Journal: PLoS ONE

Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

doi: 10.1371/journal.pone.0199927

Figure Lengend Snippet: ( A ) H & E stained lung histology. Hyperoxia exposure in the presence of placebo decreased radial alveolar count (RAC) ( B ) and increased mean linear intercept (MLI) ( C ) as compared with normoxia. Administration of riociguat increased RAC and decreased MLI during hyperoxia. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 100 μm.

Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

Techniques: Staining

Journal: PLoS ONE

Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

doi: 10.1371/journal.pone.0199927

Figure Lengend Snippet: ( A ) Immunofluorescence staining for von-Willebrand factor (vWF) (green signal). Vascular density (VD) was determined by counting vWF-positive vessels (<50 μm in diameter) on 10 random high-power field (HPF) images from each lung section. ( B ) Hyperoxia exposure in the presence of placebo significantly decreased VD as compared with normoxia group. Administration of riociguat increased VD in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 50 μm.

Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

Techniques: Immunofluorescence, Staining

Journal: PLoS ONE

Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

doi: 10.1371/journal.pone.0199927

Figure Lengend Snippet: ( A , C ) Double immunofluorescence staining for vWF (green signal) and α-SMA (red signal) plus DAPI nuclear stain (blue signal). ( B ) Hyperoxia exposure in the presence of placebo increased muscularization of peripheral pulmonary vessels (<50 μm in diameter) as compared with normoxia group (red arrow). Administration of riociguat decreased muscularized vessels in hyperoxia exposed lungs. ( D ) Hyperoxia increased medial wall thickness (MWT) in presence of placebo as compared with normoxia group. Riociguat administration significantly decreased MWT in hyperoxia group. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). Scale bar: 50 μm. ( E ) Double immunofluorescence staining with Ki67 (red arrow) and α-SMA (green signal) plus DAPI nuclear staining (blue signal). ( F ) Hyperoxia exposure in the presence of placebo increased vascular proliferation as compared with normoxia group. Administration of riociguat decreased vascular proliferation. *** P < 0.001 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). ( G ) CTGF gene expression was up-regulated by hyperoxia and it was down-regulated by riociguat. * P < 0.05 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo (n = 6/group). ( H ) Representative Western blots of CTGF and β-actin. ( I ). Expression of CTGF was increased by hyperoxia, while administration of riociguat decreased CTGF expression in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo (n = 6/group). RA: room air, normaxia; O 2 : hyperoxia; PL: placebo; Rio: riociguat.

Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

Techniques: Double Immunofluorescence Staining, Staining, Gene Expression, Western Blot, Expressing

Journal: PLoS ONE

Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

doi: 10.1371/journal.pone.0199927

Figure Lengend Snippet: ( A ) Right ventricular systolic pressure (RVSP) was significantly increased in the hyperoxia + placebo treated group as compared with normoxia group. Riociguat administration significantly decreased RVSP during hyperoxia. *** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo (n = 6/group). ( B ) Right ventricular hypertrophy (RVH), also known as the Fulton’s index, was determined by the weight ratio of right ventricle (RV) to left ventricle + septum (LV + S). Hyperoxia exposed animals in the presence of placebo showed significant RVH as compared with normoxia group. Administration of riociguat decreased RVH in hyperoxia exposed lungs. *** P < 0.001 compared with normoxia; ++ P < 0.01 compared with hyperoxia + placebo (n = 6/group).

Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

Techniques:

Journal: PLoS ONE

Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

doi: 10.1371/journal.pone.0199927

Figure Lengend Snippet: ( A ) Immunostaining for Mac-3, a macrophage marker. ( B ) The alveolar airspace macrophage population was increased by hyperoxia exposure as compared to normoxia. Administration of riociguat decreased macrophage count during hyperoxia. *** P < 0.001 compared with normoxia; ++ P < 0.01 compared with hyperoxia + placebo (n = 6/group). ( C ) Immunostaining for the M1 marker, inducible nitric oxide synthase (iNOS), and M2 markers, chitinase 3-like 3 (Ym1) and resistin-like molecule alpha (RELM-α) showed that in hyperoxia plus placebo lungs, both M1 and M2 polarized macrophages were detected. But, treatment with riociguat decreased only M1 macrophages in hyperoxia-exposed lungs. ( D ) Representative Western blots for NLRP-1, active caspase-1 and active IL-1β. Administration of riociguat decreased hyperoxia-induced lung expression of ( E ) NLRP-1 (*** P < 0.001 compared with normoxia; + P < 0.05 compared with hyperoxia + placebo), ( F ) active caspase-1 (*** P < 0.001 compared with normoxia; ++ P < 0.05 compared with hyperoxia + placebo), and ( G ) active IL-1β (* P < 0.05 compared with normoxia; +++ P < 0.001 compared with hyperoxia + placebo). RA: room air, normoxia; O 2 : hyperoxia; PL: placebo; Rio: riociguat.

Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

Techniques: Immunostaining, Marker, Western Blot, Expressing

Journal: PLoS ONE

Article Title: Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

doi: 10.1371/journal.pone.0199927

Figure Lengend Snippet: Riociguat significantly increased cGMP concentration in hyperoxia-exposed rats as compared with placebo treated hyperoxic rats. * P < 0.05 compared with hyperoxia + placebo (n = 4/group).

Article Snippet: Riociguat was obtained from Medchemexpress (Monmouth Junction, NJ).

Techniques: Concentration Assay

Journal: Hepatology (Baltimore, Md.)

Article Title: Single‐Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell–Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice

doi: 10.1002/hep.31987

Figure Lengend Snippet: Differential responses of Riociguat treatment in CCL ‐ and BDL‐induced liver fibrosis. (A) The correlation of the expression of Gucy1a1 and Gucy1b1 in HSCs and PFs. (B) The expression of Gucy1a1 and Gucy1b1 in individual HSCs and portal fibroblasts were overlaid on the UMAP. Dot lines outline the different subclusters according to Figure B. (C) Schematic overview of the experimental design. CCL was injected twice a week for 3 weeks and Riociguat (10 mg/kg body weight) was administered twice a day by oral gavage. Representative images of liver sections from control, CCL ‐, and CCL + Riociguat‐treated mice were stained with sirius red to show the collagen deposit. (D) Sirius red positive area, hydroxyproline concentration, and serum ALT and AST enzymatic activity in the livers of control, CCL ‐, and CCL + Riociguat‐treated mice were quantitated (Corn oil + vehicle, n = 4; CCL + vehicle, n = 6; CCL + Riociguat, n = 6). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001. (E) Schematic overview of the experimental design of the BDL experiment. Vehicle or Riociguat (10 mg/kg body weight) was administered twice a day for 10 days. Representative images of liver sections of vehicle‐ or Riociguat‐treated BDL mice were stained with sirius red. (F) Quantification of sirius red positive area, hydroxyproline concentration, ALT and AST enzymatic activity, and total bilirubin (T‐BIL) concentration in the serum of vehicle‐ or Riociguat‐treated BDL mice (sham + vehicle, n = 4; BDL + vehicle, n = 6; BDL + Riociguat, n = 5). Statistical analyses were performed using one‐way ANOVA with Tukey HSD test. ns: not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001.

Article Snippet: For treatment, mice received Riociguat (Selleck, S8135; 10 mg/kg body weight) or vehicle control twice a day via oral gavage.

Techniques: Expressing, Injection, Control, Staining, Concentration Assay, Activity Assay

Journal: PLoS ONE

Article Title: Effects of Stimulation of Soluble Guanylate Cyclase on Diabetic Nephropathy in Diabetic eNOS Knockout Mice on Top of Angiotensin II Receptor Blockade

doi: 10.1371/journal.pone.0042623

Figure Lengend Snippet: Experimental progress of blood pressure and blood glucose in diabetic eNOS knockout mice treated with riociguat (3 mg/kg/d), telmisartan (1 mg/kg/d), both (3 mg/kg/d and 1 mg/kg/d) or vehicle.

Article Snippet: Riociguat [BAY 63-2521; Methyl 2-[1-2(-fluorobenzyl)-1 H -pyrazolo[3,4- b ]pyridin-3-yl]-4,6—diaminopyrimidin-5-ylmethylcarbamat] was synthesized by Bayer Pharma AG as described and dissolved in Transcutol®/Cremophor®/water (10/20/70).

Techniques: Knock-Out

Journal: PLoS ONE

Article Title: Effects of Stimulation of Soluble Guanylate Cyclase on Diabetic Nephropathy in Diabetic eNOS Knockout Mice on Top of Angiotensin II Receptor Blockade

doi: 10.1371/journal.pone.0042623

Figure Lengend Snippet: Final urinary albumin as well as organ weights and histology of diabetic mice after 11 weeks of treatment with riociguat (3 mg/kg/d), telmisartan (1 mg/kg/d), riociguat and telmisartan (3 mg/kg/d and 1 mg/kg/d) or vehicle and of non-diabetic control mice, respectively.

Article Snippet: Riociguat [BAY 63-2521; Methyl 2-[1-2(-fluorobenzyl)-1 H -pyrazolo[3,4- b ]pyridin-3-yl]-4,6—diaminopyrimidin-5-ylmethylcarbamat] was synthesized by Bayer Pharma AG as described and dissolved in Transcutol®/Cremophor®/water (10/20/70).

Techniques: Control

Journal: Pharmacy and Therapeutics

Article Title: Riociguat (Adempas): a Novel Agent For the Treatment of Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension

doi:

Figure Lengend Snippet: Adverse Events Reported in at Least 5% of Riociguat-Treated Patients And at a Frequency Greater Than Placebo in Phase 3 Clinical Trials 24 , 25

Article Snippet: 3 In October 2013, the Food and Drug Administration approved riociguat (Adempas, Bayer Healthcare Pharmaceuticals), the first agent in a novel therapeutic class called soluble guanylate cyclase (sGC) stimulators.

Techniques: Clinical Proteomics, Reflux, Infection