Cisplatin−DNA Cross-link Models with an Unusual Type of Chirality-Neutral Chelate Amine Carrier Ligand,N,N‘-Dimethylpiperazine (Me2ppz):  Me2ppzPt(guanosine monophosphate)2Adducts That Exhibit Novel Properties

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

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Effects of Porphyra tenera Extracts on Formation of Collagen Cross-link in Ovariectomized Rats

Journal of the Korean Society of Food Science and Nutrition ◽

10.3746/jkfn.2004.33.2.324 ◽

2004 ◽

Vol 33 (2) ◽

pp. 324-330 ◽

Cited By ~ 1

Keyword(s):

Ovariectomized Rats ◽

Cross Link ◽

Porphyra Tenera

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Soluble Guanylate Cyclase Stimulators and Activators: Where are We and Where to Go?

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190730110600 ◽

2019 ◽

Vol 19 (18) ◽

pp. 1544-1557 ◽

Cited By ~ 6

Author(s):

Sijia Xiao ◽

Qianbin Li ◽

Liqing Hu ◽

Zutao Yu ◽

Jie Yang ◽

...

Keyword(s):

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Muscle Relaxation ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Smooth Muscle Relaxation ◽

Secondary Messenger ◽

Physiological Processes ◽

Cgmp Pathway ◽

Preclinical And Clinical Studies

Soluble Guanylate Cyclase (sGC) is the intracellular receptor of Nitric Oxide (NO). The activation of sGC results in the conversion of Guanosine Triphosphate (GTP) to the secondary messenger cyclic Guanosine Monophosphate (cGMP). cGMP modulates a series of downstream cascades through activating a variety of effectors, such as Phosphodiesterase (PDE), Protein Kinase G (PKG) and Cyclic Nucleotide-Gated Ion Channels (CNG). NO-sGC-cGMP pathway plays significant roles in various physiological processes, including platelet aggregation, smooth muscle relaxation and neurotransmitter delivery. With the approval of an sGC stimulator Riociguat for the treatment of Pulmonary Arterial Hypertension (PAH), the enthusiasm in the discovery of sGC modulators continues for broad clinical applications. Notably, through activating the NO-sGC-cGMP pathway, sGC stimulator and activator potentiate for the treatment of various diseases, such as PAH, Heart Failure (HF), Diabetic Nephropathy (DN), Systemic Sclerosis (SS), fibrosis as well as other diseases including Sickle Cell Disease (SCD) and Central Nervous System (CNS) disease. Here, we review the preclinical and clinical studies of sGC stimulator and activator in recent years and prospect for the development of sGC modulators in the near future.

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Boron nitride for modification of rubber based on isoprene elastomer

Voprosy Materialovedeniya ◽

10.22349/1994-6716-2019-100-4-105-112 ◽

2020 ◽

pp. 105-112

Author(s):

K. S. Zhansakova ◽

E. N. Eremin ◽

G. S. Russkikh ◽

O. V. Kropotin

Keyword(s):

Mechanical Properties ◽

Boron Nitride ◽

Gradual Increase ◽

Physical And Mechanical Properties ◽

Curing Time ◽

Cross Link ◽

Start Time ◽

Link Density ◽

Cross Link Density ◽

Isoprene Rubber

The work studies vulcanization characteristics of elastomers based on isoprene rubber filled with carbon black N330 and boron nitride (BN). The influence of the boron nitride (BN) concentration on technological, dynamic, physical and mechanical properties of elastomers has been researched. The application of boron nitride for producing rubber with good properties has been considered. With a gradual increase of the inert filler BN concentration up to 35%, a decrease in the curing rate by 33% and polymer cross-link density by 26% is observed. Moreover, the start time of vulcanization increases by almost 300%, the optimal curing time by 200%.

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The cGMP-Dependent Protein Kinase 2 Contributes to Cone Photoreceptor Degeneration in the Cnga3-Deficient Mouse Model of Achromatopsia

International Journal of Molecular Sciences ◽

10.3390/ijms22010052 ◽

2020 ◽

Vol 22 (1) ◽

pp. 52

Author(s):

Mirja Koch ◽

Constanze Scheel ◽

Hongwei Ma ◽

Fan Yang ◽

Michael Stadlmeier ◽

...

Keyword(s):

Protein Kinase ◽

Mouse Model ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Cone Photoreceptor ◽

Photoreceptor Degeneration ◽

Dependent Protein Kinase ◽

Genetic Ablation ◽

Cgmp Dependent Protein Kinase ◽

Dependent Protein

Mutations in the CNGA3 gene, which encodes the A subunit of the cyclic guanosine monophosphate (cGMP)-gated cation channel in cone photoreceptor outer segments, cause total colour blindness, also referred to as achromatopsia. Cones lacking this channel protein are non-functional, accumulate high levels of the second messenger cGMP and degenerate over time after induction of ER stress. The cell death mechanisms that lead to loss of affected cones are only partially understood. Here, we explored the disease mechanisms in the Cnga3 knockout (KO) mouse model of achromatopsia. We found that another important effector of cGMP, the cGMP-dependent protein kinase 2 (Prkg2) is crucially involved in cGMP cytotoxicity of cones in Cnga3 KO mice. Virus-mediated knockdown or genetic ablation of Prkg2 in Cnga3 KO mice counteracted degeneration and preserved the number of cones. Analysis of markers of endoplasmic reticulum stress and unfolded protein response confirmed that induction of these processes in Cnga3 KO cones also depends on Prkg2. In conclusion, we identified Prkg2 as a novel key mediator of cone photoreceptor degeneration in achromatopsia. Our data suggest that this cGMP mediator could be a novel pharmacological target for future neuroprotective therapies.

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