Day: November 30, 2022

Han, Jung Woo published the artcileIsoproterenol-induced hypertrophy of neonatal cardiac myocytes and H9c2 cell is dependent on TRPC3-regulated CaV1.2 expression, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is TRPC3 calcium channel signaling cardiac myocyte hypertrophy; Ca(2+) influx; Ca(V)1.2; L-type Ca(2+) channel; NFAT3; Neonatal cardiac hypertrophy; Transient receptor potential canonical channel 3.

CaV1.2 and transient receptor potential canonical channel 3 (TRPC3) are two proteins known to have important roles in pathol. cardiac hypertrophy; however, such roles still remain unclear. A better understanding of these roles is important for furthering the clin. understanding of heart failure. We previously reported that Trpc3-knockout (KO) mice are resistant to pathol. hypertrophy and that their CaV1.2 protein expression is reduced. In this study, we aimed to examine the relationship between these two proteins and characterize their role in neonatal cardiomyocytes. We measured CaV1.2 expression in the hearts of wild-type (WT) and Trpc3-/- mice, and examined the effects of Trpc3 knockdown and overexpression in the rat cell line H9c2. We also compared the hypertrophic responses of neonatal cardiomyocytes cultured from Trpc3-/- mice to a representative hypertrophy-causing drug, isoproterenol (ISO), and measured the activity of nuclear factor of activated T cells 3 (NFAT3) in neonatal cardiomyocytes (NCMCs). We inhibited the L-type current with nifedipine, and measured the intracellular calcium concentration using Fura-2 with 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced Ba2+ influx. When using the Trpc3-mediated Ca2+ influx, both intracellular calcium concentration and calcium influx were reduced in Trpc3-KO myocytes. Not only was the expression of CaV1.2 greatly reduced in Trpc3-KO cardiac lysate, but the size of the CaV1.2 currents in NCMCs was also greatly reduced. When NCMCs were treated with Trpc3 siRNA, it was confirmed that the expression of CaV1.2 and the intracellular nuclear transfer activity of NFAT decreased. In H9c2 cells, the ISO activated- and verapamil inhibited- Ca2+ influxes were dramatically attenuated by Trpc3 siRNA treatment. In addition, it was confirmed that both the expression of CaV1.2 and the size of H9c2 cells were regulated according to the expression and activation level of TRPC3. We found that after stimulation with ISO, cell hypertrophy occurred in WT myocytes, while the increase in size of Trpc3-KO myocytes was greatly reduced. These results suggest that not only the cell hypertrophy process in neonatal cardiac myocytes and H9c2 cells were regulated according to the expression level of CaV1.2, but also that the expression level of CaV1.2 was regulated by TRPC3 through the activation of NFAT.

Cell Calcium published new progress about Cardiac hypertrophy. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Feric, Nicole T. published the artcileEngineered cardiac tissues generated in the biowire II: a platform for human-based drug discovery, Formula: C17H18N2O6, the main research area is heart tissue cardiomyocyte drug discovery; Cardiomyocytes; contractility; drug discovery; drug safety; engineered cardiac tissue; in vitro models.

Recent advances in techniques to differentiate human induced pluripotent stem cells (hiPSCs) hold the promise of an unlimited supply of human derived cardiac cells from both healthy and disease populations. That promise has been tempered by the observation that hiPSC-derived cardiomyocytes (hiPSC-CMs) typically retain a fetal-like phenotype, raising concern about the translatability of the in vitro data obtained to drug safety, discovery, and development studies. The Biowire II platform was used to generate 3D engineered cardiac tissues (ECTs) from hiPSC-CMs and cardiac fibroblasts. Long term elec. stimulation was employed to obtain ECTs that possess a phenotype like that of adult human myocardium including a lack of spontaneous beating, the presence of a pos. force-frequency response from 1 to 4 Hz and prominent postrest potentiation. Pharmacol. studies were performed in the ECTs to confirm the presence and functionality of pathways that modulate cardiac contractility in humans. Canonical responses were observed for compounds that act via the β-adrenergic/cAMP-mediated pathway, eg, isoproterenol and milrinone; the L-type calcium channel, eg, FPL64176 and nifedipine; and indirectly effect intracellular Ca2+ concentrations, eg, digoxin. Expected pos. inotropic responses were observed for compounds that modulate proteins of the cardiac sarcomere, eg, omecamtiv mecarbil and levosimendan. ECTs generated in the Biowire II platform display adult-like properties and have canonical responses to cardiotherapeutic and cardiotoxic agents that affect contractility in humans via a variety of mechanisms. These data demonstrate that this human-based model can be used to assess the effects of novel compounds on contractility early in the drug discovery and development process.

Toxicological Sciences published new progress about Cardiac contraction. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Liu, Gang published the artcileExperimental Study on Seawater Applications in Organic Reactions, Recommanded Product: 2-Chloro-4-methylpyridin-3-amine, the main research area is organic reaction seawater application industrial production.

Background: Total water resources account for only 2.5% of freshwater on earth, and only 1% of total water resources can be exploited by humans. The development of practical methods of seawater desalination and comprehensive utilization technol. can help address the shortage of freshwater resources in the world, and achieve sustainable use of water resources to ensure sustainable development in a society. Direct seawater utilization currently involves industrial cooling water, water for agricultural irrigation, and flushing water. Applications in aqueous phase organic reactions, particularly the direct use of seawater in industrial organic synthesis reactions, are seldom reported. Methods: we used seawater instead of freshwater in selected basic organic chem. reactions. The application of seawater in aqueous phase organic reactions was systematically investigated. Six types of reactions were studied using freshwater and seawater, namely, preparation of acetanilide, synthesis of mandelic acid, Cannizzaro reaction, Hofmann degradation reaction, preparation of quinazolin-4-one, and preparation of adipic acid. Results: Seven organic compounds were produced. Results show that some organic reactions could directly use seawater or treated seawater as an alternative to freshwater. The yields of the reactions using seawater could be compared with literature values, or were even better than literature values. Conclusion: This research provides new opportunities for the comprehensive utilization of seawater. Some organic reactions could directly use seawater or treated seawater instead of freshwater. The use of seawater instead of freshwater for organic reactions in industrial production may greatly conserve freshwater resources and protect the environment.

Letters in Organic Chemistry published new progress about Cannizzaro reaction. 133627-45-9 belongs to class pyridine-derivatives, name is 2-Chloro-4-methylpyridin-3-amine, and the molecular formula is C6H7ClN2, Recommanded Product: 2-Chloro-4-methylpyridin-3-amine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Joyce, Paul published the artcileTIRF Microscopy-Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica, SDS of cas: 72509-76-3, the main research area is felodipine drug permeation lipid membrane mesoporous silica; drug delivery; membrane permeation; mesoporous silica; supported lipid bilayer; total internal reflection fluorescence.

There is an urgent demand for analytic approaches that enable precise and representative quantification of the transport of biol. active compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence microscopy confined to a �00 nm thick mesoporous silica substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally resolved membrane permeation kinetics of a small-mol. model drug, felodipine, while simultaneously controlling the integrity of, and monitoring the drug binding to, the cell membrane mimic. By contrasting the permeation behavior of pure felodipine with felodipine coupled to the permeability enhancer caprylate (C8), we provide evidence for C8-facilitated transport across lipid membranes, thus validating the potential for this approach to successfully quantify carrier system-induced changes to cellular membrane permeation.

Angewandte Chemie, International Edition published new progress about Blood-brain barrier. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, SDS of cas: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Peng, De-wei published the artcileConnexin 43 participates in atrial electrical remodelling through colocalization with calcium channels in atrial myocytes, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is connexin 43 calcium channel atrial elec remodelling fibrillation myocyte; HL-1 cells; L type calcium channel current; T type calcium channel current; atrial fibrillation; connexin 43.

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by elec. and/or structural remodelling. In the present study, author hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.2 and connexin 43 (Cx43) and basal ICa,L were decreased in AF subjects compared to sinus rhythm (SR) controls. In cultured atrium-derived myocytes (HL-1 cells), knocking-down of Cx43 or incubation with 30 mmol/L glycyrrhetinic acid significantly inhibited protein levels of Cav1.2 and Cav3.1 and the c.d. of ICa,L and ICa,T. Incubation with nifedipine or mibefradil decreased the protein level of Cx43 in HL-1 cells. Moreover, Cx43 was colocalized with Cav1.2 and Cav3.1 in atrial myocytes. Therefore, Cx43 might regulate the ICa,L and ICa,T through colocalization with calcium channel subunits in atrial myocytes, representing a potential pathogenic mechanism in AF.

Clinical and Experimental Pharmacology and Physiology published new progress about Atrial fibrillation. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Jian-Qi published the artcileEffects of allisartan isoproxil on blood pressure and target organ injury in patients with mild to moderate essential hypertension, COA of Formula: C17H18N2O6, the main research area is essential hypertension organ injury blood pressure allisartan isoproxil.

Evidence has shown that angiotensin II type 1 receptor antagonists have lower blood pressure and have target organ protective effects, but this is not the case for the drug allisartan isoproxil. The aim of this study was to evaluate the effects of allisartan isoproxil on blood pressure and target organ injury in patients with mild to moderate essential hypertension.In total, 80 essential hypertensive participants were randomly divided into an allisartan group and a nifedipine group (n=40 per group), and their blood pressure was measured once per mo for 6 mo. A 2-dimensional echocardiogram was performed at baseline and at the end of the study. The serum levels of renal injury indexes, endothelial function markers, inflammatory factors, blood biochem. assays and urinary measurements were determined at baseline and at 6 mo.At the end of the study, both systolic and diastolic blood pressure were significantly decreased in the allisartan group compared with baseline and showed the same antihypertensive effect as the nifedipine group. Meanwhile, the left ventricular remodeling, 24-h levels of urinary microalbumin, endothelial dysfunction, and arterial stiffness were all significantly improved compared with that of the baseline and the nifedipine group (all P<.05).The present study showed that allisartan isoproxil had favorable blood pressure lowering and heart, renal, and endothelial protective effects in patients with mild to moderate essential hypertension. Medicine (Philadelphia, PA, United States) published new progress about Antiglaucoma agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, COA of Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yamazaki, Kei published the artcileHepatocyte growth factor exhibits anti-fibrotic effects in an in vitro model of nifedipineinduced gingival overgrowth, Related Products of pyridine-derivatives, the main research area is gingiva nifedipine hepatocyte growth factor antifibrotic; drug-induced gingival overgrowth; hepatocyte growth factor; nifedipine.

Purpose: The aim of this study was to establish an in vitro model of nifedipine-induced gingival overgrowth and characterize the anti-fibrotic effect of hepatocyte growth factor (HGF) using this model. Methods: Human gingival fibroblasts were cultured-treated with 0.1, 1, or 10μg/mL nifedipine or 10 ng/mL IL-1β + 0.1, 1, or 10μg/mL nifedipine (0.1N, 1N, 10N, IL + 0.1N, IL + 1N, IL + 10N). Cell proliferation and levels of type I collagen, TGF-β1, CCN2/CTGF, and α-SMA were measured 48 h after the simultaneous addition of 10 and 50 ng/mL HGF (10 and 50HGF) along with IL-1β and nifedipine. Type I collagen was measured after administration of anti-HGF neutralizing antibody. Results: Significant increases in type I collagen, TGF-β1, and CCN2/ CTGF were observed after treatment in the 1N and IL + 0.1N groups. Levels of type I collagen and CCN2/CTGF differed significantly between the IL + 0.1N group and the IL + 0.1N + 50HGF group. Production of type I collagen increased significantly following addition of anti-HGF antibody. Conclusion: This study demonstrated the establishment of an in vitro model of nifedipine-induced gingival overgrowth by showing increased collagen levels. Experiments using this model suggested that HGF exerts anti-fibrotic effects.

Journal of Oral Science published new progress about Antifibrotic agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Seo, Mi Seon published the artcileEmpagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K+ channels, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is empagliflozin antidiabetic agent vasodilatory; Aorta; Empagliflozin; Protein kinase G; Voltage-dependent K(+) (Kv) channel.

We investigated the vasodilatory effects of empagliflozin (a sodium-glucose co-transporter 2 inhibitor) and the underlying mechanisms using rabbit aorta. Empagliflozin induced vasodilation in a concentration-dependent manner independently of the endothelium. Likewise, pretreatment with the nitric oxide synthase inhibitor L-NAME or the SKca inhibitor apamin together with the IKca inhibitor TRAM-34 did not impact the vasodilatory effects of empagliflozin. Pretreatment with the adenylyl cyclase inhibitor SQ22536 or a guanylyl cyclase inhibitor ODQ or a protein kinase A (PKA) inhibitor KT5720 also did not alter the vasodilatory response of empagliflozin. However, the vasodilatory effects of empagliflozin were significantly reduced by pretreatment with the protein kinase G (PKG) inhibitor KT5823. Although application of the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide, large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline, or inwardly rectifying K+ (Kir) channel inhibitor Ba2+ did not impact the vasodilatory effects of empagliflozin, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of empagliflozin. Pretreatment with DPO-1 (Kv1.5 channel inhibitor), guangxitoxin (Kv2.1 channel inhibitor), or linopirdine (Kv7 channel inhibitor) had little effect on empagliflozin-induced vasodilation. Application of nifedipine (L-type Ca2+ channel inhibitor) or thapsigargin (sarco-endoplasmic reticulum Ca2+-ATPase pump inhibitor) did not impact empagliflozin-induced vasodilation. Therefore, empagliflozin induces vasodilation by activating PKG and Kv channels.

Toxicology and Applied Pharmacology published new progress about Antidiabetic agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Turkes, Cuneyt published the artcileAnti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity, Application In Synthesis of 21829-25-4, the main research area is cinnarizine calcium channel blocker antidiabetic agent aldose reductase; Aldose reductase; Calcium channel blockers; Inhibition; Purification.

Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some calcium channel blockers and the enzyme. It was found that calcium channel blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87-8.77μM and Ki constants in the range of 2.07 ± 0.72-5.62 ± 1.53μM. The calcium channel blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (Ki: 2.07 ± 0.72μM). They may be useful in the treatment and/or prevention of diabetic complications.

Applied Biochemistry and Biotechnology published new progress about Antidiabetic agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Suriyapakorn, Bovornpat published the artcileComparison of potential drug-drug interactions with metabolic syndrome medications detected by two databases, Category: pyridine-derivatives, the main research area is atenolol bisoprolol enalapril imidapril antiplatelet antilipemic antihypertensive metabolic syndrome.

Drug-drug interactions (DDIs) are one of the most common drug-related problems. Recently, electronic databases have drug interaction tools to search for potential DDIs, for example, Micromedex and Drugs.com. However, Micromedex and Drugs.com have different abilities in detecting potential DDIs, and this might cause misinformation to occur between patients and health care providers. The aim of this study was to compare the ability of Micromedex and Drugs.com to detect potential DDIs with metabolic syndrome medications using the drug list from the U-central database, King Chulalongkorn Memorial Hospital in Apr. 2019. There were 90 available drugs for the treatment of the metabolic syndrome and its associated complications, but six were not found in the Micromedex and Drugs.com databases; therefore, only 84 items were used in the present study. There were 1,285 potential DDI pairs found by the two databases. Micromedex reported DDIs of 724 pairs, while, Drugs.com reported 1,122 pairs. For the severity of the potential DDI reports, the same severity occurred between the two databases of 481 pairs (37.43%) and a different severity for 804 pairs (62.57%). Drugs.com had a higher sensitivity to detect potential DDIs by approx. 1.5-fold, but Micromedex supplied more informative documentation for the severity classification. Therefore, pharmacists should use at least two databases to evaluate potential DDIs and determine the appropriate drug regimens for physician communications and patient consultations.

PLoS One published new progress about Antidiabetic agents. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem