Marwan Almoiliqy, Li Wang
Intestinal ischemia reperfusion (I/R) may cause inflammation-, oxidative stress-, and apoptosis-related tissue injuries and facilitate bacterial infection, leading to multiple organ failure. Myricetin, a flavonoid, is found to have diverse biological effects including anti-inflammatory, anti-oxidative, and anti-bacterial effects. Based on our pre-experiment, we proposed that myricetin pretreatment (25, 50mg/kg) could ameliorate intestinal I/R injury and myricetin-induced modulation on MKK7/JNK signal pathway might play a key role in the amelioration...
November 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29155017/p-glycoprotein-mdr1-abcb1-and-breast-cancer-resistance-protein-bcrp-abcg2-affect-brain-accumulation-and-intestinal-disposition-of-encorafenib-in-mice
#8
Jing Wang, Changpei Gan, Rolf W Sparidans, Els Wagenaar, Stéphanie van Hoppe, Jos H Beijnen, Alfred H Schinkel
Encorafenib (LGX818) is a promising BRAF(V600E) inhibitor that has efficacy against metastatic melanoma. To better understand its pharmacokinetics, we studied its interactions with the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug metabolizing enzyme CYP3A. In polarized MDCK-II cells, encorafenib was efficiently transported by canine and human ABCB1 and ABCG2 and by mouse Abcg2. Upon oral administration to wild-type, Abcb1a/1b(-/-), Abcg2(-/-), and Abcb1a/1b;Abcg2(-/-) mice, encorafenib was absorbed very quickly and to very high plasma levels, but without clear changes in oral availability between the strains...
November 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29155016/topical-administration-of-reversible-sahh-inhibitor-ameliorates-imiquimod-induced-psoriasis-like-skin-lesions-in-mice-via-suppression-of-tnf-%C3%AE-ifn-%C3%AE-induced-inflammatory-response-in-keratinocytes-and-t-cell-derived-il-17
#9
Ze-Min Lin, Meng Ma, Heng Li, Qing Qi, Yu-Ting Liu, Yu-Xi Yan, Yun-Fu Shen, Xiao-Qian Yang, Feng-Hua Zhu, Shi-Jun He, Wei Tang, Jian-Ping Zuo
DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. The present study was designed to characterize the potential therapeutic effects of DZ2002 on murine model of psoriasis and reveal the correlated mechanisms. In this report, we demonstrated that in vitro, DZ2002 significantly decreased the expression of pro-inflammatory cytokines and adhesion molecule including IL-1α, IL-1β, IL-6, IL-8, TNF-α and ICAM-1 by inhibiting the phosphorylation of p38 MAPK, ERK and JNK in TNF-α/IFN-γ-stimulated HaCaT human keratinocytes...
November 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29155015/optimized-lentiviral-transduction-of-human-amniotic-mesenchimal-stromal-cells
#10
Federica Pisano, Manuela Mura, Maria Chiara Ciuffreda, Federica Calabrò, Nicola Lanzo, Massimiliano Gnecchi
Mesenchymal stromal cells are excellent candidates for regenerative medicine since they are multipotent, easy to isolate, can be expanded to obtain clinically relevant numbers and they are immunoprivileged. Stable genetic modification with viral vectors can improve mesenchymal stromal cell function and enhance their therapeutic potential. However, standard viral vectors achieve sub-optimal transduction efficiency with a single infection. On the other hand, multiple transduction cycles or antibiotic-based selection methods may alter the stem cell phenotype...
November 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29155014/resveratrol-dimer-trans-%C3%AE%C2%B5-viniferin-prevents-rotaviral-diarrhea-in-mice-by-inhibition-of-the-intestinal-calcium-activated-chloride-channel
#11
Bo Yu, Yu Jiang, Bo Zhang, Hong Yang, Tonghui Ma
We previously identified, by a natural-product screen, resveratrol oligomers as inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Here, we report the resveratrol dimer trans-ε-viniferin (TV) and tetramer r-2-viniferin (RV) as inhibitors of the intestinal calcium-activated chloride channel (CaCC) and demonstrate their antisecretory efficacy in a neonatal mouse model of rotaviral diarrhea. Short-circuit measurements show inhibition of CaCC current in the human colonic cell line HT-29 by TV and RV with IC50∼1 and 20μM, respectively...
November 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29146209/the-blood-brain-barrier-and-braf-inhibitors-implications-for-patients-with-melanoma-brain-metastases
#12
EDITORIAL
Keiran S M Smalley, Peter A Forsyth
No abstract text is available yet for this article.
November 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29133216/anti-cancer-effects-of-naturally-derived-compounds-targeting-histone-deacetylase-6-related-pathways
#13
REVIEW
Manon Lernoux, Michael Schnekenburger, Mario Dicato, Marc Diederich
Alterations of the epigenetic machinery, affecting multiple biological functions, represent a major hallmark enabling the development of tumors. Among epigenetic regulatory proteins, histone deacetylase (HDAC)6 has emerged as an interesting potential therapeutic target towards a variety of diseases including cancer. Accordingly, this isoenzyme regulates many vital cellular regulatory processes and pathways essential to physiological homeostasis, as well as tumor multistep transformation involving initiation, promotion, progression and metastasis...
November 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29133215/myocardial-infarction-and-gut-microbiota-an-incidental-connection
#14
REVIEW
Sepideh Zununi Vahed, Abolfazl Barzegari, Marisol Zuluaga, Didier Letourneur, Graciela Pavon-Djavid
Myocardial infarction (MI) is the main cause of cardiovascular crises that entails serious concerns in mortality, morbidity, and cost to the society. The main therapeutic goal of modern cardiology is to develop novel approaches to minimize inflammation, myocardial necrosis/apoptosis, and enhance cardiac repair after MI. Though MI can be affected by genetic and environmental factors, the search for targeting lifestyle factors has been of greater interest. One such potential factor is the microbiota, the human intestinal microbial community...
November 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29133214/antibacterial-activity-and-pharmacokinetic-profile-of-a-promising-antibacterial-agent-14-o-4-amino-6-hydroxy-pyrimidine-2-yl-thioacetyl-mutilin
#15
Ruofeng Shang, Yunpeng Yi, Chao Zhang, Yunxing Fu, Jianping Liang, Wanxia Pu
A new pleuromutilin derivative, 14-O-[(4-Amino-6-hydroxy-pyrimidine-2-yl)thioacetyl] mutilin (APTM), has been synthesized and proved most potent antibacterial agent in in vitro assays, suggesting that further development of this compound may lead to a promising antibacterial drug. In this study, we further evaluated the cytotoxicity, antibacterial efficacy and the pharmacokinetic profile of APTM. In BRL 3A cells, 50% of viability was obtained when 363μg/mL of APTM was used, while retapamulin and tiamulin fumarate needed 49 and 28μg/mL, respectively, to reach this viability...
November 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29133213/long-noncoding-rnas-act-as-regulators-of-autophagy-in-cancer
#16
REVIEW
Ting Sun
Long noncoding RNAs (lncRNAs) have emerged as critical regulators in various cellular processes. Studies have disclosed an important function of lncRNAs in the regulation of autophagy, a crucial cellular homeostatic mechanism that plays a pro-survival or pro-death role in cancer. Deregulation of lncRNAs can contribute to tumorigenesis and cancer progression, wherein lncRNAs can act as oncogenes or tumor suppressors. In this review, we highlight the recent advances in understanding the relationship between lncRNAs and autophagy regulation in cancer...
November 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29133212/quantitative-and-systems-pharmacology-2-in-silico-polypharmacology-of-g-protein-coupled-receptor-ligands-via-network-based-approaches
#17
Zengrui Wu, Weiqiang Lu, Weiwei Yu, Tianduanyi Wang, Weihua Li, Guixia Liu, Hankun Zhang, Xiufeng Pang, Jin Huang, Mingyao Liu, Feixiong Cheng, Yun Tang
G protein-coupled receptors (GPCRs) are the largest super family with more than 800 membrane receptors. Currently, over 30% of the approved drugs target human GPCRs. However, only approximately 30 human GPCRs have been resolved three-dimensional crystal structures, which limits traditional structure-based drug discovery. Recent advances in network-based systems pharmacology approaches have demonstrated powerful strategies for identifying new targets of GPCR ligands. In this study, we proposed a network-based systems pharmacology framework for comprehensive identification of new drug-target interactions on GPCRs...
November 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29129670/microalgae-derived-oxylipins-decrease-inflammatory-mediators-by-regulating-the-subcellular-location-of-nf%C3%AE%C2%BAb-and-ppar-%C3%AE
#18
Javier Ávila-Román, Elena Talero, Carolina de Los Reyes, Sofía García-Mauriño, Virginia Motilva
Oxylipins (OXLs) are bioactive molecules generated by the oxidation of fatty acids that promote the resolution of acute inflammation and prevent chronic inflammatory processes through molecular mechanisms that are not well known. We have previously reported the anti-inflammatory activity of microalgae-derived OXLs and OXL-containing biomass in two inflammatory bowel disease (IBD) models: 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis and TNBS-induced recurrent colitis. In this study, we examined the in vitro anti-inflammatory mechanism of action of the most abundant OXLs isolated from Chlamydomonas debaryana (13S-HOTE and 13S-HODE) and Nannochloropsis gaditana (15S-HEPE)...
November 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29127059/hypertension-and-cardiovascular-risk-general-aspects
#19
REVIEW
Sverre E Kjeldsen
Hypertension is the strongest or one of the strongest risk factors for almost all different cardiovascular diseases acquired during life, including coronary disease, left ventricular hypertrophy and valvular heart diseases, cardiac arrhythmias including atrial fibrillation, cerebral stroke and renal failure. The continuous relationship between blood pressure and cardiovascular and renal events makes the distinction between high normal blood pressure and hypertension based on arbitrary cut-off values for blood pressures...
November 7, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29122696/es2-enhances-the-efficacy-of-chemotherapeutic-agents-in-abcb1-overexpressing-cancer-cells-in-vitro-and-in-vivo
#20
Yanfen Fang, Juanjuan Sun, Xing Zhong, Rui Hu, Jie Gao, Guanfu Duan, Changge Ji, Lijuan Chen, Wanli Zhang, Chunxiao Miao, Haji Akber Aisa, Xiongwen Zhang
ES2 is a new type of jatrophane diterpenoid ester isolated from the fructus E. sororia, a traditional Uyghur medicine in China. Here we reported the multidrug resistance (MDR) reversal effect of ES2 in vitro and in vivo by modulating the function of ATP-binding cassette subfamily B member 1 (ABCB1). ES2 exhibited low cytotoxicity to ABCB1-overexpressing MDR cells and their parental sensitive cells, but sensitized the MDR cells and ABCB1-transfected HEK293 cells to chemotherapeutic drugs that are ABCB1 substrates...
November 7, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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