journal
Journals Journal of Pharmacology and Ex...

Journal of Pharmacology and Experimental Therapeutics

https://read.qxmd.com/read/38531640/-initial-characterization-of-a-transgenic-mouse-with-overexpression-of-the-human-h-1-histamine-receptor-on-the-heart
#1
JOURNAL ARTICLE
Lina Maria Rayo Abella, Hannes Jacob, Max Keller, Lisa Schindler, Steffen Pockes, Sebastian Pitzl, Jan Klimas, Katarina Hadova, Sarah Schneider, Igor B Buchwalow, CongYu Jin, Pertti Panula, Uwe Kirchhefer, Joachim Neumann, Ulrich Gergs
There is controversy whether H1 -histamine receptors increase or decrease contractility in the mammalian heart. Therefore, we have generated mice that overexpress the human H1 -histamine receptor in the heart (H1 -TG). We hypothesized that histamine would either increase or decrease force of contraction and beating rate compared to littermate wild type mice (WT). In H1 -TG mice, we ascertained the presence of H1 -histamine receptors by autoradiography of atrium and ventricle using [3 H]mepyramine. The messenger RNA for human H1 -histamine-receptors was present in cardiac samples from H1 -TG and absent from WT...
March 26, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38508753/-use-of-crispr-cas9-with-homology-directed-repair-hdr-to-gene-edit-topoisomerase-ii%C3%AE-in-human-leukemia-k562-cells-generation-of-a-resistance-phenotype
#2
JOURNAL ARTICLE
Jessika Carvajal-Moreno, Xinyi Wang, Victor A Hernandez, Milon Mondal, Xinyu Zhao, Jack C Yalowich, Terry S Elton
DNA topoisomerase IIβ (TOP2β/180; 180 kDa) is a nuclear enzyme that regulates DNA topology by generation of short-lived DNA double-strand breaks primarily during transcription. TOP2β/180 can be a target for DNA damage-stabilizing anticancer drugs, whose efficacy is often limited by chemoresistance. Our laboratory previously demonstrated reduced levels of TOP2β/180 (and the paralog TOP2α/170) in an acquired etoposide-resistant K562 clonal cell line, K/VP.5 in part due to overexpression of microRNA-9-3p/5p impacting post-transcriptional events...
March 20, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38508752/synaptic-plasticity-and-cognitive-ability-in-experimental-adult-onset-hypothyroidism
#3
JOURNAL ARTICLE
Karim A Alkadhi
Adult-onset hypothyroidism impairs normal brain function. Research on animal models of hypothyroidism has revealed critical information on how deficiency of thyroid hormones impacts the electrophysiological and molecular functions of the brain, which lead to the well-known cognitive impairment in untreated hypothyroid patients. Currently, such information can only be obtained from experiments on animal models of hypothyroidism. This review summarizes important research findings that pertain to understanding the clinical cognitive consequences of hypothyroidism, which will provide a guiding path for therapy of hypothyroidism...
March 20, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38458768/dosing-time-dependent-difference-in-the-suppressive-effect-of-empagliflozin-on-the-development-of-mechanical-pain-hypersensitivity-in-diabetic-mice
#4
JOURNAL ARTICLE
Ai Sato, Sai Yasukochi, Naho Iwanaka, Tomoaki Yamauchi, Akito Tsuruta, Satoru Koyanagi, Shigehiro Ohdo
A problem for patients with diabetes is the rise of complications, such as peripheral neuropathy, nephropathy and retinopathy. Among them, peripheral neuropathy, characterized by numbness and/or hypersensitivity to pain in the extremities, is likely to develop in the early stages of diabetes. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 inhibitor, exerts hypoglycemic effects by preventing glucose reabsorption in proximal tubular cells. EMPA can improve cardiovascular and renal outcomes in diabetic patients, but its suppressive effect on the development of diabetic neuropathy remains unclear...
