A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension
Genetic variants in the third intron of the PRDM6 gene have been associated with BP traits in multiple GWAS. By combining fine mapping, massively parallel reporter assays, and gene editing, we identified super enhancers that drive the expression of PRDM6 and are partly regulated by STAT1 as the causal variants for hypertension. The heterozygous disruption of Prdm6 in mice expressing Cre recombinase under the control of mouse smooth muscle cell protein 22-α promoter (Prdm6fl/+ SM22-Cre) exhibited a markedly higher number of renin-producing cells in the kidneys at E18.5 compared with WT littermates and developed salt-induce...
Source: Journal of Clinical Investigation - February 15, 2023 Category: Biomedical Science Authors: Kushan L. Gunawardhana, Lingjuan Hong, Trojan Rugira, Severin Uebbing, Joanna Kucharczak, Sameet Mehta, Dineth R. Karunamuni, Brenda Cabera-Mendoza, Neeru Gandotra, Curt Scharfe, Renato Polimanti, James P. Noonan, Arya Mani Source Type: research
Renin –angiotensin–aldosterone pathway modulators in chronic kidney disease: A comparative review
Chronic kidney disease presents a health challenge that has a complex underlying pathophysiology, both acquired and inherited. The pharmacotherapeutic treatment options available today lower the progression of the disease and improve the quality of life but cannot completely cure it. This poses a challenge to the healthcare provider to choose, from the available options, the best way to manage the disease as per the presentation of the patient. As of now, the recommended first line of treatment to control the blood pressure in chronic kidney disease is the administration of renin–angiotensin–aldosterone system modulato...
Source: Frontiers in Pharmacology - February 13, 2023 Category: Drugs & Pharmacology Source Type: research
Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study
CONCLUSION: Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.PMID:36630006 | DOI:10.1007/s40620-022-01530-7 (Source: Journal of Nephrology)
Source: Journal of Nephrology - January 11, 2023 Category: Urology & Nephrology Authors: Davina N W Lie Kam Wa Chan Alexander H N Tang Anthony T P Chan Gary C W Chan Kar Neng Lai Sydney Chi-Wai Tang Source Type: research
Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study
CONCLUSION: Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.PMID:36630006 | DOI:10.1007/s40620-022-01530-7 (Source: Journal of Nephrology)
Source: Journal of Nephrology - January 11, 2023 Category: Urology & Nephrology Authors: Davina N W Lie Kam Wa Chan Alexander H N Tang Anthony T P Chan Gary C W Chan Kar Neng Lai Sydney Chi-Wai Tang Source Type: research
Mathematical modeling of antihypertensive therapy
This study is a continuation of research on the modular agent-based model of the cardiovascular and renal systems (presented in the previously published article). In the current work, we included in the model equations simulating the response to antihypertensive therapies with different mechanisms of action. For this, we used the pharmacodynamic effects of the angiotensin II receptor blocker losartan, the calcium channel blocker amlodipine, the angiotensin-converting enzyme inhibitor enalapril, the direct renin inhibitor aliskiren, the thiazide diuretic hydrochlorothiazide, and the β-blocker bisoprolol. We fitted therapy ...
Source: Frontiers in Physiology - December 14, 2022 Category: Physiology Source Type: research
Insight into the hepatoprotective, hypolipidemic, and antidiabetic impacts of aliskiren in streptozotocin-induced diabetic liver disease in mice
Diabetic hepatopathy is a serious complication of poorly controlled diabetes mellitus. An efficient antidiabetic drug which keeps normal liver tissues is not available. The renin-angiotensin system has been re... (Source: Diabetology and Metabolic Syndrome)
Source: Diabetology and Metabolic Syndrome - October 31, 2022 Category: Endocrinology Authors: Amal M. Mahfoz and Aya Y. Gawish Tags: Research Source Type: research
Correction: The role of aliskiren in the management of hypertension and major cardiovascular outcomes: a systematic review and meta-analysis
Journal of Human Hypertension, Published online: 29 July 2022; doi:10.1038/s41371-022-00739-0Correction: The role of aliskiren in the management of hypertension and major cardiovascular outcomes: a systematic review and meta-analysis (Source: Journal of Human Hypertension)
Source: Journal of Human Hypertension - July 29, 2022 Category: Cardiology Authors: Henrik Laurits Bjerre Julie B. Christensen Niels Henrik Buus Ulf Simonsen Junjing Su Source Type: research
Molecules, Vol. 27, Pages 4828: Aliskiren Hemifumarate Proliposomes for Improved Oral Drug Delivery: Formulation Development, In Vitro and In Vivo Permeability Testing
The objective of this study was to develop proliposomal formulations for a poorly bioavailable drug, aliskiren hemifumarate (AKH). A solvent evaporation method was used to prepare proliposomes using different lipids. The lipids of selection were soy phosphatidylcholine (SPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoylphosphatidylglycerol sodium (DMPG Na), stearylamine, and cholesterol in various ratios. Proliposomes were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics upon hydration with aqueous phase. In vitro drug release studies were con...
Source: Molecules - July 28, 2022 Category: Chemistry Authors: Priyanka Kunamaneni Surya Kovvasu Steven Yeung Jeffrey Wang Salim Shah Guru Betageri Tags: Article Source Type: research
Molormer: a lightweight self-attention-based method focused on spatial structure of molecular graph for drug-drug interactions prediction
Brief Bioinform. 2022 Jul 19:bbac296. doi: 10.1093/bib/bbac296. Online ahead of print.ABSTRACTMulti-drug combinations for the treatment of complex diseases are gradually becoming an important treatment, and this type of treatment can take advantage of the synergistic effects among drugs. However, drug-drug interactions (DDIs) are not just all beneficial. Accurate and rapid identifications of the DDIs are essential to enhance the effectiveness of combination therapy and avoid unintended side effects. Traditional DDIs prediction methods use only drug sequence information or drug graph information, which ignores information a...
Source: Briefings in Bioinformatics - July 18, 2022 Category: Bioinformatics Authors: Xudong Zhang Gan Wang Xiangyu Meng Shuang Wang Ying Zhang Alfonso Rodriguez-Paton Jianmin Wang Xun Wang Source Type: research
Molormer: a lightweight self-attention-based method focused on spatial structure of molecular graph for drug-drug interactions prediction
Brief Bioinform. 2022 Jul 19:bbac296. doi: 10.1093/bib/bbac296. Online ahead of print.ABSTRACTMulti-drug combinations for the treatment of complex diseases are gradually becoming an important treatment, and this type of treatment can take advantage of the synergistic effects among drugs. However, drug-drug interactions (DDIs) are not just all beneficial. Accurate and rapid identifications of the DDIs are essential to enhance the effectiveness of combination therapy and avoid unintended side effects. Traditional DDIs prediction methods use only drug sequence information or drug graph information, which ignores information a...
Source: Briefings in Bioinformatics - July 18, 2022 Category: Bioinformatics Authors: Xudong Zhang Gan Wang Xiangyu Meng Shuang Wang Ying Zhang Alfonso Rodriguez-Paton Jianmin Wang Xun Wang Source Type: research
Molormer: a lightweight self-attention-based method focused on spatial structure of molecular graph for drug-drug interactions prediction
Brief Bioinform. 2022 Jul 19:bbac296. doi: 10.1093/bib/bbac296. Online ahead of print.ABSTRACTMulti-drug combinations for the treatment of complex diseases are gradually becoming an important treatment, and this type of treatment can take advantage of the synergistic effects among drugs. However, drug-drug interactions (DDIs) are not just all beneficial. Accurate and rapid identifications of the DDIs are essential to enhance the effectiveness of combination therapy and avoid unintended side effects. Traditional DDIs prediction methods use only drug sequence information or drug graph information, which ignores information a...
Source: Briefings in Bioinformatics - July 18, 2022 Category: Bioinformatics Authors: Xudong Zhang Gan Wang Xiangyu Meng Shuang Wang Ying Zhang Alfonso Rodriguez-Paton Jianmin Wang Xun Wang Source Type: research
Novel therapeutic modalities target cell signaling of Renin-Angiotensin system/NF-κB-induced cell cycle arrest and apoptosis in urethane-induced lung cancer in mice: An in vivo study
CONCLUSION: RAS/NF-B cell signaling is a potential therapeutic target for preventing and treating lung adenocarcinoma, evidenced by the fundamental cytotoxic mechanism and attenuation of metastasis and angiogenesis induced by the treatment of NSCLC mice with aliskiren.PMID:35822566 | DOI:10.1002/jbt.23162 (Source: Cancer Control)
Source: Cancer Control - July 13, 2022 Category: Cancer & Oncology Authors: Marwa M Khalaf Amira M Abo-Youssef Marina N Malak Mohamed A Hamzawy Source Type: research
The Prevalence of Adverse Drug Reactions and Adverse Drug Events from Heart Failure Medications in Frail Older Adults: A Systematic Review
ConclusionThe potential harms from heart failure medications in frail older people are poorly studied and understood. Clinical trials and pharmacovigilance studies should include frailty as a covariate to inform medication optimisation for this vulnerable and growing population.RegistrationProspero registration number: CRD 42021253762.Graphical Abstract (Source: Drugs and Aging)
Source: Drugs and Aging - June 28, 2022 Category: Geriatrics Source Type: research
The influence of prorenin/(pro)renin receptor on progesterone secretion by the bovine corpus luteum
Anim Reprod Sci. 2022 Apr 29;241:106985. doi: 10.1016/j.anireprosci.2022.106985. Online ahead of print.ABSTRACTThe aim of this study was to evaluate the role of prorenin/(pro)renin receptor activation on luteal progesterone (P4) secretion. Our hypothesis was that the nonproteolytic activation of (pro)renin receptor [P(RR)] is part of the regulatory mechanism responsible for corpus luteum (CL) function. In the first three experiments, prorenin was found to stimulate the production of P4, which is not inhibited by an angiotensin receptor antagonist (saralasin), but rather by a renin/prorenin inhibitor (aliskiren), a MAPK1/3 ...
Source: Animal Reproduction Science - May 15, 2022 Category: Zoology Authors: Andressa Minussi Pereira Dau Paulo Roberto da Rosa Joabel Dos Santos Juliana Ferst Mariana de Macedo Monique Rovani Fabio Comim Alfredo Quites Antoniazzi Bernardo Gasperin Rog ério Ferreira Paulo Bayard Gon çalves Source Type: research
The influence of prorenin/(pro)renin receptor on progesterone secretion by the bovine corpus luteum
Anim Reprod Sci. 2022 Apr 29;241:106985. doi: 10.1016/j.anireprosci.2022.106985. Online ahead of print.ABSTRACTThe aim of this study was to evaluate the role of prorenin/(pro)renin receptor activation on luteal progesterone (P4) secretion. Our hypothesis was that the nonproteolytic activation of (pro)renin receptor [P(RR)] is part of the regulatory mechanism responsible for corpus luteum (CL) function. In the first three experiments, prorenin was found to stimulate the production of P4, which is not inhibited by an angiotensin receptor antagonist (saralasin), but rather by a renin/prorenin inhibitor (aliskiren), a MAPK1/3 ...
Source: Animal Reproduction Science - May 15, 2022 Category: Zoology Authors: Andressa Minussi Pereira Dau Paulo Roberto da Rosa Joabel Dos Santos Juliana Ferst Mariana de Macedo Monique Rovani Fabio Comim Alfredo Quites Antoniazzi Bernardo Gasperin Rog ério Ferreira Paulo Bayard Gon çalves Source Type: research
