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  • ||||||||||  Journal:  Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells. (Pubmed Central) -  Feb 20, 2021   
    Our data show that the COX inhibitors Sulindac and Diclofenac in combination with CHIR99021 (GSK-3 inhibitor) efficiently induce cardiac differentiation of hPSCs...In conclusion, this study demonstrates that COX inhibition efficiently induced cardiogenesis via modulation of COX and Wnt pathway and the generated cardiomyocytes express cardiac-specific structural markers as well as exhibit typical calcium transients and action potentials. These cardiomyocytes also responded to cardiotoxicants and can be relevant as an in vitro cardiotoxicity screening model.
  • ||||||||||  indomethacin / Generic mfg.
    Review, Journal:  Indomethacin for symptomatic patent ductus arteriosus in preterm infants. (Pubmed Central) -  Feb 20, 2021   
    High-certainty evidence shows that indomethacin is effective in closing a symptomatic PDA compared to placebo or no treatment in preterm infants. Evidence is insufficient regarding effects of indomethacin on other clinically relevant outcomes and medication-related adverse effects.
  • ||||||||||  Journal, PARP Biomarker:  Selective deficiency in endothelial PTP1B protects from diabetes and endoplasmic reticulum stress-associated endothelial dysfunction via preventing endothelial cell apoptosis. (Pubmed Central) -  Feb 12, 2021   
    Nitric oxide synthase inhibition with l-NAME abolished relaxation in the presence and absence of ERS, but neither reactive oxygen species scavenging with tempol or peg-catalase, nor cyclooxygenase inhibition with indomethacin prevented ERS-mediated endothelial dysfunction...Lastly, acute ERS inhibition in aortic rings and selective deficiency of endothelial PTP1B in mice protected mice from diabetes-induced endothelial dysfunction. Altogether, these data support the contribution of the p38/JNK-apoptosis pathway in ERS-mediated endothelial dysfunction and present endothelial PTP1B as a major regulator of endothelial cell viability in conduit vessels and a potential target for the management of macrovascular diseases in diabetes.
  • ||||||||||  Review, Journal:  Overview on the Discovery and Development of Anti-Inflammatory Drugs: Should the Focus Be on Synthesis or Degradation of PGE? (Pubmed Central) -  Feb 12, 2021   
    As leukotrienes formed via the 5-lipoxygenase (5-LOX) pathway also play an important role in the mediation of inflammation, efforts are also being made to target both COX and LOX pathways. This review focuses on addressing the following three points: 1) How NSAIDs and COXIBs are associated with gastric, renal and cardiac side-effects; 2) Should the focus be on the targets upstream or downstream of PGE; and 3) the status of alternative targets being explored for the discovery and development of anti-inflammatory drugs without side-effects.
  • ||||||||||  Journal:  BCL‑3 promotes cyclooxygenase‑2/prostaglandin E2 signalling in colorectal cancer. (Pubmed Central) -  Feb 9, 2021   
    Taken together, the results of the present study identified a novel role for BCL‑3 in colorectal cancer and suggested that expression of BCL‑3 may be a key determinant in the COX‑2‑meditated response to inflammatory cytokines in colorectal tumour cells. These results suggest that targeting BCL‑3 to suppress PGE2 synthesis may represent an alternative or complementary approach to using non‑steroidal anti‑inflammatory drugs [(NSAIDs), which inhibit cyclooxygenase activity and suppress the conversion of arachidonic acid to prostaglandin], for prevention and/or recurrence in PGE2‑driven tumorigenesis.
  • ||||||||||  ibuprofen / Generic mfg.
    Review, Journal:  Non-steroidal anti-inflammatory drugs on core body temperature during exercise: A systematic review. (Pubmed Central) -  Feb 9, 2021   
    The majority suggest taking non-selective NSAIDs (e.g., aspirin) 1-14 days before exercise does not significantly affect Tc during exercise. However, it remains unclear whether Tc increases, decreases, or does not change during exercise with other NSAID drug types (e.g., naproxen), higher dosages, chronic use, greater exercise intensity, and/or greater environmental temperatures.
  • ||||||||||  Journal:  Pharmacological appraisal of ligustrazine based cyclohexanone analogs as inhibitors of inflammatory markers. (Pubmed Central) -  Feb 7, 2021   
    Additionally, the compounds 1b, 1d, 1e, 2n, and 2o were shown to be significant inhibitors of COX-1 activity with IC values 0.09 to 0.7 μM. The outcomes of assays for COX inhibition demonstrated that the same compounds had a further strong inhibitive influence on the COX-2 enzyme, and certain compounds such as 1d, 1e, and 2n demonstrated enhanced potency compared with positive controls.
  • ||||||||||  Journal:  Periplanetols A-F, phenolic compounds from Periplaneta americana with potent COX-2 inhibitory activity. (Pubmed Central) -  Feb 4, 2021   
    Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. Biological evaluation toward COX-2 inhibition revealed that compounds 1, 2, and 10 could inhibit COX-2 activity with the IC values of 768.0 nM, 617.7 nM, and 599.5 nM respectively, indicating their potential in developping novel agents against inflammation related disorders.
  • ||||||||||  [VIRTUAL] Endometriosis, Genetics, and Epigenetics (On-Demand) -  Feb 2, 2021 - Abstract #ENDO2021ENDO_2414;    
    Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
  • ||||||||||  Journal:  Cyclooxygenase inhibition prior to ventricular fibrillation induced ischemia reperfusion injury impairs survival and outcomes. (Pubmed Central) -  Jan 26, 2021   
    These results along with literature review of focal I/R in animal models with COX-2 overexpression, human studies of CA, and post myocardial infarction treatment with NSAIDs, support the hypothesis that NSAIDs prior to an I/R event impairs survival and outcomes. Specifically, predominantly COX-1 inhibition impairs survival, and COX-2 inhibition induces myocardial damage, autonomic nervous system dysfunction, and increases the risk for all-cause mortality and morbidity in humans post-MI which has significant implications for the nearly 10% of the population who are taking NSAIDs.
  • ||||||||||  ibuprofen / Generic mfg.
    Journal:  First report of substituted 2H-pyranoids from brown seaweed Turbinaria conoides with antioxidant and anti-inflammatory activities. (Pubmed Central) -  Jan 15, 2021   
    Likewise, potential bioactivity of the 2H-pyran derivative, 1 against 5-lipoxygenase (IC ∼ 1 mg mL) along with higher index of selectivity (COX-1 inhibitory/COX-2 inhibitory 1.88) indicated their selective anti-inflammatory properties against inducible inflammatory mediators than that displayed by commercially available non-steroidal anti-inflammatory drug (ibuprofen, 0.44)...Structure activity relationship analysis of the studied compounds showed that the antioxidative and anti-inflammatory properties were directly proportional to their electronic properties. The previously undescribed 2H-pyranoids might constitute as potential antioxidative and anti-inflammatory pharmacophores for medicinal applications.
  • ||||||||||  Review, Journal:  Identification of Active Compounds From Yi Nationality Herbal Formula Wosi Influencing COX-2 and VCAM-1 Signaling. (Pubmed Central) -  Jan 15, 2021   
    Meanwhile, the down-regulated protein expression of COX-2 and VCAM-1 in synovial tissue sections from ankle joints of experiments rats were confirmed by immunohistochemistry analysis after the Wosi treatment. In conclusion, three oleanolic acid glycosides were implied as mainly efficient compounds in Yi nationality herbal formula Wosi for arthritis therapy via selectively influencing COX-2 and VCAM-1 signaling.
  • ||||||||||  indomethacin / PLx Pharma Inc, Generic mfg., propranolol / Generic mfg.
    Journal:  Thromboxane A in the paraventricular hypothalamic nucleus mediates glucoprivation-induced adrenomedullary outflow. (Pubmed Central) -  Jan 8, 2021   
    Furthermore, 2-DG administration elevated the thromboxane B level, a metabolite of thromboxane A in PVN microdialysates. Our results suggest that glucoprivation-induced activation of α- and β-adrenergic receptor in the brain including the PVN and then thromboxane A production in the PVN, which are essential for the 2-DG-induced elevations of both plasma adrenaline and noradrenaline levels.
  • ||||||||||  Review, Journal:  Anti-Inflammatory Drugs as Anticancer Agents. (Pubmed Central) -  Jan 8, 2021   
    In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.
  • ||||||||||  Journal:  Known compounds and new lessons: structural and electronic basis of flavonoid based bioactivities. (Pubmed Central) -  Jan 2, 2021   
    Here we report molecular dynamics data from 16 Flavonoid-COX-2 complexes performed for 50 nano-seconds each that demonstrates key structural and dynamic aspects of flavonoid based COX inhibition in light of observed experimental facts. Interaction analysis and evaluation of side chain dynamics presented in current study are in well agreement with the empirical study and is hoped to pave new avenues towards design and development of COX-2 selective chemical agents.
  • ||||||||||  Preclinical, Journal:  Roles of Dkk2 in the Linkage from Muscle to Bone during Mechanical Unloading in Mice. (Pubmed Central) -  Dec 30, 2020   
    In conclusion, we showed that muscle and serum Dkk2 levels are positively and negatively regulated during mechanical unloading and hypergravity in mice, respectively. An increase in Dkk2 expression in the skeletal muscle might contribute to disuse- and microgravity-induced bone and muscle loss.
  • ||||||||||  aspirin / Generic mfg.
    [VIRTUAL] Mechanistic Review of Niacin – Induced Flushing and Mitigation () -  Dec 26, 2020 - Abstract #ASHP2020ASHP_2835;    
    Cox inhibitors are concurrently used to reduce the flushing effects of niacin by limiting the vasodilatory effect. Understanding the mechanism mediated by the GPR109A receptor serves as a potential target for future pharmacotherapy agents to mitigate the flushing reaction.
  • ||||||||||  Journal:  A Second Generation Prostanoid Receptor Antagonist Acting at Multiple Receptor Subtypes. (Pubmed Central) -  Dec 22, 2020   
    These findings suggest important effects on T cell skewing and disease modification by this class of therapeutic agents. AGN 225660 exhibited good ocular bioavailability and was active in reducing ocular inflammation associated with phacoemulsification surgery, LPS, and arachidonic acid induced uveitis.
  • ||||||||||  acetazolamide / Generic mfg.
    Journal:  Adjunctive acetazolamide therapy for the treatment of Bartter syndrome. (Pubmed Central) -  Dec 18, 2020   
    Our data suggest that mitochondrial modulation with NIR attenuates ischemia-reperfusion injury and evokes a sustained reduction in infarct volume following ischemic stroke. Our data define a new physiologic and therapeutic role of acetazolamide for the management of children with Bartter syndrome.
  • ||||||||||  Desferal (deferoxamine) / Kermanshah University of Medical Sciences, Novartis, U0126 / Promega, SP600125 / BMS
    Preclinical, Journal:  Tert-Butyl Hydroperoxide Stimulated Apoptosis Independent of Prostaglandin E and IL-6 in the HTR-8/SVneo Human Placental Cell Line. (Pubmed Central) -  Dec 18, 2020   
    TBHP-stimulated IL-6 release was blocked by PD169316 but unaltered by indomethacin. These data suggest that TBHP-stimulated IL-6 release and caspase 3/7 activation were independent of PGE yet were interrupted by treatments with known antioxidant properties, providing new insight into relationships between PGE, IL-6, and apoptosis under conditions of chemically induced cellular oxidation.
  • ||||||||||  Preclinical, Journal:  The neuropathic phenotype of the K/BxN transgenic mouse with spontaneous arthritis: pain, nerve sprouting and joint remodeling. (Pubmed Central) -  Dec 16, 2020   
    We report that both males and females display a severe sustained tactile allodynia which is reduced by gabapentin but not the potent cyclooxygenase inhibitor ketorolac...Thus, based on the changes in dorsal horn, DRG and peripheral innervation, we suggest that the adult K/BxN transgenic arthritic mice display a neuropathic phenotype, an assertion consistent with the analgesic pharmacology seen in this animal. These results indicate the relevance of this model to our understanding of the nociceptive processing which underlies the chronic pain state that evolves secondary to persistent joint inflammation.