March 8, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38453527/-research-progress-on-the-correlation-between-acetaldehyde-dehydrogenase-2-and-hepatocellular-carcinoma-development
#5
JOURNAL ARTICLE
Dashuai Yang, Ying Hu, Junfa Yang, Liangsong Tao, Yue Su, Yincui Wu, Yan Yao, Shuxian Wang, Sheng Ye, Tao Xu
Hepatocellular carcinoma (HCC) is the predominant pathological type of primary liver cancer. It is a malignant tumor of liver epithelial cells. There are many ways to treat HCC, but the survival rate for HCC patients remains low. Therefore, understanding the underlying mechanisms by which HCC occurs and develops is critical to explore new therapeutic targets. Aldehyde dehydrogenase 2 (ALDH2) is an important player in the redox reaction of ethanol with endogenous aldehyde products released by lipid peroxidation...
March 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38453526/-structure-activity-relationship-and-voltage-dependence-for-the-drug-drug-interaction-between-amiodarone-analogs-and-mni%C3%A2-1-at-the-l-type-cav-channel
#6
JOURNAL ARTICLE
Jixin Wang, Haoyu Zeng, Grace Dong, Sherman Waddell, John McCauley, Armando Lagrutta
The drug-drug interaction (DDI) between Amiodarone (AMIO) and Sofosbuvir (SOF), a direct-acting Hepatitis-C NS5B Nucleotide Polymerase Inhibitor, has been associated with severe bradyarrhythmia in patients. Recent Cryo-EM data has revealed that this DDI occurs at the α-subunit of L-type Cav channels (LTCC), with AMIO binding at the fenestration site and SOF (or MNI-1: analog of SOF) binding at the central cavity of the conductance pathway. In this study, we investigated the DDI between 21 AMIO analogs, including Dronedarone (DRON), and MNI-1 (or SOF) in hiPSC-CMs (human induced pluripotent stem cell-derived cardiomyocytes) and hCav1...
March 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38453525/-beclin-1-derived-peptide-mp1-attenuates-renal-fibrosis-by-inhibiting-the-wnt-%C3%AE-catenin-pathway
#7
JOURNAL ARTICLE
Jianfeng Zhang, Xiaocui Feng, Runling Yang, Jingya Bai, Feiyun Gao, Bangzhi Zhang
Renal fibrosis is distinguished by the abnormal deposition of extracellular matrix (ECM) and progressive loss of nephron function, with a lack of effective treatment options in clinical practice. In this study, we discovered that the Beclin-1-derived peptide MP1 significantly inhibits the abnormal expression of fibrosis and Epithelial-mesenchymal transition (EMT)-related markers, including α-Smooth muscle actin (α-SMA), Fibronectin (FN), Collagen I (Col I), Matrix metallopeptidase 2 (MMP2), Snail1, and Vimentin (Vim) both in vitro and in vivo...
March 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38453524/pharmacologic-characterization-of-substituted-nitazenes-at-mu-kappa-and-delta-opioid-receptors-suggests-high-potential-for-toxicity
#8
JOURNAL ARTICLE
Laura B Kozell, Amy J Eshleman, Katherine M Wolfrum, Tracy L Swanson, Shelley H Bloom, Sheila Benware, Jennifer L Schmachtenberg, Kamryn A Schutzer, William E Schutzer, Aaron Janowsky, Atheir I Abbas
The benzimidazole opioids (BO, substituted nitazenes) are highly potent MOR agonists with heroin- or fentanyl-like effects. These compounds have caused hospitalizations and fatal overdoses. We characterized the in vitro pharmacology and structure-activity relationships of 19 nitazenes with substitutions at three positions of the benzimidazole core. Affinities were assessed using agonist radioligand binding assays at human mu, kappa, and delta opioid receptors (MOR, KOR, and DOR, respectively) heterologously expressed in Chinese hamster ovary (CHO) cells...
March 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38453523/evidence-for-cytoprotective-autophagy-in-response-to-her2-targeted-monoclonal-antibodies
#9
JOURNAL ARTICLE
Ahmed M Elshazly, Aya A Elzahed, David A Gewirtz
The advent of HER2-targeted monoclonal antibodies such as trastuzumab has significantly improved the clinical outcomes for patients with breast cancer overexpressing HER2, and more recently also for gastric cancers. However, the development of resistance, as is frequently the case for other antineoplastic modalities, constrains clinical efficacy. Multiple molecular mechanisms and signaling pathways have been investigated for their potential involvement in the development of resistance to HER2-targeted therapies, among which is autophagy...
March 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38448247/-humanization-of-slco2b1-in-rats-increases-rcyp3a1-protein-expression-but-not-the-metabolism-of-erlotinib-to-osi-420
#10
JOURNAL ARTICLE
Marta Rysz, Anima M Schäfer, Nikolaos Paloumpis, Jonny Kinzi, Karin Brecht, Isabell Seibert, Seraina Schmidlin, Katja In-Albon, Daniel Ricklin, Henriette E Meyer Zu Schwabedissen
The organic anion transporting polypeptide (OATP) 2B1 (gene name SLCO2B1 ) is an uptake transporter that facilitates cellular accumulation of its substrates. In order to assess the in vivo relevance of the transporter, we applied SLCO2B1+/+ knock-in and Slco2b1-/- knock-out rats. A first pharmacological phenotyping with the OATP2B1 substrate-drug atorvastatin revealed reduced hepatic content and increased expression of rCYP3A1 in the humanized animals. It was the aim of this study to determine whether changes in metabolic activity affect the in vivo handling of the OATP2B1 and CYP3A1 substrate erlotinib, which is metabolized to OSI-420...
March 6, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38409115/-comparison-of-the-%C3%A2%C2%B5-opioid-receptor-antagonists-methocinnamox-mcam-and-naloxone-to-reverse-and-prevent-the-ventilatory-depressant-effects-of-fentanyl-carfentanil-3-methylfentanyl-and-heroin-in-male-rats
#11
JOURNAL ARTICLE
Takato Hiranita, Nicholas P Ho, Charles P France
The number of opioid overdose deaths has increased significantly over the past decade. The life-threatening effect of opioids is hypoventilation that can be reversed by the µ-opioid receptor (MOR) antagonist naloxone; however, because of the very short duration of action of naloxone, re-emergence of MOR agonist-induced hypoventilation can occur, requiring additional doses of naloxone. The MOR antagonist methocinnamox (MCAM) antagonizes hypoventilation by the non-morphinan fentanyl and the morphinan heroin in laboratory animals with an unusually long duration of action...
February 26, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38409114/development-of-cilofexor-an-intestinally-biased-farnesoid-x-receptor-agonist-for-the-treatment-of-fatty-liver-disease
#12
JOURNAL ARTICLE
David Hollenback, Eva Hambruch, Gero Fink, Manfred Birkel, Andreas Schulz, Martin Hornberger, Kathy Liu, Kelly MacLennan Staiger, Helen Desiree Krol, Ulrich Deuschle, Christoph Steeneck, Olaf Kinzel, John T Liles, Grant Budas, William J Watkins, Claus Kremoser
The farnesoid X receptor (FXR) is a nuclear receptor that controls bile acid, lipid, and cholesterol metabolism. FXR-targeted drugs have shown promise in late-stage clinical trials for non-alcoholic steatohepatitis. Herein, we used clinical results from our first non-steroidal FXR agonist, Px-102 (4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]cyclopropyl] benzoic acid), to develop cilofexor, a potent, non-steroidal FXR agonist with a more manageable safety profile. Px-102 demonstrated the anticipated pharmacodynamic (PD) effects in healthy volunteers but caused a 2-fold increase in alanine aminotransferase (ALT) activity and changes in cholesterol levels...
February 26, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38409113/-ncp-a-dual-kappa-and-mu-opioid-receptor-agonist-is-a-potent-analgesic-against-inflammatory-pain-without-reinforcing-or-aversive-properties
#13
JOURNAL ARTICLE
Peng Huang, Conrad K Ho, Danni Cao, Saadet Inan, Scott M Rawls, Mengchu Li, Boshi Huang, Piyusha P Pagare, E Andrew Townsend, Justin L Poklis, Matthew S Halquist, Matthew Banks, Yan Zhang, Lee-Yuan Liu-Chen
While agonists of mu (MOR) and kappa (KOR) opioid receptors have analgesic effects, they produce euphoria and dysphoria, respectively. Other side effects include respiratory depression and addiction for MOR agonists and sedation for KOR agonists. We reported that 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-{[4'-(2'-cyanopyridyl)]carboxamido}cmorphinan (NCP) displayed potent KOR full agonist and MOR partial agonist activities (58%) with 6.5x KOR-over-MOR selectivity in vitro Herein, we characterized pharmacological effects of NCP in rodents...
February 26, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38409112/-pharmacokinetics-of-panobinostat-inter-species-difference-in-metabolic-stability
#14
JOURNAL ARTICLE
Wenqiu Zhang, Ju-Hee Oh, Wenjuan Zhang, Courtney C Aldrich, Rachael W Sirianni, William F Elmquist
Panobinostat is a potent pan-HDAC inhibitor that has been tested in multiple studies for the treatment of brain tumors. There have been contrasting views surrounding its efficacy for the treatment of tumors in the CNS following systemic administration when examined in different models or species. We conducted experiments using three different mouse strains or genotypes to have a more comprehensive understanding of the systemic as well as the CNS distributional kinetics of panobinostat. Our study found that panobinostat experienced rapid degradation in vitro in FVB mouse matrices and a faster degradation rate was observed at 37{degree sign}C compared with room temperature and 4{degree sign}C, suggesting that the in vitro instability of panobinostat was due to enzymatic metabolism...
February 26, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38336381/-endothelial-extracellular-vesicles-enriched-in-microrna-34a-predict-new-onset-diabetes-in-covid-19-patients-novel-insights-for-long-covid-metabolic-sequelae
#15
JOURNAL ARTICLE
Pasquale Mone, Stanislovas S Jankauskas, Maria Virginia Manzi, Jessica Gambardella, Antonietta Coppola, Urna Kansakar, Raffaele Izzo, Giuseppe Fiorentino, Angela Lombardi, Fahimeh Varzideh, Daniela Sorriento, Bruno Trimarco, Gaetano Santulli
Emerging evidence indicates that the relationship between COVID-19 and diabetes is twofold: 1) it is known that the presence of diabetes and other metabolic alterations poses a considerably high risk to develop a severe COVID-19; 2) patients who survived a SARS-CoV-2 infection have an increased risk of developing new-onset diabetes. However the mechanisms underlying this association are mostly unknown and there are no reliable biomarkers to predict the development of new-onset diabetes. In the present study, we demonstrate that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts the risk of developing new-onset diabetes in COVID-19...
February 9, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38336380/-n-acetylcysteine-alters-disease-progression-and-increases-janus-kinase-mutation-frequency-in-a-mouse-model-of-precursor-b-cell-acute-lymphoblastic-leukemia
#16
JOURNAL ARTICLE
Mia P Sams, James Iansavitchous, Madeline Astridge, Heidi Rysan, Li S Xu, Bruno Rodrigues de Oliveira, Rodney P DeKoter
B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine (NAC) was tested for its ability to alter disease progression in a mouse model of B-ALL. Mb1-CreDPB mice have deletions in genes encoding PU.1 and Spi-B in B cells and develop B-ALL at 100% incidence. Treatment of Mb1-CreDPB mice with NAC in drinking water significantly reduced the frequency of CD19+ pre-B ALL cells infiltrating the thymus at 11 weeks of age...
February 9, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38336379/reversal-of-high-fat-diet-induced-obesity-systemic-inflammation-and-astrogliosis-by-the-nlrp3-inflammasome-inhibitors-nt-0249-and-nt-0796
#17
JOURNAL ARTICLE
Peter Thornton, Valérie Reader, Zsofia Digby, Pamela Smolak, Nicola Lindsay, David Harrison, Nick Clarke, Alan P Watt
Systemic and cerebral inflammatory responses are implicated in the pathogenesis of obesity and associated metabolic impairment. While the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to obesity-associated inflammation, whether it contributes to the development or maintenance of obesity is unknown. We provide support for a direct role of saturated fatty acids, such as palmitic acid, as NLRP3 activating stimuli in obese states. To investigate whether NLRP3 activation contributes to the pathogenesis of diet-induced obesity (DIO) in mice, we tested two different clinical-stage NLRP3 inflammasome inhibitors...
February 9, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38296646/-a-pilot-study-to-assess-the-suitability-of-riboflavin-as-a-surrogate-marker-of-breast-cancer-resistance-protein-bcrp-in-healthy-participants
#18
JOURNAL ARTICLE
Hong Shen, Runlan Huo, Yueping Zhang, Linna Wang, Nian Tong, Weiqi Chen, Andrew J Paris, Kofi Mensah, Min Chen, Yongjun Xue, Wenying Li, Michael Sinz
We recently showed that riboflavin is a selected substrate of BCRP over P-gp and demonstrated its prediction performance in preclinical DDI studies. The aim of this study was to investigate the suitability of riboflavin to assess BCRP inhibition in humans. First, we assessed the substrate potential of riboflavin towards other major drug transporters using established transfected cell systems. Riboflavin is a substrate for OAT1, OAT3, and MATE2-K with uptake ratios ranging from 2.69 to 11.6 but riboflavin is not a substrate of OATP1B1, OATP1B3, OCT2, and MATE1...
January 31, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38296645/-lucanthone-a-potential-ppt1-inhibitor-perturbs-stemness-reduces-tumor-microtube-formation-and-slows-the-growth-of-temozolomide-resistant-gliomas-in-vivo
#19
JOURNAL ARTICLE
Daniel P Radin, Sophie Shifman, Ian R Outhwaite, Aryan Sharma, Robert Bases, Markus A Seeliger, Stella E Tsirka
Glioblastoma (GBM) is the most frequently diagnosed primary CNS tumor in adults. Despite the standard of care therapy which includes surgical resection, temozolomide chemotherapy, radiation and the newly added tumor treating fields, median survival remains only ~20 months. Unfortunately, GBM has a ~100% recurrence rate, but after recurrence there are no FDA-approved therapies to limit tumor growth and enhance patient survival, as these tumors are resistant to TMZ. Recently, our laboratory reported that lucanthone slows GBM by inhibiting autophagic flux through lysosome targeting and decreases the number of Olig2+ glioma stem-like cells (GSC) in vitro and in vivo...
January 31, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38296644/chemotherapeutics-loaded-poly-dopamine-core-shell-nanoparticles-for-breast-cancer-treatment
#20
JOURNAL ARTICLE
Miranda Steeves, Diego Combita, William Whelan, Marya Ahmed
Chemophotothermal therapy is an emerging treatment for metastatic and drug resistant cancer anomalies. Among various photothermal agents tested, polydopamine provides an excellent biocompatible alternative that can be used to develop novel drug delivery carriers for cancer treatment. This study explores the synthesis of starch encapsulated, polydopamine coated core-shell nanoparticles, in a one pot synthesis approach and by surfactant free approach. The nanoparticles produced are embellished with polymeric stealth coatings and are tested for their physiological stability, photothermal properties, and drug delivery in metastatic triple negative breast cancer cell (TNBC) lines...
January 31, 2024: Journal of Pharmacology and Experimental Therapeutics
journal
journal
23880
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.