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Pharmacological Research: the Official Journal of the Italian Pharmacological Society

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https://www.readbyqxmd.com/read/28108363/endothelial-maintenance-in-health-and-disease-importance-of-sex-differences
#1
REVIEW
Neja Mudrovcic, Samsul Arefin, Amaryllis H Van Craenenbroeck, Karolina Kublickiene
The vascular endothelium has emerged as more than just an inert monolayer of cells lining the vascular bed. It represents the interface between the blood stream and vessel wall, and has a strategic role in regulating vascular homeostasis by the release of vasoactive substances. Endothelial dysfunction contributes to the development and progression of cardiovascular disease. Recognition of sex-specific factors implicated in endothelial cell biology is important for the identification of clinically relevant preventive and/or therapeutic strategies...
January 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28099883/beta2-adrenergic-signaling-affects-the-phenotype-of-human-cardiac-progenitor-cells-through-emt-modulation
#2
Francesca Pagano, Francesco Angelini, Camilla Siciliano, Julia Tasciotti, Giorgio Mangino, Elena De Falco, Roberto Carnevale, Sebastiano Sciarretta, Giacomo Frati, Isotta Chimenti
Human cardiac progenitor cells (CPCs) offer great promises to cardiac cell therapy for heart failure. Many in vivo studies have shown their therapeutic benefits, paving the way for clinical translation. The 3D model of cardiospheres (CSs) represents a unique niche-like in vitro microenvironment, which includes CPCs and supporting cells. CSs have been shown to form through a process mediated by epithelial-to-mesenchymal transition (EMT). β2-adrenergic signaling significantly affects stem/progenitor cells activation and mobilization in multiple tissues, and crosstalk between β2-adrenergic signaling and EMT processes has been reported...
January 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28099882/the-35-year-odyssey-of-beta-blockers-in-cirrhosis-any-gender-difference-in-sight
#3
REVIEW
Maria Antonella Burza, Hanns-Ulrich Marschall, Laura Napoleone, Antonio Molinaro
Cirrhosis is the end-stage of chronic liver disease and leads to the development of portal hypertension and its complications such as esophagogastric varices. Non-selective beta blockers (NSBB) are the keystone for the treatment of portal hypertension since the 1980s and, over the decades, several studies have confirmed their beneficial effect on the prevention of variceal (re)bleeding. Pharmacological studies showed effects of gender, sex hormones, oral contraceptives, and pregnancy on cytochrome P450 (CYPs) enzymes that metabolise NSBB, suggesting that gender differences might exist in the effect of NSBB...
January 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28093357/are-the-innate-and-adaptive-immune-systems-setting-hypertension-on-fire
#4
REVIEW
Gisele F Bomfim, Fernanda Luciano Rodrigues, Fernando S Carneiro
Hypertension is the most common chronic cardiovascular disease and is associated with several pathological states, being an important cause of morbidity and mortality around the world. Low-grade inflammation plays a key role in hypertension and the innate and adaptive immune systems seem to contribute to hypertension development and maintenance. Hypertension is associated with vascular inflammation, increased vascular cytokines levels and infiltration of immune cells in the vasculature, kidneys and heart. However, the mechanisms that trigger inflammation and immune system activation in hypertension are completely unknown...
January 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28089943/resveratrol-supplementation-and-plasma-adipokines-concentrations-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#5
REVIEW
Mohsen Mohammadi Sartang, Zohreh Mazloom, Zahra Sohrabi, Saeed Sherafatmanesh, Reza Barati Boldaji
The results of human clinical trials have revealed that the effects of resveratrol on adipokines are inconsistent. Our objective was to elucidate the role of resveratrol supplementation on adipokines through a systematic review and a meta-analysis of available randomized placebo-controlled trials (RCTs).(1) The search included PubMed-MEDLINE, SCOPUS and ISI web of sciences database till up to 6th November 2016. Weight mean differences (WMD)(2) were calculated for net changes in adipokines using fixed-effects or random-effects models; meta-regression analysis and publication bias were conducted in accordance with standard methods...
January 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28089942/targeting-egfr-t790m-mutation-in-nsclc-from-biology-to-evaluation-and-treatment
#6
Antonio Passaro, Elena Guerini-Rocco, Alessia Pochesci, Davide Vacirca, Gianluca Spitaleri, Chiara Matilde Catania, Alessandra Rappa, Massimo Barberis, Filippo de Marinis
The identification of EGFR mutations and their respectively tyrosine kinase inhibitors (TKIs), changed dramatically treatment and survival of patients with EGFR-positive lung cancer. Nowadays, different EGFR TKIs as afatinib, erlotinib and gefitinib are approved worldwide for the treatment of NSCLC harbouring EGFR mutations, in particular exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. In first-line setting, when comparing with platinum-based chemotherapy, these target drugs improves progression-free survival, response rate and quality of life...
