Tag: 238.2845

miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries was written by Mondejar-Parreno, Gema;Callejo, Maria;Barreira, Bianca;Morales-Cano, Daniel;Esquivel-Ruiz, Sergio;Moreno, Laura;Cogolludo, Angel;Perez-Vizcaino, Francisco. And the article was included in Journal of Physiology (Oxford, United Kingdom) in 2019.Product Details of 194413-58-6 This article mentions the following:

Key points : The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. Pulmonary artery smooth muscle cells from this animal model are more depolarized and show decreased expression and activity of voltage-dependent potassium channel (Kv)1.5. miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of the voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs are non-coding RNAs that regulate gene expression by binding to the 3′-untranslated region region of specific mRNAs. The present study aimed to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of the patch clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. MiR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. MiR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells. A luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O₂) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces pulmonary artery smooth muscle cell hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiol. role in PAH. In the experiment, the researchers used many compounds, for example, (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6Product Details of 194413-58-6).

(Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Product Details of 194413-58-6

Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Vegf signaling promotes vascular endothelial differentiation by modulating etv2 expression was written by Casie Chetty, Satish;Rost, Megan S.;Enriquez, Jacob Ryan;Schumacher, Jennifer A.;Baltrunaite, Kristina;Rossi, Andrea;Stainier, Didier Y. R.;Sumanas, Saulius. And the article was included in Developmental Biology (Amsterdam, Netherlands) in 2017.Related Products of 194413-58-6 This article mentions the following:

Vasculogenesis involves the differentiation of vascular endothelial progenitors de novo from undifferentiated mesoderm, their migration and coalescence to form the major embryonic vessels and the acquisition of arterial or venous identity. Vascular Endothelial Growth Factor (Vegf) signaling plays multiple roles during vascular development. However, its function during embryonic vasculogenesis has been controversial. Previous studies have implicated Vegf signaling in either regulating arteriovenous specification or overall vascular endothelial differentiation. To clarify the role of Vegf in embryonic vasculogenesis and identify its downstream targets, we used chem. inhibitors of Vegf receptor (Vegfr) signaling in zebrafish embryos as well as zebrafish genetic mutants. A high level of chem. inhibition of Vegfr signaling resulted in the reduction of overall vascular endothelial marker gene expression, including downregulation of both arterial and venous markers, ultimately leading to the apoptosis of vascular endothelial cells. In contrast, a low level of Vegfr inhibition specifically blocked arterial specification while the expression of venous markers appeared largely unaffected or increased. Inhibition of Vegfr signaling prior to the initiation of vasculogenesis reduced overall vascular endothelial differentiation, while inhibition of Vegfr signaling starting at mid-somitogenesis stages largely inhibited arterial specification. Conversely, Vegf overexpression resulted in the expansion of both arterial and pan-endothelial markers, while the expression of several venous-specific markers was downregulated. We further show that Vegf signaling affects overall endothelial differentiation by modulating the expression of the ETS transcription factor etv2/ etsrp. etv2 expression was downregulated in Vegfr- inhibited embryos, and expanded in Vegfaa-overexpressing embryos. Furthermore, vascular-specific overexpression of etv2 in Vegfr-inhibited embryos rescued defects in vascular endothelial differentiation. Similarly, vegfaa genetic mutants displayed a combination of the two phenotypes observed with chem. Vegfr inhibition: the expression of arterial and pan-endothelial markers including etv2 was downregulated while the expression of most venous markers was either expanded or unchanged. Based on these results we propose a revised model which explains the different phenotypes observed upon inhibition of Vegf signaling: low levels of Vegf signaling promote overall vascular endothelial differentiation and cell survival by upregulating etv2 expression, while high levels of Vegf signaling promote arterial and inhibit venous specification. In the experiment, the researchers used many compounds, for example, (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6Related Products of 194413-58-6).

(Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Related Products of 194413-58-6

Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Natural reversal of pulmonary vascular remodeling and right ventricular remodeling in SU5416/hypoxia-treated Sprague-Dawley rats was written by Zungu-Edmondson, Makhosazane;Shults, Nataliia V.;Melnyk, Oleksiy;Suzuki, Yuichiro J.. And the article was included in PLoS One in 2017.Safety of (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one This article mentions the following:

Pulmonary arterial hypertension (PAH) is a lethal disease and improved therapeutic strategies are needed. Increased pulmonary arterial pressure, due to vasoconstriction and vascular remodeling, causes right ventricle (RV) failure and death in patients. The treatment of Sprague-Dawley rats with SU5416 injection and exposure to chronic hypoxia for three weeks followed by maintenance in normoxia promote progressive and severe PAH with pathol. features that resemble human PAH. At 5-17 wk after the SU5416 injection, PAH is developed with pulmonary vascular remodeling as well as RV hypertrophy and fibrosis. The present study investigated subsequent events that occur in these PAH animals. At 35 wk after the SU5416 injection, rats still maintained high RV pressure, but pulmonary vascular remodeling was significantly reduced. Metabolomics anal. revealed that lungs of normal rats and rats from the 35-wk time point had different metabolomics profiles. Despite the maintenance of high RV pressure, fibrosis was resolved at 35-wk. Masson’s trichrome stain and Western blotting monitoring collagen 1 determined 12% fibrosis in the RV at 17-wk, and this was decreased to 5% at 35-wk. The level of myofibroblasts was elevated at 17-wk and normalized at 35-wk. These results suggest that biol. systems possess natural ways to resolve pulmonary and RV remodeling. The resolution of RV fibrosis appears to involve the reduction of myofibroblast- dependent collagen synthesis. Understanding these endogenous mechanisms should help improve therapeutic strategies to treat PAH and RV failure. In the experiment, the researchers used many compounds, for example, (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6Safety of (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one).

(Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Safety of (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one

Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries was written by Mondejar-Parreno, Gema;Callejo, Maria;Barreira, Bianca;Morales-Cano, Daniel;Esquivel-Ruiz, Sergio;Moreno, Laura;Cogolludo, Angel;Perez-Vizcaino, Francisco. And the article was included in Journal of Physiology (Oxford, United Kingdom) in 2019.Product Details of 194413-58-6 This article mentions the following:

Key points : The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. Pulmonary artery smooth muscle cells from this animal model are more depolarized and show decreased expression and activity of voltage-dependent potassium channel (Kv)1.5. miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of the voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs are non-coding RNAs that regulate gene expression by binding to the 3′-untranslated region region of specific mRNAs. The present study aimed to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of the patch clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. MiR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. MiR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells. A luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O₂) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces pulmonary artery smooth muscle cell hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiol. role in PAH. In the experiment, the researchers used many compounds, for example, (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6Product Details of 194413-58-6).

(Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Product Details of 194413-58-6

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Vegf signaling promotes vascular endothelial differentiation by modulating etv2 expression was written by Casie Chetty, Satish;Rost, Megan S.;Enriquez, Jacob Ryan;Schumacher, Jennifer A.;Baltrunaite, Kristina;Rossi, Andrea;Stainier, Didier Y. R.;Sumanas, Saulius. And the article was included in Developmental Biology (Amsterdam, Netherlands) in 2017.Related Products of 194413-58-6 This article mentions the following:

Vasculogenesis involves the differentiation of vascular endothelial progenitors de novo from undifferentiated mesoderm, their migration and coalescence to form the major embryonic vessels and the acquisition of arterial or venous identity. Vascular Endothelial Growth Factor (Vegf) signaling plays multiple roles during vascular development. However, its function during embryonic vasculogenesis has been controversial. Previous studies have implicated Vegf signaling in either regulating arteriovenous specification or overall vascular endothelial differentiation. To clarify the role of Vegf in embryonic vasculogenesis and identify its downstream targets, we used chem. inhibitors of Vegf receptor (Vegfr) signaling in zebrafish embryos as well as zebrafish genetic mutants. A high level of chem. inhibition of Vegfr signaling resulted in the reduction of overall vascular endothelial marker gene expression, including downregulation of both arterial and venous markers, ultimately leading to the apoptosis of vascular endothelial cells. In contrast, a low level of Vegfr inhibition specifically blocked arterial specification while the expression of venous markers appeared largely unaffected or increased. Inhibition of Vegfr signaling prior to the initiation of vasculogenesis reduced overall vascular endothelial differentiation, while inhibition of Vegfr signaling starting at mid-somitogenesis stages largely inhibited arterial specification. Conversely, Vegf overexpression resulted in the expansion of both arterial and pan-endothelial markers, while the expression of several venous-specific markers was downregulated. We further show that Vegf signaling affects overall endothelial differentiation by modulating the expression of the ETS transcription factor etv2/ etsrp. etv2 expression was downregulated in Vegfr- inhibited embryos, and expanded in Vegfaa-overexpressing embryos. Furthermore, vascular-specific overexpression of etv2 in Vegfr-inhibited embryos rescued defects in vascular endothelial differentiation. Similarly, vegfaa genetic mutants displayed a combination of the two phenotypes observed with chem. Vegfr inhibition: the expression of arterial and pan-endothelial markers including etv2 was downregulated while the expression of most venous markers was either expanded or unchanged. Based on these results we propose a revised model which explains the different phenotypes observed upon inhibition of Vegf signaling: low levels of Vegf signaling promote overall vascular endothelial differentiation and cell survival by upregulating etv2 expression, while high levels of Vegf signaling promote arterial and inhibit venous specification. In the experiment, the researchers used many compounds, for example, (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6Related Products of 194413-58-6).

(Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Related Products of 194413-58-6

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Natural reversal of pulmonary vascular remodeling and right ventricular remodeling in SU5416/hypoxia-treated Sprague-Dawley rats was written by Zungu-Edmondson, Makhosazane;Shults, Nataliia V.;Melnyk, Oleksiy;Suzuki, Yuichiro J.. And the article was included in PLoS One in 2017.Safety of (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one This article mentions the following:

Pulmonary arterial hypertension (PAH) is a lethal disease and improved therapeutic strategies are needed. Increased pulmonary arterial pressure, due to vasoconstriction and vascular remodeling, causes right ventricle (RV) failure and death in patients. The treatment of Sprague-Dawley rats with SU5416 injection and exposure to chronic hypoxia for three weeks followed by maintenance in normoxia promote progressive and severe PAH with pathol. features that resemble human PAH. At 5-17 wk after the SU5416 injection, PAH is developed with pulmonary vascular remodeling as well as RV hypertrophy and fibrosis. The present study investigated subsequent events that occur in these PAH animals. At 35 wk after the SU5416 injection, rats still maintained high RV pressure, but pulmonary vascular remodeling was significantly reduced. Metabolomics anal. revealed that lungs of normal rats and rats from the 35-wk time point had different metabolomics profiles. Despite the maintenance of high RV pressure, fibrosis was resolved at 35-wk. Masson’s trichrome stain and Western blotting monitoring collagen 1 determined 12% fibrosis in the RV at 17-wk, and this was decreased to 5% at 35-wk. The level of myofibroblasts was elevated at 17-wk and normalized at 35-wk. These results suggest that biol. systems possess natural ways to resolve pulmonary and RV remodeling. The resolution of RV fibrosis appears to involve the reduction of myofibroblast- dependent collagen synthesis. Understanding these endogenous mechanisms should help improve therapeutic strategies to treat PAH and RV failure. In the experiment, the researchers used many compounds, for example, (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6Safety of (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one).

(Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one (cas: 194413-58-6) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Safety of (Z)-3-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles