Low-activity programming of the PDGFR β/FAK pathway mediates H-type vessel dysplasia and high susceptibility to osteoporosis in female offspring rats after prenatal dexamethasone exposure.
This study enhances the understanding of the molecular mechanism of dexamethasone-induced bone development toxicity and provides new insights for exploring the early intervention and therapeutic targets of foetal-derived osteoporosis. PMID: 33434537 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - January 9, 2021 Category: Drugs & Pharmacology Authors: Shangguan Y, Wu Z, Xie X, Zhou S, He H, Xiao H, Liu L, Zhu J, Chen H, Han H, Wang H, Chen L Tags: Biochem Pharmacol Source Type: research

Pharmacokinetics of metformin in collagen-induced arthritis rats.
In conclusion, our study suggested that the reduced bioavailability of metformin in CIA rats is possibly related to the up-regulated function of the renal protein OCT2. PMID: 33434538 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - January 9, 2021 Category: Drugs & Pharmacology Authors: Chen M, You G, Xie C, Yang R, Hu W, Zheng Z, Liu S, Ye L Tags: Biochem Pharmacol Source Type: research

Flavonoid display ability to target microRNAs in cancer pathogenesis.
Abstract MicroRNAs (miRNAs) are non-coding, conserved, single-stranded nucleotide sequences involved in physiological and developmental processes. Recent evidence suggests an association between miRNAs' deregulation with initiation, promotion, progression, and drug resistance in cancer cells. Besides, miRNAs are known to regulate the epithelial-mesenchymal transition, angiogenesis, autophagy, and senescence in different cancer types. Previous reports proposed that apart from the antioxidant potential, flavonoids play an essential role in miRNA modulation associated with changes in cancer-related proteins, tumor su...
Source: Biochemical Pharmacology - January 8, 2021 Category: Drugs & Pharmacology Authors: Singh S, Raza W, Parveen S, Meena A, Luqman S Tags: Biochem Pharmacol Source Type: research

Sulfasalazine alleviates neuropathic pain hypersensitivity in mice through inhibition of SGK-1 in the spinal cord.
Abstract Diurnal variations in pain hypersensitivity are common in chronic pain disorders. Temporal exacerbation of neuropathic pain hypersensitivity is dependent on diurnal variations in glucocorticoid secretion from the adrenal glands. We previously demonstrated that spinal expression of serum- and glucocorticoid-inducible kinase-1 (SGK-1) is associated with glucocorticoid- induced exacerbation of pain hypersensitivity, but there are no available strategies to inhibit SGK-1 in the spinal cord. By screening a clinically approved drug library (more than 1,200 drugs), we found that sulfasalazine (SSZ) has inhibitor...
Source: Biochemical Pharmacology - January 8, 2021 Category: Drugs & Pharmacology Authors: Yasukochi S, Kusunose N, Matsunaga N, Koyanagi S, Ohdo S Tags: Biochem Pharmacol Source Type: research

A switch in mechanism of action prevents doxorubicin-mediated cardiac damage.
Abstract Cancer patients treated with doxorubicin are at risk of congestive heart failure due to doxorubicin-mediated cardiotoxicity via topoisomerase IIβ poisoning. Acute cardiac muscle damage occurs in response to the very first dose of doxorubicin, however, cardioprotection has been reported after co-treatment of doxorubicin with acyloxyalkyl ester prodrugs. The aim of this study was to examine the role played by various forms of acute cardiac damage mediated by doxorubicin and determine a mechanism for the cardioprotective effect of formaldehyde-releasing prodrug AN-9 (pivaloyloxymethyl butyrate). Doxorub...
Source: Biochemical Pharmacology - January 8, 2021 Category: Drugs & Pharmacology Authors: Cheong A, McGrath S, Robinson T, Maliki R, Spurling A, Lock P, Rephaeli A, Nudelman A, Parker BS, Pepe S, Cutts SM Tags: Biochem Pharmacol Source Type: research

Regulation of p53 stability as a therapeutic strategy for cancer.
Abstract The tumor suppressor protein p53 participates in the control of key biological functions such as cell death, metabolic homeostasis and immune function, which are closely related to various diseases such as tumors, metabolic disorders, infection and neurodegeneration. The p53 gene is also mutated in approximately 50% of human cancer cells. Mutant p53 proteins escape from the ubiquitination-dependent degradation, gain oncogenic function and promote the carcinogenesis, malignant progression, metastasis and chemoresistance. Therefore, the stability of both wild type and mutant p53 needs to be precisely regula...
Source: Biochemical Pharmacology - January 6, 2021 Category: Drugs & Pharmacology Authors: Xu Z, Wu W, Yan H, Hu Y, He Q, Luo P Tags: Biochem Pharmacol Source Type: research

Modulation of recognition memory performance by light and its relationship with cortical EEG theta and gamma activities.
We report a light-intensity-dependent disruptive effect on recognition memory performance at the group level, but inspection of individual-level data indicates that light-intensity-dependent facilitation is observed in some cases. Using linear mixed-effects models, we then demonstrate that EEG fast theta (θ) activity at the time of encoding negatively predicts recognition memory performance, whereas slow gamma (γ) activity at the time of retrieval positively predicts performance. These relationships between θ/γ activity and performance are strengthened by increasing light intensity. Thus, light modu...
Source: Biochemical Pharmacology - January 4, 2021 Category: Drugs & Pharmacology Authors: Hasan S, Tam SKE, Foster RG, Vyazovskiy VV, Bannerman DM, Peirson SN Tags: Biochem Pharmacol Source Type: research

P2Y Receptors for Extracellular Nucleotides: Contributions to Cancer Progression and Therapeutic Implications.
an GA Abstract Purinergic receptors for extracellular nucleotides and nucleosides contribute to a vast array of cellular and tissue functions, including cell proliferation, intracellular and transmembrane ion flux, immunomodulation and thrombosis. In mammals, the purinergic receptor system is composed of G protein-coupled P1 receptors A1, A2A, A2B and A3 for extracellular adenosine, P2X1-7 receptors that are ATP-gated ion channels and G protein-coupled P2Y1,2,4,6,11,12,13 and 14 receptors for extracellular ATP, ADP, UTP, UDP and/or UDP-glucose. Recent studies have implicated specific P2Y receptor subtypes in numer...
Source: Biochemical Pharmacology - January 4, 2021 Category: Drugs & Pharmacology Authors: Woods LT, Muñoz Forti K, Shanbhag VC, Camden JM, Weisman GA Tags: Biochem Pharmacol Source Type: research

Purinergic signalling in host innate immune defence against intracellular pathogens.
Abstract Purinergic signalling is an evolutionarily conserved signalling pathway mediated by extracellular nucleotides and nucleosides. Tri- and diphosphonucleotides released from host cells during intracellular pathogen infections activate plasma membrane purinergic type 2 receptors (P2 receptors) that stimulate microbicidal mechanisms in host innate immune cells. P2X ion channels and P2Y G protein-coupled receptors are involved in activating host innate immune defence mechanisms, phagocytosis, phagolysosomal fusion, production of reactive species, acidification of parasitophorous vacuoles, inflammasome activatio...
Source: Biochemical Pharmacology - January 3, 2021 Category: Drugs & Pharmacology Authors: Coutinho-Silva R, Eduardo Baggio Savio L Tags: Biochem Pharmacol Source Type: research

Nanobodies as probes to investigate purinergic signaling.
e F Abstract Nanobodies (VHHs) are the single variable immunoglobulin domains of heavy chain antibodies (hcAbs) that naturally occur in alpacas and other camelids. The two variable domains of conventional antibodies typically interact via a hydrophobic interface. In contrast, the corresponding surface area of nanobodies is hydrophilic, rendering these single immunoglobulin domains highly soluble, robust to harsh environments, and exceptionally easy to format into bispecific reagents. In homage to Geoffrey Burnstock, the pioneer of purinergic signaling, we provide a brief history of nanobody-mediated modulation of ...
Source: Biochemical Pharmacology - December 31, 2020 Category: Drugs & Pharmacology Authors: Eggers M, Rühl F, Haag F, Koch-Nolte F Tags: Biochem Pharmacol Source Type: research

Chlorpromazine, an antipsychotic agent, induces G2/M phase arrest and apoptosis via regulation of the PI3K/AKT/mTOR-mediated autophagy pathways in human oral cancer.
In this study, treatment of human oral cancer cells with CPZ inhibited their proliferation and induced G2/M phase arrest. Treatment with CPZ induced apoptosis through the extrinsic death receptor and the intrinsic mitochondrial pathways. In addition, the induction of autophagy was observed by the formation of autophagosomes, the expression of autophagy-related proteins and activation of the PI3K/Akt/mTOR/p70S6K pathway. The CPZ-induced cell death was reversed by the pan-caspase inhibitor Z-VAD-FMK, by the autophagy inhibitor 3-MA and by the knockdown of LC3B using a shRNA (shLC3B), suggesting that autophagy promoted CPZ-in...
Source: Biochemical Pharmacology - December 31, 2020 Category: Drugs & Pharmacology Authors: Jhou AJ, Chang HC, Hung CC, Lin HC, Lee YC, Liu WT, Han KF, Lai YW, Lin MY, Lee CH Tags: Biochem Pharmacol Source Type: research

Comparative metabolomics reveals key pathways associated with the synergistic activity of polymyxin B and rifampicin combination against multidrug-resistant Acinetobacter baumannii.
This study is the first to reveal the synergistic killing mechanism of the polymyxin-rifampicin combination against polymyxin-susceptible MDR A. baumannii at the network level. Our findings provide new mechanistic insights for optimizing this synergistic combination in patients. PMID: 33387481 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 30, 2020 Category: Drugs & Pharmacology Authors: Zhao J, Han ML, Zhu Y, Lin YW, Wang YW, Lu J, Hu Y, Tony Zhou Q, Velkov T, Li J Tags: Biochem Pharmacol Source Type: research

The N6-methyladenosine modification posttranscriptionally regulates hepatic UGT2B7 expression.
In conclusion, this study clarified that RNA methylation posttranscriptionally controls hepatic UGT2B7 expression. PMID: 33387482 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 30, 2020 Category: Drugs & Pharmacology Authors: Ondo K, Isono M, Nakano M, Hashiba S, Fukami T, Nakajima M Tags: Biochem Pharmacol Source Type: research

Imperatorin ameliorates mast cell-mediated allergic airway inflammation by inhibiting MRGPRX2 and CamKII/ERK signaling pathway.
In this study, we focused on the therapeutical mechanism of IMP on MRGPRX2-induced pseudo-allergy and allergic asthma. METHODS: We examined the effect of IMP on MRGPRX2 related mast cell activation in mouse peritoneal MC (MPMC), Human Laboratory of Allergic Disease 2 MCs (LAD2 cells) and Mrgprx2-expressing HEK293 cells. Molecular docking and Surface plasmon resonance (SPR) were taken to reveal the binding character between IMP and MRPGRX2. MRGPRX2 downstream proteins were also detected by western blotting. IgE-independent responses was evaluated by using passive cutaneous anaphylaxis (PCA) and active systemic anaphyla...
Source: Biochemical Pharmacology - December 30, 2020 Category: Drugs & Pharmacology Authors: Wang N, Wang J, Zhang Y, Zeng Y, Hu S, Bai H, Hou Y, Wang C, He H, He L Tags: Biochem Pharmacol Source Type: research

Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgery in rabbits by suppressing canonical and non-canonical TGF β signaling through PPARα.
Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgery in rabbits by suppressing canonical and non-canonical TGFβ signaling through PPARα. Biochem Pharmacol. 2020 Dec 29;:114398 Authors: Li Y, Zhao S, Xu S, Li Y, Wang C, Ren J, Li F, Hu X, Lin K, Qiu Y, Xiu Y Abstract Postoperative adhesions and scarring are the particular complication after strabismus surgery, for which there is currently no comprehensive treatment available. Preventing inflammation and fibrosis in the extraocular muscle are crucial for treatment of postoperative adhesions. In the...
Source: Biochemical Pharmacology - December 29, 2020 Category: Drugs & Pharmacology Authors: Li Y, Zhao S, Xu S, Li Y, Wang C, Ren J, Li F, Hu X, Lin K, Qiu Y, Xiu Y Tags: Biochem Pharmacol Source Type: research

Purinergic signaling in diabetes and metabolism.
Abstract Purinergic signaling, a concept originally formulated by the late Geoffrey Burnstock (1929-2020), was found to modulate pathways in every physiological system. In metabolic disorders there is a role for both adenosine receptors and P2 (nucleotide) receptors, of which there are two classes, i.e. P2Y metabotropic and P2X ionotropic receptors. The individual roles of the 19 receptors encompassed by this family have been dissected - and in many cases the effects associated with specific cell types, including adipocytes, skeletal muscle, liver cells and immune cells. It is suggested that ligands selective for ...
Source: Biochemical Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: Jain S, Jacobson KA Tags: Biochem Pharmacol Source Type: research

S100A16 induces epithelial-mesenchymal transition in human PDAC cells and is a new therapeutic target for pancreatic cancer treatment that synergizes with gemcitabine.
In conclusion, our findings suggest that S100A16 is a novel potential therapeutic target for human PDAC treatment. PMID: 33359364 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: Li T, Ren T, Huang C, Li Y, Yang P, Che G, Luo L, Chen Y, Peng S, Lin Y, Zeng L Tags: Biochem Pharmacol Source Type: research

Single bioengineered ncRNA molecule for dual-targeting toward the control of non-small cell lung cancer patient-derived xenograft tumor growth.
In this study, we aimed at simultaneously introducing two miRNAs into NSCLC cells by using single recombinant "combinatorial BERA" (CO-BERA) molecule. Our studies show that single CO-BERA molecule (e.g., let-7c/miR-124) was successfully processed to two miRNAs (e.g., let-7c-5p and miR-124-3p) to combinatorially regulate the expression of multiple targets (e.g., RAS, VAMP3 and CDK6) in human NSCLC cells, exhibiting greater efficacy than respective BERA miRNAs in the inhibition of cell viability and colony formation. Furthermore, we demonstrate that CO-BERA let-7c/miR-124-loaded lipopolyplex nanomedicine was the mo...
Source: Biochemical Pharmacology - December 23, 2020 Category: Drugs & Pharmacology Authors: Petrek H, Yan Ho P, Batra N, Tu MJ, Zhang Q, Qiu JX, Yu AM Tags: Biochem Pharmacol Source Type: research

Purinergic signalling in the kidney: physiology and disease.
Abstract Historically, the control of renal vascular and tubular function has, for the most part, concentrated on neural and endocrine regulation. However, in addition to these extrinsic factors, it is now appreciated that several complex humoral control systems exist within the kidney that can act in an autocrine and/or paracrine fashion. These paracrine systems complement neuroendocrine regulation by dynamically tuning renal vascular and tubular function to buffer rapid changes in nephron perfusion and flow rate of tubular fluid. One of the most pervasive is the extracellular nucleotide/P2 receptor system, which...
Source: Biochemical Pharmacology - December 22, 2020 Category: Drugs & Pharmacology Authors: Monaghan MT, Bailey MA, Unwin RJ Tags: Biochem Pharmacol Source Type: research

Suppression MGP inhibits tumor proliferation and reverses oxaliplatin-resistance in colorectal cancer.
Abstract Matrix Gla protein (MGP), an extracellular matrix protein, has been widely reported to participate in the tumorigenic process and is abnormally expressed in several tumors. However, the role of MGP in colorectal cancer (CRC) remains unknown. Chemotherapy resistance represents a significant limitation in the treatment of CRC. Here, a comprehensive bioinformatics analysis revealed that MGP, which is overexpressed in CRC, might act as one of the critical genes conferring resistance to oxaliplatin (OXA). Furthermore, we found that MGP overexpression in tumor tissue might be correlated with cancer stage and pa...
Source: Biochemical Pharmacology - December 22, 2020 Category: Drugs & Pharmacology Authors: Huang C, Wang M, Wang J, Wu D, Gao Y, Huang K, Yao X Tags: Biochem Pharmacol Source Type: research

Negative correlation of urinary miR-199a-3p level with ameliorating effects of sarpogrelate and cilostazol in hypertensive diabetic nephropathy.
In this study, we aimed to identify urinary miRNAs reflecting the effect of therapeutic intervention in rats with comorbid hypertension and diabetes. Additionally, the potential beneficial effects of anti-platelet sarpogrelate and cilostazol were investigated. Nephropathy progression in streptozotocin (STZ)-treated spontaneously hypertensive rats (SHRs), including albuminuria, collagen deposition, and histopathological changes, was alleviated by sarpogrelate and antihypertensive agent telmisartan. Global analysis of urinary miRNAs identified that miR-199a-3p was commonly reduced by sarpogrelate and telmisartan treatment. I...
Source: Biochemical Pharmacology - December 22, 2020 Category: Drugs & Pharmacology Authors: Ki Kim S, Kim G, Choi BH, Ryu D, Ku SK, Kwak MK Tags: Biochem Pharmacol Source Type: research

Progress in modelling of brain dynamics during anaesthesia and the role of sleep-wake circuitry.
Abstract General anaesthesia is used widely in surgery and during interventional medical procedures, but little is known about the exact neural mechanisms for how unconsciousness arises from administering an anaesthetic drug. Computational modelling of brain dynamics has already provided valuable insights into the neural circuitry involved in generating this state. Current theories for the origin of electroencephalographic (EEG) features in brain activity under GABAergic anaesthetic drugs (e.g. propofol) have been proposed through modelling results. While much attention has been paid to describing alpha and delta ...
Source: Biochemical Pharmacology - December 21, 2020 Category: Drugs & Pharmacology Authors: Nguyen G, Postnova S Tags: Biochem Pharmacol Source Type: research

Purinergic receptors in airway hydration.
Abstract Airway epithelial purinergic receptors control key components of the mucociliary clearance (MCC), the dominant component of pulmonary host defense. In healthy airways, the periciliary liquid (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. When the hydration of the airway surface decreases, the mucus becomes hyperconcentrated, the PCL collapses, and the "thickened" mucus layer adheres to cell surfaces, causing plaque/plug formation. Mucus accumulation is a major contributing factor to the progression of chronic obstructiv...
Source: Biochemical Pharmacology - December 21, 2020 Category: Drugs & Pharmacology Authors: Lazarowski ER, Boucher RC Tags: Biochem Pharmacol Source Type: research

Prolonged cultured human hepatocytes as an in vitro experimental system for the evaluation of potency and duration of activity of RNA therapeutics: Demonstration of prolonged duration of gene silencing effects of a GalNAc-conjugated human hypoxanthine phosphoribosyl transferase (HPRT1) siRNA.
We report here the evaluation of a novel in vitro experimental model, prolonged cultured human hepatocytes (PCHC), as an experimental system to evaluate the potency and duration of effects of oligonucleotide therapeutics. A novel observation was made on the redifferentiation of PCHC upon prolonged culturing based on mRNA profiling of characteristic hepatic differentiation marker genes albumin, transferrin, and transthyretin. Consistent with the known de-differentiation of cultured human hepatocytes, decreases in marker gene expression were observed upon culturing of the hepatocytes for 2 days. A novel observation of re-dif...
Source: Biochemical Pharmacology - December 21, 2020 Category: Drugs & Pharmacology Authors: Yang Q, Humphreys SC, Lade JM, Li AP Tags: Biochem Pharmacol Source Type: research

The neurobiological underpinning of the circadian wake signal.
Abstract The circadian wake drive is a mathematic representation of the observed increased propensity to stay awake late in the day, peaking in the hours just before anticipated bed time. It has been called the "forbidden zone" due to the difficulty in initiating sleep during this time and is responsible for the problems initiating sleep when traveling eastward, for maintaining daytime sleep in shift workers, and for initiating sleep in some individuals with insomnia. Evidence culled from studies in individuals with narcolepsy, who lack production of hypocretin (orexin) neuropeptides, as well as a primat...
Source: Biochemical Pharmacology - December 20, 2020 Category: Drugs & Pharmacology Authors: Zeitzer JM Tags: Biochem Pharmacol Source Type: research

P2X7 receptor and the NLRP3 inflammasome: partners in crime.
e;n P Abstract Adenosine triphosphate (ATP) is a molecule that on one hand plays a central role in cellular energetics and which on the other is a ubiquitous signaling molecule when released into the extracellular media. Extracellular ATP accumulates in inflammatory environments where it acts as a damage-associated molecular pattern and activates the purinergic P2X receptor 7 (P2X7) in immune cells. P2X7 receptor activation induces the formation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3) inflammasome and the activation of the inflammatory caspase-1. Caspase-...
Source: Biochemical Pharmacology - December 20, 2020 Category: Drugs & Pharmacology Authors: Pelegrín P Tags: Biochem Pharmacol Source Type: research

Targeting Akt-associated microRNAs for cancer therapeutics.
Abstract The uncontrolled growth and spread of abnormal cells because of activating protooncogenes and/or inactivating tumor suppressor genes are the hallmarks of cancer. The PI3K/Akt signaling is one of the most frequently activated pathways in cancer cells responsible for the regulation of cell survival and proliferation in stress and hypoxic conditions during oncogenesis. Non-coding RNAs are a large family of RNAs that are not involved in protein-coding, and microRNAs (miRNAs) are a sub-set of non-coding RNAs with a single strand of 18-25 nucleotides. miRNAs are extensively involved in the post-transcriptional ...
Source: Biochemical Pharmacology - December 18, 2020 Category: Drugs & Pharmacology Authors: Adil MS, Khulood D, Somanath PR Tags: Biochem Pharmacol Source Type: research

Corrigendum to "CX-F9, a novel RSK2 inhibitor, suppresses cutaneous melanoma cells proliferation and metastasis through regulating autophagy" [Biochem. Pharmacol. 168 (2019), 14-25].
Corrigendum to "CX-F9, a novel RSK2 inhibitor, suppresses cutaneous melanoma cells proliferation and metastasis through regulating autophagy" [Biochem. Pharmacol. 168 (2019), 14-25]. Biochem Pharmacol. 2020 Dec 18;184:114372 Authors: Zhang X, Cai L, Zhao S, Long J, Li J, Wu L, Su J, Ling Zhang J, Tao J, Zhou J, Chen X, Peng C PMID: 33348166 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 18, 2020 Category: Drugs & Pharmacology Authors: Zhang X, Cai L, Zhao S, Long J, Li J, Wu L, Su J, Ling Zhang J, Tao J, Zhou J, Chen X, Peng C Tags: Biochem Pharmacol Source Type: research

Adenosine metabolism in the vascular system.
Abstract The concept of extracellular purinergic signaling was first proposed by Geoffrey Burnstock in the early 1970s. Since then, extracellular ATP and its metabolites ADP and adenosine have attracted an enormous amount of attention in terms of their involvement in a wide range of immunomodulatory, thromboregulatory, angiogenic, vasoactive and other pathophysiological activities in different organs and tissues, including the vascular system. In addition to significant progress in understanding the properties of nucleotide- and adenosine-selective receptors, recent studies have begun to uncover the complexity of ...
Source: Biochemical Pharmacology - December 16, 2020 Category: Drugs & Pharmacology Authors: Yegutkin GG Tags: Biochem Pharmacol Source Type: research

G protein-coupled receptors expressed and studied in yeast. The adenosine receptor as a prime example.
Abstract G protein-coupled receptors (GPCRs) are the largest class of membrane proteins with around 800 members in the human genome/proteome. Extracellular signals such as hormones and neurotransmitters regulate various biological processes via GPCRs, with GPCRs being the bodily target of 30-40% of current drugs on the market. Complete identification and understanding of GPCR functionality will provide opportunities for novel drug discovery. Yeast expresses three different endogenous GPCRs regulating pheromone and sugar sensing, with the pheromone pathway offering perspectives for the characterization of heterolog...
Source: Biochemical Pharmacology - December 15, 2020 Category: Drugs & Pharmacology Authors: Wang X, van Westen GJP, Heitman LH, IJzerman AP Tags: Biochem Pharmacol Source Type: research

Post-learning micro- and macro-structural neuroplasticity changes with time and sleep.
Abstract Neuroplasticity refers to the fact that our brain can partially modify both structure and function to adequately respond to novel environmental stimulations. Neuroplasticity mechanisms are not only operating during the acquisition of novel information (i.e., online) but also during the offline periods that take place after the end of the actual learning episode. Structural brain changes as a consequence of learning have been consistently demonstrated on the long term using non-invasive neuroimaging methods, but short-term changes remained more elusive. Fortunately, the swift development of advanced MR met...
Source: Biochemical Pharmacology - December 15, 2020 Category: Drugs & Pharmacology Authors: Whitney S, Philippe P Tags: Biochem Pharmacol Source Type: research

Nucleic Acids therapeutics using PolyPurine Reverse Hoogsteen hairpins.
, Ciudad CJ Abstract PolyPurine Reverse Hoogsteen hairpins (PPRHs) are DNA hairpins formed by intramolecular reverse Hoogsteen bonds which can bind to polypyrimidine stretches in dsDNA by Watson:Crick bonds, thus forming a triplex and displacing the fourth strand of the genomic DNA. PPRHs were first described as a gene silencing tool in vitro for DHFR, telomerase and survivin genes. Then, the effect of PPRHs directed against the survivin gene was also determined in vivo using a xenograft model of prostate cancer cells (PC3). Since then, the ability of PPRHs to inhibit gene expression has been explored in other gen...
Source: Biochemical Pharmacology - December 15, 2020 Category: Drugs & Pharmacology Authors: Noé V, Aubets E, Félix AJ, Ciudad CJ Tags: Biochem Pharmacol Source Type: research

Characterization of human pregnane X receptor activators identified from a screening of the Tox21 compound library.
In conclusion, the current study has identified 11 compounds as potentially novel or not well-characterized PXR activators. These compounds should further be studied for their potential effects on drug metabolism and drug-drug interactions due to the immense implications of being a PXR agonist. PMID: 33333074 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 14, 2020 Category: Drugs & Pharmacology Authors: Lynch C, Sakamuru S, Huang R, Niebler J, Ferguson SS, Xia M Tags: Biochem Pharmacol Source Type: research

Use of knockout mice to explore CNS effects of adenosine.
nha RA, Canas PM Abstract The initial exploration using pharmacological tools of the role of adenosine receptors in the brain, concluded that adenosine released as such acted on A1R to inhibit excitability and glutamate release from principal neurons throughout the brain and that adenosine A2A receptors (A2AR) were striatal-'specific' receptors controlling dopamine D2R. This indicted A1R as potential controllers of neurodegeneration and A2AR of psychiatric conditions. Global knockout of these two receptors questioned the key role of A1R and instead identified extra-striatal A2AR as robust controllers of neurodegen...
Source: Biochemical Pharmacology - December 14, 2020 Category: Drugs & Pharmacology Authors: Lopes CR, Lourenço VS, Tomé ÂR, Cunha RA, Canas PM Tags: Biochem Pharmacol Source Type: research

Akt and calcium-permeable AMPA receptor are involved in the effect of pinoresinol on amyloid β-induced synaptic plasticity and memory deficits.
Akt and calcium-permeable AMPA receptor are involved in the effect of pinoresinol on amyloid β-induced synaptic plasticity and memory deficits. Biochem Pharmacol. 2020 Dec 10;:114366 Authors: Yu J, Cho E, Kwon H, Jeon J, Seong Sin J, Kwon Park J, Kim JS, Woong Choi J, Jin Park S, Jun M, Choon Lee Y, Hoon Ryu J, Lee J, Moon M, Lee S, Hyun Cho J, Hyun Kim D Abstract Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by memory deficits. Although no drug has given promising results, synaptic dysfunction-modulating agents might be considered potential candi...
Source: Biochemical Pharmacology - December 10, 2020 Category: Drugs & Pharmacology Authors: Yu J, Cho E, Kwon H, Jeon J, Seong Sin J, Kwon Park J, Kim JS, Woong Choi J, Jin Park S, Jun M, Choon Lee Y, Hoon Ryu J, Lee J, Moon M, Lee S, Hyun Cho J, Hyun Kim D Tags: Biochem Pharmacol Source Type: research

Eg5 Targeting Agents : From new anti-mitotic based inhibitor discovery to cancer therapy and resistance.
Abstract Eg5, the product of Kif11 gene, also known as kinesin spindle protein, is a motor protein involved in the proper establishment of a bipolar mitotic spindle. Eg5 is one of the 45 different kinesins coded in the human genome of the kinesin motor protein superfamily. Over the last three decades Eg5 has attracted great interest as a promising new mitotic target. The identification of monastrol as specific inhibitor of the ATPase activity of the motor domain of Eg5 inhibiting the Eg5 microtubule motility in vitro and in cellulo sparked an intense interest in academia and industry to pursue the identification o...
Source: Biochemical Pharmacology - December 10, 2020 Category: Drugs & Pharmacology Authors: Garcia-Saez I, Skoufias DA Tags: Biochem Pharmacol Source Type: research

Insights into the role of GPX3, a highly efficient plasma antioxidant, in cancer.
Abstract Glutathione peroxidases are well known antioxidant enzymes. They catalyze the reduction of hydrogen peroxide or organic hydroperoxides using glutathione. Among the reported 8 GPxs, GPx3, a highly conserved protein and a major ROS scavenger in plasma, has been well studied and confirmed to play a vital role as a tumor suppressor in most cancers. Additionally, this gene is known to be epigenetically regulated. It is downregulated either by hypermethylation or genomic deletion. In this review, we summarized the role of GPX3 in various cancers, its use as a prognostic biomarker, and a potential target for cli...
Source: Biochemical Pharmacology - December 10, 2020 Category: Drugs & Pharmacology Authors: Nirgude S, Choudhary B Tags: Biochem Pharmacol Source Type: research

Phosphatase magnesium-dependent 1 δ (PPM1D), serine/threonine protein phosphatase and novel pharmacological target in cancer.
Phosphatase magnesium-dependent 1 δ (PPM1D), serine/threonine protein phosphatase and novel pharmacological target in cancer. Biochem Pharmacol. 2020 Dec 09;:114362 Authors: Nahta R, Castellino RC Abstract Aberrations in DNA damage response genes are recognized mediators of tumorigenesis and resistance to chemo- and radiotherapy. While protein phosphatase magnesium-dependent 1 δ (PPM1D), located on the long arm of chromosome 17 at 17q22-23, is a key regulator of cellular responses to DNA damage, amplification, overexpression, or mutation of this gene is important in a wide range of patholo...
Source: Biochemical Pharmacology - December 9, 2020 Category: Drugs & Pharmacology Authors: Nahta R, Castellino RC Tags: Biochem Pharmacol Source Type: research

Molecular Pharmacology of P2Y Receptor Subtypes.
n I Abstract Professor Geoffrey Burnstock proposed the concept of purinergic signaling via P1 and P2 receptors. P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular adenine and uracil nucleotides. Eight mammalian P2Y receptor subtypes have been identified. They are divided into two subgroups (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11) and (P2Y12, P2Y13, and P2Y14). P2Y receptors are found in almost all cells and mediate responses in physiology and pathophysiology including pain and inflammation. The antagonism of platelet P2Y12 receptors by cangrelor, ticagrelor or active metabolites of the thienopyridi...
Source: Biochemical Pharmacology - December 9, 2020 Category: Drugs & Pharmacology Authors: von Kügelgen I Tags: Biochem Pharmacol Source Type: research

PGE2 receptors in detrusor muscle: Drugging the undruggable for urgency.
Abstract Overactive bladder (OAB) syndrome is a prevalent condition of the lower urinary tract that causes symptoms, such as urinary frequency, urinary urgency, urge incontinence, and nocturia, and disproportionately affects women and the elderly. Current medications for OAB merely provide symptomatic relief with considerable limitations, as they are no more than moderately effective, not to mention that they may cause substantial adverse effects. Identifying novel molecular targets to facilitate the development of new medical therapies with higher efficacy and safety for OAB is in an urgent unmet need. Although t...
Source: Biochemical Pharmacology - December 9, 2020 Category: Drugs & Pharmacology Authors: Hou R, Yu Y, Jiang J Tags: Biochem Pharmacol Source Type: research

The prospects for targeting FcR as a novel therapeutic strategy in rheumatoid arthritis.
Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial membrane hyperplasia, infiltration of inflammatory cells and bone tissue destruction. Although there have been many measures taken for RA therapy in recent years, they are not sufficiently safe or effective. Thus, it is very important to develop new drugs and slow down damage to other healthy organs in the case of RA. Lately, immunoglobulin Fc receptors (FcRs), such as the IgG Fc receptor (FcγR), IgA Fc receptor (FcαR), and IgD Fc receptor (FcδR), have been found to be involved in inducing or sup...
Source: Biochemical Pharmacology - December 7, 2020 Category: Drugs & Pharmacology Authors: Yujing W, Wenwen P, Xiaoxi H, Aijun Z, Wei W Tags: Biochem Pharmacol Source Type: research

Overcoming interferon (IFN)- γ resistance ameliorates transforming growth factor (TGF)-β-mediated lung fibroblast-to-myofibroblast transition and bleomycin-induced pulmonary fibrosis.
Overcoming interferon (IFN)-γ resistance ameliorates transforming growth factor (TGF)-β-mediated lung fibroblast-to-myofibroblast transition and bleomycin-induced pulmonary fibrosis. Biochem Pharmacol. 2020 Dec 04;:114356 Authors: Chang CJ, Lin CF, Lee CH, Chuang HC, Shih FC, Wan SW, Tai C, Chen CL Abstract Abnormal activation of transforming growth factor (TGF)-β is a common cause of fibroblast activation and fibrosis. In bleomycin (BLM)-induced lung fibrosis, the marked expression of phospho-Src homology-2 domain-containing phosphatase (SHP) 2, phospho-signal transducer and activator...
Source: Biochemical Pharmacology - December 4, 2020 Category: Drugs & Pharmacology Authors: Chang CJ, Lin CF, Lee CH, Chuang HC, Shih FC, Wan SW, Tai C, Chen CL Tags: Biochem Pharmacol Source Type: research

Differential immunomodulatory Effect of PARP Inhibition in BRCA1 deficient and competent tumor cells.
In this study, we treat BRCA1 mutant cells derived from a patient with triple negative breast cancer and control cells for three weeks with veliparib, a PARPi, to determine if treatment with this drug induces increased levels of mutations and/or an inflammatory response. We show that long-term treatment with PARP inhibitor induces an inflammatory response in HCC1937 BRCA1 mutant cells. The levels of chromatin- bound PARP1 in the BRCA1 mutant cells correlate with significant upregulation of inflammatory genes and activation of the cyclic GMP-AMP synthase (cGAS)/ signaling effector stimulator of interferon genes (STING pathw...
Source: Biochemical Pharmacology - December 4, 2020 Category: Drugs & Pharmacology Authors: Alvarado-Cruz I, Mahmoud M, Khan M, Zhao S, Oeck S, Meas R, Clairmont K, Quintana V, Zhu Y, Porciuncula A, Wyatt H, Ma S, Shyr Y, Kong Y, LoRusso PM, Laverty D, Nagel ZD, Schalper KA, Krauthammer M, Sweasy JB Tags: Biochem Pharmacol Source Type: research

History of Geoff Burnstock's Research on P2 Receptors.
Abstract Geoffrey Burnstock is a purinergic signalling legend who's discoveries and conceptualisation created and shaped the field. His scientific achievements were extraordinary and sustained. They included his demonstration that ATP can act as a neurotransmitter and hence extracellular signalling molecule, which he championed despite considerable initial opposition to his proposal that ATP acts outside of its role as an energy source inside cells. He led on purine receptor classification: initially of the P1 and P2 receptor families, then the P2X and P2Y receptor families, and then subtypes of P2X and P2Y recept...
Source: Biochemical Pharmacology - December 3, 2020 Category: Drugs & Pharmacology Authors: Ralevic V Tags: Biochem Pharmacol Source Type: research

The methionine aminopeptidase 2 inhibitor, TNP-470, enhances the antidiabetic properties of sitagliptin in mice by upregulating xenin.
In conclusion, these data demonstrate that TNP-470 increases plasma and intestinal xenin levels, and augments the antidiabetic advantages of sitagliptin. PMID: 33279496 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 3, 2020 Category: Drugs & Pharmacology Authors: Craig SL, Gault VA, Flatt PR, Irwin N Tags: Biochem Pharmacol Source Type: research

MiRNAs directly targeting the key intermediates of biological pathways in pancreatic cancer.
Abstract Pancreatic Cancer (PC) is a severe form of malignancy all over the world. Delayed diagnosis and chemoresistance are the major factors contributing to its poor prognosis and high mortality rate. The genetic and epigenetic regulations of biological pathways further complicate the progression and chemotherapy response to this cancer. MicroRNAs (MiRNAs) involvement has been observed in all types of cancers including PC. The understanding and categorization of miRNAs according to their specific targets are very important to develop early diagnostic and therapeutic interventions. The current review, emphasizing...
Source: Biochemical Pharmacology - December 3, 2020 Category: Drugs & Pharmacology Authors: Sarwar A, Wang B, Su Q, Zhang Y Tags: Biochem Pharmacol Source Type: research

Targeting tumor-associated macrophages as an antitumor strategy.
Abstract Tumor-associated macrophages (TAMs) are the most widely infiltrating immune cells in the tumor microenvironment (TME). Clinically, the number of TAMs is closely correlated with poor outcomes in multiple cancers. The biological actions of TAMs are complex and diverse, including mediating angiogenesis, promoting tumor invasion and metastasis, and building an immunosuppressive microenvironment. Given these pivotal roles of TAMs in tumor development, TAM-based strategies are attractive and used in certain tumor therapies, including inhibition of angiogenic signalling, blockade of the immune checkpoint, and ma...
Source: Biochemical Pharmacology - December 3, 2020 Category: Drugs & Pharmacology Authors: Cheng N, Bai X, Shu Y, Ahmad O, Shen P Tags: Biochem Pharmacol Source Type: research

Targeting ROCK1/2 blocks cell division and induces mitotic catastrophe in hepatocellular carcinoma.
CONCLUSIONS: Both ROCK1 and ROCK2 are required for HCC cell division and growth. Targeting ROCK1 or ROCK2 rather than both can serve as a potential approach for HCC treatment and may reduce the side effects. PMID: 33278350 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 2, 2020 Category: Drugs & Pharmacology Authors: Wu H, Chen Y, Li B, Li C, Guo J, You J, Hu X, Kuang D, Qi S, Liu P, Li L, Xu C Tags: Biochem Pharmacol Source Type: research

EP4 receptor agonist L-902688 augments cytotoxic activities of ibrutinib, idelalisib, and venetoclax against chronic lymphocytic leukemia cells.
an I Abstract Treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) has significantly improved more recently with the approval of several new agents, including ibrutinib, idelalisib, and venetoclax. Despite the outstanding efficacies observed with these agents, these treatments are sometimes discontinued due to toxicity, unresponsiveness, transformation of the disease and/or resistance. Constitutive NF-κB activation that protects CLL cells from apoptotic stimuli represents one of molecular mechanisms that underlie the emergence of drug resistance. As prostaglandin E (EP)4 rece...
Source: Biochemical Pharmacology - December 2, 2020 Category: Drugs & Pharmacology Authors: Nabergoj S, Markovič T, Avsec D, Gobec M, Podgornik H, Jakopin Ž, Mlinarič-Raščan I Tags: Biochem Pharmacol Source Type: research

P2X receptors in cancer growth and progression.
Abstract It is increasingly appreciated that ion channels have a crucial role in tumors, either as promoters of cancer cell growth, or modulators of immune cell functions, or both. Among ion channels, P2X receptors have a special status because they are gated by ATP, a common and abundant component of the tumor microenvironment. Furthermore, one P2X receptor, i.e. P2X7, may also function as a conduit for ATP release, thus fuelling the increased extracellular ATP level in the tumor interstitium. These findings show that P2X receptors and extracellular ATP are indissoluble partners and key regulators of tumor growth...
Source: Biochemical Pharmacology - November 27, 2020 Category: Drugs & Pharmacology Authors: Di Virgilio F, Vultaggio-Poma V, Sarti AC Tags: Biochem Pharmacol Source Type: research