January 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28087443/an-update-on-the-physiological-and-therapeutic-relevance-of-gpcr-oligomers
#7
REVIEW
Batoul Farran
The traditional view on GPCRs held that they function as single monomeric units composed of identical subunits. This notion was overturned by the discovery that GPCRs can form homo- and hetero-oligomers, some of which are obligatory, and can further assemble into receptor mosaics consisting of three or more protomers. Oligomerisation exerts significant impacts on receptor function and physiology, offering a platform for the diversification of receptor signalling, pharmacology, regulation, crosstalk, internalization and trafficking...
January 11, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28087444/the-mechanistic-role-of-chemically-diverse-metal-ions-in-the-induction-of-autophagy
#8
REVIEW
Sumit Sahni, Dong-Hun Bae, Patric Jansson, Des Richardson
Autophagy is an evolutionary conserved cellular catabolic degradation process in response to stress which involves lysosomal degradation of unnecessary or damaged organelles and misfolded proteins. This is primarily a pro-survival pathway providing the cell with essential nutrients during stressful conditions. There are number of essential metal ions, which are required for normal physiological functioning of cells. Studies have shown that autophagy can be regulated by cellular metal ion concentrations. On the other hand, autophagy is also shown to regulate intracellular levels of certain metal ions...
January 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28087442/hydrogen-sulfide-protects-against-endoplasmic-reticulum-stress-and-mitochondrial-injury-in-nucleus-pulposus-cells-and-ameliorates-intervertebral-disc-degeneration
#9
Daoliang Xu, Haiming Jin, Jianxia Wen, Jiaoxiang Chen, Deheng Chen, Ningyu Cai, Yongli Wang, Jianle Wang, Yu Chen, Xiaolei Zhang, Xiangyang Wang
It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1β, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1β-induced apoptosis in nucleus pulposus (NP) cells...
January 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28077300/pharmacological-strategies-to-target-oncogenic-kras-signaling-in-pancreatic-cancer
#10
REVIEW
Hsiao-Ching Chuang, Po-Hsien Huang, Samuel K Kulp, Ching-Shih Chen
The clear importance of mutated KRAS as a therapeutic target has driven the investigation of multiple approaches to inhibit oncogenic KRAS signaling at different molecular levels. However, no KRAS-targeted therapy has reached the clinic to date, which underlies the intrinsic difficulty in developing effective, direct inhibitors of KRAS. Thus, this article provides an overview of the history and recent progress in the development of pharmacological strategies to target oncogenic KRAS with small molecule agents...
January 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28077299/anaplastic-lymphoma-kinase-alk-inhibitors-in-the-treatment-of-alk-driven-lung-cancers
#11
REVIEW
Robert Roskoski
Anaplastic lymphoma kinase is expressed in two-thirds of the anaplastic large-cell lymphomas as an NPM-ALK fusion protein. Physiological ALK is a receptor protein-tyrosine kinase within the insulin receptor superfamily of proteins that participates in nervous system development. The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. The amino-terminal portions of the ALK fusion proteins result in dimerization and subsequent activation of the ALK protein kinase domain that plays a key role in the pathogenesis of various tumors...
January 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28082173/balancing-thromboembolic-and-bleeding-risk-with-non-vitamin-k-antagonist-oral-anticoagulants-noacs-a-systematic-review-and-meta-analysis-on-gender-differences
#12
REVIEW
Marco Proietti, Paola Cheli, Stefania Basili, Michal Mazurek, Gregory Y H Lip
Sex and gender differences have been reported in atrial fibrillation (AF), especially in relation to differences in thromboembolic and bleeding risks. More recently, pharmacological treatments have changed following the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) progressively replacing vitamin K antagonists (VKAs). The aims of this systematic review are to summarize the available evidence on NOACs and the relationship to major adverse outcomes according to sex. Moreover, we performed a meta-analysis of data from the phase III clinical trials investigating the sex effect on stroke/systemic embolic events (SEE) and major bleeding...
January 7, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28065857/downstream-regulatory-element-antagonist-modulator-dream-a-target-for-anti-thrombotic-agents
#13
Jaehyung Cho
Circulating platelets participate in the process of numerous diseases including thrombosis, inflammation, and cancer. Thus, it is of great importance to understand the underlying mechanisms mediating platelet activation under disease conditions. Emerging evidence indicates that despite the lack of a nucleus, platelets possess molecules that are involved in gene transcription in nucleated cells. This review will summarize downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, and highlight recent findings suggesting its novel non-transcriptional role in hemostasis and thrombosis...
January 5, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28063894/dysregulation-of-cytokine-mediated-chemotherapy-induced-cognitive-impairment
#14
REVIEW
Xiaojia Ren, Daret K St Clair, D Allan Butterfield
One of the major complaints patients who survive cancer often make is chemotherapy induced cognitive impairment (CICI), which survivors often call "chemo brain." CICI is a side effect of chemotherapy due to the cytotoxicity and neurotoxicity of anti-cancer drugs causing structural and functional changes in brain, even when drugs that do not cross the blood brain barrier (BBB) are used. Diminished cognitive functions including diminution of learning and memory, concentration and attention, processing speed and executive functions that reduce quality of life and ability to work are common signs and symptoms of CICI...
January 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28049048/vitamin-d-in-autoimmune-rheumatic-diseases-a-view-inside-gender-differences
#15
REVIEW
Massimiliano Vasile, Clarissa Corinaldesi, Cristina Antinozzi, Clara Crescioli
A large body of evidence highlights the role for vitamin D deficiency/insufficiency in rheumatic diseases, a group of different pathologies mostly of autoimmune origin. Vitamin D and vitamin D receptor agonists exquisitely modulate the immune system against over-reactivity towards tolerance; on this basis, vitamin D could be a good therapeutic candidate to control autoimmune processes in rheumatic diseases. Similarly, to other autoimmune pathologies, rheumatic diseases show a significant female bias. This sexual dimorphism seems, in part, to rely on the different sex hormone-induced regulation on male and female immune systems...
December 31, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28043879/-6-gingerol-and-6-shogaol-active-ingredients-of-the-traditional-japanese-medicine-hangeshashinto-relief-oral-ulcerative-mucositis-induced-pain-via-action-on-na-channels
#16
Suzuro Hitomi, Kentaro Ono, Kiyoshi Terawaki, Chinami Matsumoto, Keita Mizuno, Kiichiro Yamaguchi, Ryota Imai, Yuji Omiya, Tomohisa Hattori, Yoshio Kase, Kiyotoshi Inenaga
The traditional Japanese herbal medicine hangeshashinto (HST) has beneficial effects for the treatment of oral ulcerative mucositis (OUM) in cancer patients. However, the ingredient-based mechanism that underlies its pain-relieving activity remains unknown. In the present study, to clarify the analgesic mechanism of HST on OUM-induced pain, we investigated putative HST ingredients showing antagonistic effects on Na(+) channels in vitro and in vivo. A screen of 21 major ingredients using automated patch-clamp recordings in channel-expressing cells showed that [6]-gingerol and [6]-shogaol, two components of a Processed Ginger extract, considerably inhibited voltage-activated Na(+) currents...
December 30, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28042087/melatonin-as-a-promising-agent-of-regulating-stem-cell-biology-and-its-application-in-disease-therapy
#17
REVIEW
Shuo Zhang, Simon Chen, Yuan Li, Yu Liu
Stem cells have emerged as an important approach to repair and regenerate damaged tissues or organs and show great therapeutic potential in a variety of diseases. However, the low survival of engrafted stem cells still remains a major challenge for stem cell therapy. As a major hormone from the pineal gland, melatonin has been shown to play an important role in regulating the physiological and pathological functions of stem cells, such as promoting proliferation, migration and differentiation. Thus, melatonin combined with stem cell transplantation displayed promising application potential in neurodegenerative diseases, liver cirrhosis, wound healing, myocardial infarction, kidney ischemia injury, osteoporosis, etc...
December 30, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28042086/curcumin-a-potentially-powerful-tool-to-reverse-cisplatin-induced-toxicity
#18
REVIEW
Ramin Rezaee, Amir Abbas Momtazi, Alireza Monemi, Amirhossein Sahebkar
Curcumin is a naturally occurring polyphenol isolated from Curcuma longa that has gained considerable interest over the last decades due to its beneficial effects for human health. Moreover, the usage of cisplatin, a platinum-based chemotherapeutic, is associated with several adverse effects affecting the quality of life of the patients. Also, cisplatin therapy is jeopardized by a great challenge of resistance which reduces the efficacy of this drug. In order to conquer these dark sides of cisplatin therapy, curcumin has been widely used to fight against cisplatin-resistant cancer cells and decrease its unwanted side effects (e...
December 29, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28040533/tacrine-in-vivo-veritas
#19
Bevyn Jarrott
Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia...
December 28, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28027910/pharmacological-chaperone-approaches-for-rescuing-gpcr-mutants-current-state-challenges-and-screening-strategies
#20
Pieter Beerepoot, Reza Nazari, Ali Salahpour
A substantial number of G-protein coupled receptors (GPCRs) genetic disorders are due to mutations that cause misfolding or dysfunction of the receptor product. Pharmacological chaperoning approaches can rescue such mutant receptors by stabilizing protein conformations that behave similar to the wild type protein. For example, this can be achieved by improving folding efficiency and/or interaction with chaperone proteins. Although efficacy of pharmacological chaperones has been demonstrated in vitro for a variety of GPCRs, translation to clinical use has been limited...
December 24, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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