Tag: M.W=200-350

Kim, Seul Gi published the artcileNifedipine-induced AMPK activation alleviates senescence by increasing autophagy and suppressing of Ca2+ levels in vascular smooth muscle cells, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is vascular smooth muscle cell senescence autophagy calcium AMPK nifedipine; AMPK; Autophagy; Ca(2+); Nifedipine; Senescence; Vascular smooth muscle cell.

Calcium (Ca2+) homeostasis is disrupted during aging in several cell types and this disruption leads to autophagy impairment. The mechanisms regarding Ca2+, senescence, and autophagy need to be elucidated. Therefore, we hypothesized that cellular senescence can be improved by regulating Ca2+ level and autophagy activity. We identified that hydrogen peroxide (H2O2)-induced senescence was accompanied by Ca2+ elevation, impairment of autophagic flux and increase of mammalian target of rapamycin (mTOR) phosphorylation in VSMCs. The treatment of nifedipine dose-dependently suppressed H2O2-induced senescence by reducing Ca2+ entry, autophagy impairment and mTOR signaling, and this suppression was found to be related to senescence-associated β-galactosidase (SA-β-gal) activity and the expressions of senescence marker protein 30 (SMP30), p53, and p21. Furthermore, H2O2-induced autophagy impairment also accelerated senescence and accumulations of ubiquitinated proteins. AMPK inhibition or transfection with AMPK siRNA showed that the anti-senescence effect of nifedipine involved AMPK activation. These results suggest nifedipine-inducted AMPK activation suppresses VSMC senescence by regulating autophagic flux and Ca2+ levels.

Mechanisms of Ageing and Development published new progress about Autophagy. 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

Hu, H. published the artcileEngineering of a spider peptide via conserved structure-function traits optimizes sodium channel inhibition in vitro and anti-nociception in vivo, SDS of cas: 21829-25-4, the main research area is spider peptide conserved structure function sodium channel inhibition antinociception; chronic pain; neurological diseases; optimization; peptide engineering; rational design; sodium channel; spider peptide; therapy.

Venom peptides are potent and selective modulators of voltage-gated ion channels that regulate neuronal function both in health and in disease. We previously identified the spider venom peptide Tap1a from the Venezuelan tarantula Theraphosa apophysis that targeted multiple voltage-gated sodium and calcium channels in visceral pain pathways and inhibited visceral mechano-sensing neurons contributing to irritable bowel syndrome. In this work, alanine scanning and domain activity anal. revealed Tap1a inhibited sodium channels by binding with nanomolar affinity to the voltage-sensor domain II utilizing conserved structure-function features characteristic of spider peptides belonging to family NaSpTx1. In order to speed up the development of optimized NaV-targeting peptides with greater inhibitory potency and enhanced in vivo activity, we tested the hypothesis that incorporating residues identified from other optimized NaSpTx1 peptides into Tap1a could also optimize its potency for NaVs. Applying this approach, we designed the peptides Tap1a-OPT1 and Tap1a-OPT2 exhibiting significant increased potency for NaV1.1, NaV1.2, NaV1.3, NaV1.6 and NaV1.7 involved in several neurol. disorders including acute and chronic pain, motor neuron disease and epilepsy. Tap1a-OPT1 showed increased potency for the off-target NaV1.4, while this off-target activity was absent in Tap1a-OPT2. This enhanced potency arose through a slowed off-rate mechanism. Optimized inhibition of NaV channels observed in vitro translated in vivo, with reversal of nocifensive behaviors in a murine model of NaV-mediated pain also enhanced by Tap1a-OPT. Mol. docking studies suggested that improved interactions within loops 3 and 4, and C-terminal of Tap1a-OPT and the NaV channel voltage-sensor domain II were the main drivers of potency optimization. Overall, the rationally designed peptide Tap1a-OPT displayed new and refined structure-function features which are likely the major contributors to its enhanced bioactive properties observed in vivo. This work contributes to the rapid engineering and optimization of potent spider peptides multi-targeting NaV channels, and the research into novel drugs to treat neurol. diseases.

Frontiers in Molecular Biosciences published new progress about Acute pain. 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, SDS of cas: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Palmquist, Karl H. published the artcileReciprocal cell-ECM dynamics generate supracellular fluidity underlying spontaneous follicle patterning, Quality Control of 21829-25-4, the main research area is supracellular fluidity extracellular matrix follicle cell; active soft matter; biophysics; contractility; emergence; extracellular matrix; mechanics; mechanosensation; morphogenesis; multicellular; organogenesis; periodic patterning; self-organization; skin.

During vertebrate embryogenesis, cell collectives engage in coordinated behavior to form tissue structures of increasing complexity. In the avian skin, assembly into follicles depends on intrinsic mech. forces of the dermis, but how cell mechanics initiate pattern formation is not known. Here, we reconstitute the initiation of follicle patterning ex vivo using only freshly dissociated avian dermal cells and collagen. We find that contractile cells phys. rearrange the extracellular matrix (ECM) and that ECM rearrangement further aligns cells. This exchange transforms a mech. unlinked collective of dermal cells into a continuum, with coherent, long-range order. Combining theory with experiment, we show that this ordered cell-ECM layer behaves as an active contractile fluid that spontaneously forms regular patterns. Our study illustrates a role for mesenchymal dynamics in generating cell-level ordering and tissue-level patterning through a fluid instability-processes that may be at play across morphol. symmetry-breaking contexts.

Cell (Cambridge, MA, United States) published new progress about Aggregates. 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, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chen, Jinqin published the artcileA novel ω-conotoxin Bu8 inhibiting N-type voltage-gated calcium channels displays potent analgesic activity, HPLC of Formula: 21829-25-4, the main research area is conotoxin voltage gated calcium channel analgesic activity; Analgesic activity; Bu8; DIEA, diisopropylethylamine; ESI-MS, electrospray ionization-mass spectroscopy; Fmoc, N-(9-fluorenyl)methyloxy-carbonyl; HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; HOBt, 1-hydroxybenzotriazole; IC50, half-maximal inhibitory concentration; N-type calcium ion channel; RP-HPLC, reversed phase high-performance liquid chromatography; Structure–activity relationship; TFA, trifluoroacetic acid; ω-conotoxin.

A ω-Conotoxins inhibit N-type voltage-gated calcium (CaV2.2) channels and exhibit efficacy in attenuating neuropathic pain but have a low therapeutic index. Here, we synthesized and characterized a novel ω-conotoxin, Bu8 from Conus bullatus, which consists of 25 amino acid residues and three disulfide bridges. Bu8 selectively and potently inhibits depolarization-activated Ba2+ currents mediated by rat CaV2.2 expressed in HEK293T cells (IC50 = 89 nmol/L). Bu8 is two-fold more potent than ω-conotoxin MVIIA, a ω-conotoxin currently used for the treatment of severe chronic pain. It also displays potent analgesic activity in animal pain models of hot plate and acetic acid writhing but has fewer side effects on mouse motor function and lower toxicity in goldfish. Its lower side effects may be attributed to its faster binding rate and higher recovery ratios. The NMR structure demonstrates that Bu8 contains a small irregular triple β-strand. The structure-activity relationships of Bu8 Ala mutants and Bu8/MVIIA hybrid mutants demonstrate that the binding mode of CaV2.2 with the amino acid residues in loop 1 and loop 2 of Bu8 is different from that of MVIIA. This study characterizes a novel, more potent ω-conotoxin and provides new insights for designing CaV2.2 antagonists.

Acta Pharmaceutica Sinica B published new progress about Analgesics. 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, HPLC of Formula: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Bischoff, Angela published the artcileEffects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is nifedipine renal cardiovascular response neuropeptide Y anesthesia; Y1 receptor; Y5 receptor; blood pressure; diuresis; natriuresis; neuropeptide Y; nifedipine; renal blood flow.

Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y1, Y2 and Y5. While Y1 receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca2+ channels such as nifedipine, little is known about the role of such channels in Y5-mediated effects such as diuresis and natriuresis. Therefore, we explored whether nifedipine affects NPY-induced diuresis and natriuresis. After pre-treatment with nifedipine or vehicle, anesthetized rats received infusions or bolus injections of NPY. Infusion NPY (1μg/kg/min) increased diuresis and natriuresis, and this was attenuated by i.p. injection of nifedipine (3μg/kg). Concomitant decreases in heart rate and reductions of renal blood flow were not attenuated by nifedipine. Bolus injections of NPY (0.3, 1, 3, 10 and 30μg/kg) dose-dependently increased mean arterial pressure and renovascular vascular resistance; only the higher dose of nifedipine (100μg/kg/min i.v.) moderately inhibited these effects. We conclude that Y5-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y1-mediated renovascular effects. Whether this reflects a general sensitivity of Y5 receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.

Molecules published new progress about Anesthesia. 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, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gierten, Jakob published the artcileAutomated high-throughput heartbeat quantification in medaka and zebrafish embryos under physiological conditions, Related Products of pyridine-derivatives, the main research area is nifedipine cardioprotectant embryo heartbeat Oryzias Danio cardiovascular development.

Abstract: Accurate quantification of heartbeats in fish models is an important readout to study cardiovascular biol., disease states and pharmacol. However, dependence on anesthesia, laborious sample orientation or requirement for fluorescent reporters have hampered the use of high-throughput heartbeat anal. To overcome these limitations, we established an efficient screening assay employing automated label-free heart rate determination of randomly oriented, non-anesthetized medaka (Oryzias latipes) and zebrafish (Danio rerio) embryos in microtiter plates. Automatically acquired bright-field data feeds into an easy-to-use HeartBeat software with graphical user interface for automated quantification of heart rate and rhythm. Sensitivity of the assay was demonstrated by profiling heart rates during entire embryonic development. Our anal. revealed rapid adaptation of heart rates to temperature changes, which has implications for standardization of exptl. layout. The assay allows scoring of multiple embryos per well enabling a throughput of >500 embryos per 96-well plate. In a proof of principle screen for compound testing, we captured concentration-dependent effects of nifedipine and terfenadine over time. Our novel assay permits large-scale applications ranging from phenotypic screening, interrogation of gene functions to cardiovascular drug development.

Scientific Reports published new progress about Anesthesia. 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

Souza de Araujo, Guilherme Rodolfo published the artcileMicroemulsions formed by PPG-5-CETETH-20 at low concentrations for transdermal delivery of nifedipine: Structural and in vitro study, SDS of cas: 21829-25-4, the main research area is PPG5CETETH20 nifedipine microemulsion transdermal delivery skin permeation; Drug Delivery System(s); Microemulsion(s); Nanotechnology; Surfactant(s); Transdermal.

Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin. Colloids and Surfaces, B: Biointerfaces published new progress about Anisotropy. 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, SDS of cas: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Farrah, Tariq E. published the artcileEndothelin Receptor Antagonism Improves Lipid Profiles and Lowers PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in Patients With Chronic Kidney Disease, Computed Properties of 21829-25-4, the main research area is chronic kidney disease lipid PCSK9 endothelin receptor antagonism; atherosclerosis; cardiovascular disease; cholesterol; endothelins; triglycerides.

We assessed the effects of selective ETA antagonism on circulating lipids and PCSK9 (proprotein convertase subtilisin/kexin type 9) in CKD. This was a secondary anal. of a fully randomized, double-blind, 3-phase crossover study. Twenty-seven subjects with predialysis CKD on optimal cardio- and renoprotective treatment were randomly assigned to receive 6 wk dosing with placebo, the selective ETA receptor antagonist, sitaxentan, or long-acting nifedipine. We measured circulating lipids and PCSK9 at baseline and then after 3 and 6 wk. Baseline lipids and PCSK9 did not differ before each study phase. Whereas placebo and nifedipine had no effect on lipids, 6 wk of ETA antagonism significantly reduced total (-11±1%) and low-d. lipoprotein-associated (-20±3%) cholesterol, lipoprotein (a) (-16±2%) and triglycerides (-20±4%); high-d. lipoprotein-associated cholesterol increased (+14±2%), P<0.05 vs. baseline for all. Addnl., ETA receptor antagonism, but neither placebo nor nifedipine, reduced circulating PCSK9 (-19±2%; P<0.001 vs. baseline; P<0.05 vs. nifedipine and placebo). These effects were independent of statin use and changes in blood pressure or proteinuria. Selective ETA antagonism improves lipid profiles in optimally-managed patients with CKD, effects that may occur through a reduction in circulating PCSK9. ETA receptor antagonism offers a potentially novel strategy to reduce cardiovascular disease risk in CKD. Hypertension published new progress about Antagonism. 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, Computed Properties of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Langston-Cox, A. G. published the artcileSulforaphane Bioavailability and Effects on Blood Pressure in Women with Pregnancy Hypertension, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is sulforaphane bioavailability blood pressure pregnancy hypertension women; Antioxidant; Bioavailability; Broccoli; Preeclampsia; Sulforaphane.

Sulforaphane, an isothiocyanate found in cruciferous vegetables such as broccoli, shows promise as an adjuvant therapy for preeclampsia. To inform future clin. trials, we set out to determine the bioavailability of sulforaphane in non-pregnant and preeclamptic women. In six healthy female volunteers, we performed a crossover trial to compare the bioavailability of sulforaphane and metabolites afforded by activated and non-activated broccoli extract preparation We then undertook a dose escalation study of the activated broccoli extract in 12 women with pregnancy hypertension. In non-pregnant women, an equivalent dose of activated broccoli extract gave higher levels of sulforaphane and metabolites than a non-activated extract (p < 0.0001) and greater area under the curve (AUC) (3559 nM vs. 2172 nM, p = 0.03). Compared to non-pregnant women, in women with preeclampsia, the same dose of activated extract gave lower levels of total metabolites (p < 0.000) and AUC (3559 nM vs. 1653 nM, p = 0.007). Doubling the dose of the activated extract in women with preeclampsia doubled levels of sulforaphane and metabolites (p = 0.02) and AUC (1653 nM vs. 3333 nM, p = 0.02). In women with preeclampsia, activated broccoli extract was associated with modest decreases in diastolic blood pressure (p = 0.05) and circulating levels of sFlt-1 (p = 0.0002). A myrosinase-activated sulforaphane formulation affords better sulforaphane bioavailability than a non-activated formulation. Higher doses of sulforaphane are required to achieve likely EDs in pregnant women than in non-pregnant women. Sulforaphane may improve endothelial function and blood pressure in women with pregnancy hypertension. Reproductive Sciences published new progress about Biomarkers. 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, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Korkka, Iina published the artcileFunctional Voltage-Gated Calcium Channels Are Present in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium, Quality Control of 21829-25-4, the main research area is calcium channel embryonic stem cell retinal pigment epithelium disease; Patch-clamp; Phagocytosis; Retinal pigment epithelium; Stem cells; Vascular endothelial growth factor; Voltage-gated Ca2+ channels.

Retinal pigment epithelium (RPE) performs important functions for the maintenance of photoreceptors and vision. Malfunctions within the RPE are implicated in several retinal diseases for which transplantations of stem cell-derived RPE are promising treatment options. Their success, however, is largely dependent on the functionality of the transplanted cells. This requires correct cellular physiol., which is highly influenced by the various ion channels of RPE, including voltage-gated Ca2+ (CaV) channels. This study investigated the localization and functionality of CaV channels in human embryonic stem cell (hESC)-derived RPE. Whole-cell patch-clamp recordings from these cells revealed slowly inactivating L-type currents comparable to freshly isolated mouse RPE. Some hESC-RPE cells also carried fast transient T-type resembling currents. These findings were confirmed by immunostainings from both hESC- and mouse RPE that showed the presence of the L-type Ca2+ channels CaV1.2 and CaV1.3 as well as the T-type Ca2+ channels CaV3.1 and CaV3.2. The localization of the major subtype, CaV1.3, changed during hESC-RPE maturation co-localizing with pericentrin to the base of the primary cilium before reaching more homogeneous membrane localization comparable to mouse RPE. Based on functional assessment, the L-type Ca2+ channels participated in the regulation of vascular endothelial growth factor secretion as well as in the phagocytosis of photoreceptor outer segments in hESC-RPE. Overall, this study demonstrates that a functional machinery of voltage-gated Ca2+ channels is present in mature hESC-RPE, which is promising for the success of transplantation therapies.

Stem Cells Translational Medicine published new progress about Biomarkers. 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, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem