Day: November 30, 2022

Theopold, Ulrich published the artcileTRP channels, the missing link for Ca2+ tuning by a unicellular eukaryotic parasite?, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is calcium tuning TRP channel unicellular eukaryotic parasite; Apicomplexa; Host-pathogen; Protozoa; TRP channel; Toxoplasma gondii; VDCC.

Sensing and responding to changes in the cellular environments are essential for the diverse family of Apicomplexan parasites, which undergo complex life cycles comprised of both extracellular and obligate intracellular stages. Despite evidence of paramount roles for Ca2+, the mol. players behind how parasites sense Ca2+ and initiate Ca2+ signaling cascades have remained enigmatic. In a recent publication, Marquez-Nogueras et al., identify a transient receptor potential (TRP)-like channel in Toxoplasma gondii and show its implication in the crucial processes of parasite invasion and egress from host cells.

Cell Calcium published new progress about Cell cycle. 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

Lazrak, Ahmed published the artcileUpregulation of airway smooth muscle calcium-sensing receptor by low-molecular-weight hyaluronan, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is hyaluronan airway smooth muscle calcium sensing receptor upregulation; airway hyperresponsiveness; calcium-sensing receptor; diltiazem; halogens; human airway smooth muscle cells; membrane potential; nifedipine.

We investigated the mechanisms involved in the development of airway hyperresponsiveness (AHR) following exposure of mice to halogens. Male mice (C57BL/6; 20-25 g) exposed to either bromine (Br2) or Cl2 (600 or 400 ppm, resp., for 30 min) developed AHR 24 h after exposure. Nifedipine (5 mg/kg body wt; an L-type calcium channel blocker), administered s.c. after Br2 or Cl2 exposure, produced higher AHR compared with Br2 or Cl2 alone. In contrast, diltiazem (5 mg/kg body wt; a nondihydropyridine L-type calcium channel blocker) decreased AHR to control (air) values. Exposure of immortalized human airway smooth muscle cells (hASMC) to Br2 resulted in membrane potential depolarization (Vm Air: 62 ± 3 mV; 3 h post Br2:-45 ± 5 mV; means ± 1 SE; P < 0.001), increased intracellular [Ca2+]i, and increased expression of the calcium-sensing receptor (Ca-SR) protein. Treatment of hASMC with a siRNA against Ca-SR significantly inhibited the Br2 and nifedipine-induced Vm depolarization and [Ca2+]i increase. Intranasal administration of an antagonist to Ca-SR in mice post-exposure to Br2 reversed the effects of Br2 and nifedipine on AHR. Incubation of hASMC with low-mol.-weight hyaluronan (LMW-HA), generated by exposing high-mol.-weight hyaluronan (HMW-HA) to Br2, caused Vm depolarization, [Ca2+]i increase, and Ca-SR expression to a similar extent as exposure to Br2 and Cl2. The addition of HMW-HA to cells or mice exposed to Br2, Cl2, or LMW-HA reversed these effects in-vitro and improved AHR in-vivo. We conclude that detrimental effects of halogen exposure on AHR are mediated via activation of the Ca-SR by LMW-HA. American Journal of Physiology published new progress about Homo sapiens. 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

Feng, Xueqin published the artcilePrenatal High-Sucrose Diet Induced Vascular Dysfunction in Thoracic Artery of Fetal Offspring, Category: pyridine-derivatives, the main research area is At1 alpha beta vascular injury; L-type calcium channels; fetal offspring; inositol 1,4,5-trisphosphate receptors; prenatal high-sucrose; vascular dysfunction.

Maternal nutrition during pregnancy is related to intrauterine fetal development. The authors previous work reports that prenatal high sucrose (HS) diet impaired micro-vascular functions in postnatal offspring. It is unclear whether/how prenatal HS causes vascular injury during fetal life. Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Pregnant HS increases maternal waight before delivery. Fetal thoracic aorta is seperated for exprements. Angiotensin II (AII)-stimulated vascular contraction of fetal thoracic arteries in HS group is greater, which mainly results from the enhanced AT1 receptor (AT1R) function and the downstream signaling. Nifedipine significantly increases vascular tension in HS group, indicating that the L-type calcium channels (LTCCs) function is strengthened. 2-Aminoethyl diphenylborinate (2-APB), inositol 1,4,5-trisphosphate receptors (IP3Rs) inhibitor, increases vascular tension induced by AII in HS group and ryanodine receptors-sensitive vascular tone shows no difference in the two groups, which suggested that the activity of IP3Rs-operated calcium channels is increased. These findings suggest that prenatal HS induces vascular dysfunction of thoracic arteries in fetal offspring by enhancing AT1R, LTCCs function and IP3Rs-associated calcium channels, providing new information regarding the impact of prenatal HS on the functional development of fetal vascular systems.

Molecular Nutrition & Food Research published new progress about Angiotensin receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Qian published the artcileAzithromycin inhibits muscarinic 2 receptor-activated and voltage-activated Ca2+ permeant ion channels and Ca2+ sensitization, relaxing airway smooth muscle contraction, Synthetic Route of 21829-25-4, the main research area is asthma chronic obstructive pulmonary disease muscarinic 2 receptor azithromycin; airway smooth muscle; asthma; azithromycin; chronic obstructive pulmonary disease; ion channels; relaxation.

The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch-clamp techniques. AZM completely inhibited acetylcholine (ACH)-induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L-type voltage-dependent Ca2+ channels (LVDCCs)), Pyr3 (selective inhibitor of TRPC3 and/or STIM/Orai channels, which are nonselective cation channels (NSCCs)), and Y-27632 (selective inhibitor of Rho-associated kinase (ROCK)). Moreover, LVDCC- and NSCC-mediated currents were inhibited by AZM, and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca2+ permeant ion channels, M2 receptors, and TRPC3 and/or STIM/Orai, which decreased cytosolic Ca2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD.

Clinical and Experimental Pharmacology and Physiology published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (Orai). 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, Synthetic Route of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Brinkmann, Joscha published the artcileSolubility of Pharmaceutical Ingredients in Natural Edible Oils, COA of Formula: C18H19Cl2NO4, the main research area is solubility pharmaceutical ingredient edible oil; PC-SAFT; lipid-based drug delivery systems; oils; solubility.

Natural edible oils (NEOs) are common excipients for lipid-based formulations. Many of them are complex mixtures comprising hundreds of different triglycerides (TGs). One major challenge in developing lipid-based formulations is the variety in NEO compositions affecting the solubility of active pharmaceutical ingredients. In this work, solubilities of indomethacin (IND), ibuprofen (IBU), and fenofibrate (FFB) in soybean oil and in coconut oil were measured via differential scanning calorimetry, high-performance liquid chromatog., and Raman spectroscopy. Furthermore, this work proposes an approach that mimics NEOs using one key TG and models the API solubilities in these NEOs based on perturbed-chain statistical associating fluid theory (PC-SAFT). Key TGs were determined using the 1,2,3-random hypothesis, and PC-SAFT parameters were estimated via a group-contribution method. Using the proposed approach, the solubility of IBU and FFB was modeled in soybean oil and coconut oil. Furthermore, the solubilities of five more APIs (IND, cinnarizine, naproxen, griseofulvin, and felodipine) were modeled in soybean oil. All modeling results were found in very good agreement with the exptl. data. The influence of different NEO kinds on API solubility was examined by comparing FFB and IBU solubilities in soybean oil and refined coconut oil. PC-SAFT was thus found to allow assessing the batch-to-batch consistency of NEO batches in silico.

Molecular Pharmaceutics published new progress about Differential scanning calorimetry. 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, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ju, Yanqin published the artcileTranscriptional analysis reveals key genes in the pathogenesis of nifedipine-induced gingival overgrowth, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is nifedipine inflammatory cytokines glycans.

Background. Nifedipine-induced gingival overgrowth (NGO) is a multifactorial pathogenesis with increased extracellular matrix including collagen and glycans, inflammatory cytokines, and phenotype changes of fibroblasts. However, the mol. etiol. of NGO is not well understood. The objective of this study is to investigate the key genes in the pathogenesis of NGO. Methods. In this study, we examined the proliferation and migration abilities of fibroblasts derived from patients with chronic periodontitis, nifedipine nonresponder gingival overgrowth, gingival overgrowth caused by nifedipine, and healthy normal gingiva. We conducted RNA-Seq on these four groups of fibroblasts and analyzed the differentially expressed genes (DEGs). Results. Fibroblasts derived from NGO patients had higher proliferation and migration abilities than those of the other groups. Protein-protein interaction network anal. indicated that TGFB2, ITGA8, ITGA11, FGF5, PLA2G4D, PLA2G2F, PTGS1, CSF1, LPAR1, CCL3, and NKX3-1 are involved in the development of NGO. These factors are related to the arachidonic acid metabolism and PI3K/AKT signaling pathways. Conclusion. Transcriptional gene expression anal. identified a number of DEGs that might be functionally related to gingival overgrowth induced by nifedipine. Our study provides important information on the mol. mechanism underlying nifedipine-induced gingival overgrowth.

Analytical Cellular Pathology published new progress about Animal gene, CSF1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Morin, Alexander published the artcileNilvadipine suppresses inflammation via inhibition of P-SYK and restores spatial memory deficits in a mouse model of repetitive mild TBI, Product Details of C17H18N2O6, the main research area is Nilvadipine neuroprotective agent mild traumatic brain injury.

Repeated exposure to mild TBI (mTBI) has been linked to an increased risk of Alzheimers disease (AD), chronic traumatic encephalopathy (CTE) and other neurodegenerative diseases. Some pathol. features typically observed in AD have been found in postmortem brains of TBI and CTE, hence treatments tested for AD have a potential to be effective against r-mTBI outcomes. Neuroinflammation may present a possible answer due to its central role both in acute brain injury and in chronic degenerative-like disorders. Our previous studies have shown that drug nilvadipine, acting as an inhibitor of spleen tyrosine kinase (SYK), is effective at reducing inflammation, tau hyperphosphorylation and amyloid production in AD mouse models. To demonstrate the effect of nilvadipine in the absence of age-related variables, we introduced the same treatment to young r-mTBI mice. We further investigate therapeutic mechanisms of nilvadipine using its racemic properties. Both enantiomers, (+)-nilvadipine and (-)-nilvadipine, can lower SYK activity, whereas (+)-nilvadipine is also a potent L-type calcium channel blocker (CCB) and shown to be anti-hypertensive. All r-mTBI mice exhibited increased neuroinflammation and impaired cognitive performance and motor functions. Treatment with racemic nilvadipine mitigated the TBI-induced inflammatory response and significantly improved spatial memory, whereas (-)-enantiomer decreased microgliosis and improved spatial memory but failed to reduce the astroglial response to as much as the racemate. These results suggest the therapeutic potential of SYK inhibition that is enhanced when combined with the CCB effect, which indicate a therapeutic advantage of multi-action drugs for r-mTBI.

Acta Neuropathologica Communications published new progress about Alzheimer disease. 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, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Puro, Donald G. published the artcileImpact of P2X7 Purinoceptors on Goblet Cell Function: Implications for Dry Eye, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is conjunctiva single goblet cell exocytosis temporal resolution membrane capacitance; P2X7 receptor/channels; conjunctival goblet cells; exocytosis; membrane capacitance.

By providing âˆ?70% of the eye’s refractive power, the preocular tear film is essential for optimal vision. However, its integrity is often jeopardized by environmental and pathol. conditions that accelerate evaporation and cause sight-impairing dry eye. A key adaptive response to evaporation-induced tear film hyperosmolarity is the reflex-triggered release of tear-stabilizing mucin from conjunctival goblet cells. Here, we review progress in elucidating the roles of ion channels in mediating this important exocytotic response. Much is now known about the modulatory impact of ATP-sensitive potassium channels, nonspecific cation channels and voltage-gated calcium channels. Recently, we discovered that during unremitting extracellular hyperosmolarity, P2X7 receptor/channels also become activated and markedly impair goblet cell viability. However, our understanding of possible adaptive benefits of this P2X7 activation remains limited. In the present study, we utilized high-temporal resolution membrane capacitance measurements to monitor the exocytotic activity of single goblet cells located in freshly excised rat conjunctiva. We now report that activation of P2X7 purinoceptors boosts neural-evoked exocytosis and accelerates replenishment of mucin-filled granules after exocytotic depletion. Thus, P2X7 activation exerts a yin-yang effect on conjunctival goblet cells: the high-gain benefit of enhancing the supply of tear-stabilizing mucin is implemented at the high-risk of endangering goblet cell survival.

International Journal of Molecular Sciences published new progress about Cell survival. 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

Nguyen, Viet D. published the artcileRapid and Chemodivergent Synthesis of N-Heterocyclic Sulfones and Sulfides: Mechanistic and Computational Details of the Persulfate-Initiated Catalysis, Quality Control of 24484-93-3, the main research area is azaheterocyclyl sulfone sulfide chemoselective preparation; persulfate initiated sulfonylation azaheterocyclyl halide sulfinate biphasic solvent; mechanism persulfate initiated sulfonylation azaheterocyclyl halide sulfinate; hydroxymethylsulfinate mediated sulfonylation reduction azaheterocyclyl halide initiated persulfate; transition state structure kinetics sulfonylation azaheterocyclyl halide sulfinate.

Aromatic nitrogen heterocyclyl halides underwent sulfonylation reactions with sodium sulfinates mediated by sodium or ammonium persulfates in biphasic aqueous/organic solvent mixtures to yield azaheterocyclyl sulfones at ambient temperature; the products can be isolated by filtration. Reaction of aromatic nitrogen heterocyclyl halides with sodium hydroxymethylsulfinate mediated by sodium persulfate yielded either sym. azaheterocyclyl sulfones or sym. azaheterocyclyl sulfides, depending on the amount (1.2 or 3-4 equiv) of sulfinate used. Study of the mechanism of persulfate-mediated sulfonylation by DFT calculations and kinetic studies indicates that persulfate reacts with sulfinates to form sulfinic acids by a nonradical mechanism which accelerates the sulfonylation, particularly in water; the sulfonylation and reduction of azaheterocycles with sodium hydroxymethylsulfinate is proposed to act through a radical mechanism. The structures of seventeen of the products were determined by X-ray crystallog.

ACS Catalysis published new progress about Aromatic nitrogen heterocycles Role: RCT (Reactant), RACT (Reactant or Reagent) (halo-). 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Quality Control of 24484-93-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lee, A. Reum published the artcileLercanidipine synergistically enhances bortezomib cytotoxicity in cancer cells via enhanced endoplasmic reticulum stress and mitochondrial Ca2+ overload, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is breast cancer lercanidipine bortezomib cytotoxicity endoplasmic reticulum mitochondria calcium; ER stress; bortezomib; lercanidipine; mitochondrial Ca2+ overload; paraptosis.

The proteasome inhibitor (PI), bortezomib (Btz), is effective in treating multiple myeloma and mantle cell lymphoma, but not solid tumors. In this study, we show for the first time that lercanidipine (Ler), an antihypertensive drug, enhances the cytotoxicity of various PIs, including Btz, carfilzomib, and ixazomib, in many solid tumor cell lines by inducing paraptosis, which is accompanied by severe vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. We found that Ler potentiates Btz-mediated ER stress and ER dilation, possibly due to misfolded protein accumulation, in MDA-MB 435S cells. In addition, the combination of Btz and Ler triggers mitochondrial Ca2+ overload, critically contributing to mitochondrial dilation and subsequent paraptotic events, including mitochondrial membrane potential loss and ER dilation. Taken together, our results suggest that a combined regimen of PI and Ler may effectively kill cancer cells via structural and functional perturbations of the ER and mitochondria.

International Journal of Molecular Sciences published new progress about Antitumor 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, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem