Article
Critical Care Medicine
Thorben Pape, Temitayo Opemipo Idowu, Valerie Maritta Etzrodt, Klaus Stahl, Benjamin Seeliger, Hermann Haller, Sascha David
Summary: The antifungal drug Bifonazole can reduce the release and biosynthesis of endothelial-destabilizing factor Angpt-2 in vitro, improving vascular barrier function. Further studies are needed to investigate the underlying mechanism and translate these findings to in vivo models.
Review
Cell Biology
Katharina E. M. Hellenthal, Laura Brabenec, Nana-Maria Wagner
Summary: The loss of endothelial barrier function during systemic inflammation is a key contributor to organ dysfunction and mortality. Endothelial cells play a critical role in maintaining organ integrity and regulating tissue perfusion. Inflammatory stimuli can activate endothelial cells, leading to a loss of endothelial barrier function and the development of tissue edema and hypotension, which are lethal outcomes.
Article
Ophthalmology
Emmi Kapiainen, Harri Elamaa, Ilkka Miinalainen, Valerio Izzi, Lauri Eklund
Summary: This study demonstrates the additive effect of Angpt4 in maintaining SC and activating Tie2, as well as the synergistic interaction between Angpt4 and Angpt2. The interplay between the angiopoietins is crucial for maintaining the integrity of the iridocorneal angle.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Anna S. Pavlova, Kristina I. Yakovleva, Anna V. Epanchitseva, Maxim S. Kupryushkin, Inna A. Pyshnaya, Dmitrii V. Pyshnyi, Elena I. Ryabchikova, Ilya S. Dovydenko
Summary: The study showed that siRNA modified with the phosphoryl guanidine (PG) group exhibited increased resistance to RNase A but decreased thermodynamic stability. However, PG-modified siRNA retained its activity when the modifications were introduced into the passenger strand.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Hara Kang, Yun Ji Ga, Soo Hyun Kim, Young Hoon Cho, Jung Won Kim, Chaeyeon Kim, Jung-Yong Yeh
Summary: RNA has become a revolutionary tool in battling emerging infectious diseases, particularly in response to the COVID-19 pandemic. RNAi therapeutics have shown potential in reducing disease-associated genes, and nucleic acid-based therapies have emerged as alternative treatments. However, there are obstacles to overcome in the use of siRNA-based antiviral therapies, including off-target effects and drug resistance.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Medicine, General & Internal
Giuseppe Gargano, Antonio Oliviero, Francesco Oliva, Nicola Maffulli
Summary: SiRNA can participate in the process of tendon healing and identify potential therapeutic targets. However, there is controversy over the regulation of genes and growth factors involved in tendon diseases and healing processes by siRNAs.
BRITISH MEDICAL BULLETIN
(2021)
Article
Oncology
Ha -Ram Park, Anahita Shiva, Portia Cummings, Seoyeon Kim, Sungsoo Kim, Eunhyeong Lee, Alessandra Leong, Subrata Chowdhury, Carrie Shawber, Richard Carvajal, Gavin Thurston, Joon-Yong An, Amanda W. Lund, Hee Won Yang, Minah Kim
Summary: The position of T-cells in the tumor microenvironment affects their ability to encounter the tumor and kill it. The vascular destabilizing factor ANGPT2 causes vascular integrity issues in the tumor periphery, leading to a lack of T-cell infiltration in the tumor core, which is associated with a poor response to immunotherapy.
Review
Pharmacology & Pharmacy
Priyanga Ranasinghe, Melisande L. Addison, James W. Dear, David J. Webb
Summary: Post-transcriptional gene silencing can be achieved through siRNA therapy, which uses synthetic short double-stranded RNA molecules to specifically target and degrade mRNA transcripts. This technology offers advantages such as broad targeting capabilities and long-lasting effects. However, challenges in terms of pharmacokinetics and pharmacodynamics have been addressed through chemical modification and delivery systems. Several siRNA therapies have been approved for clinical use, but further advancements are needed to target organs beyond the liver and reach special sites.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Pan Liu, Michael Ryczko, Xinfang Xie, Jason Baardsnes, Simon Lord-Dufour, Yves Duroche, Emily Anne Hicks, Aftab Taiyab, Heather Sheardown, Susan E. Quaggin, Jing Jin
Summary: The study introduces a new soluble ANG1 mimetic, Hepta-ANG1, which effectively reduces vascular leakage by activating the Tie2 signaling pathway. This fusion protein displays remarkable stability and high multimericity, making it a potential candidate for treating inflammatory vascular leak disorders.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Review
Medicine, Research & Experimental
Santoshi Naik, Ajjappla Basavaraj Shreya, Ruchira Raychaudhuri, Abhijeet Pandey, Shaila A. Lewis, Manali Hazarika, Sulatha Bhandary, Bola Sadashiva Satish Rao, Srinivas Mutalik
Summary: This article discusses the current research on using siRNA-based gene silencing strategies to treat glaucoma, including discussions on ocular structures, administration routes, viral and non-viral vectors, as well as basic strategies and challenges in siRNA therapy. Different therapeutic targets for glaucoma, current siRNA-based drugs used in treatment, and strategies for siRNA-based treatment after glaucoma surgery are also briefly mentioned.
Article
Biochemistry & Molecular Biology
Julien Ouvrard, Lisa Muniz, Estelle Nicolas, Didier Trouche
Summary: siRNAs can induce transcriptional silencing of chromatin-associated noncoding RNA through base-pairing with the target sequence. Transcriptional silencing occurs only in cis, and both Ago1 and Ago2 are involved.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Review
Medicine, General & Internal
Giuseppe Gargano, Giovanni Asparago, Filippo Spiezia, Francesco Oliva, Nicola Maffulli
Summary: Small interfering RNAs (siRNAs) have potential therapeutic applications in osteoporosis and can be used to study metabolic processes and identify new drug targets. However, it is challenging to predict the in vivo response of siRNAs and drugs based on in vitro studies.
BRITISH MEDICAL BULLETIN
(2023)
Article
Engineering, Biomedical
Siming Huang, Hongbo Le, Guobin Hong, Guosheng Chen, Fang Zhang, Liejing Lu, Xiang Zhang, Ya Qiu, Zhe Wang, Qinyuan Zhang, Gangfeng Ouyang, Jun Shen
Summary: This study constructs a biomimetic nanohybrid platform with tumor targeting, monitoring, and treatment functions for cancer ferroptosis therapy. By inhibiting the synthesis of glutathione (GSH), it promotes the accumulation of reactive oxygen species (ROS) and inactivates glutathione peroxidase 4 (GPX4) to enhance iron-induced ferroptosis. The biomimetic nanohybrid shows remarkable anti-cancer effect and enables magnetic resonance imaging (MRI) monitoring of therapy.
ACTA BIOMATERIALIA
(2022)
Article
Immunology
Jianxiong Zeng, Zhifei Luo, Shupeng Dong, Xiaochun Xie, Xinyan Liang, Youzhen Yan, Qiming Liang, Zhen Zhao
Summary: The study identified a complex interaction network between ZIKV-derived viRNAs and their viral RNA targets, demonstrating that viRNA production from ZIKV mRNA depends on Dicer function and is a limiting factor for ZIKV virulence in NSCs.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Pediatrics
Umar Salimi, Heather L. Menden, Sherry M. Mabry, Sheng Xia, Venkatesh Sampath
Summary: In a study on sepsis-induced bronchopulmonary dysplasia (BPD), recombinant ANGPT1 was found to preserve endothelial quiescence, inhibit acute lung injury (ALI), and suppress alveolar simplification. This suggests that Angiopoietin 1-based interventions may be effective in mitigating sepsis-induced lung injury and BPD in premature infants.
PEDIATRIC RESEARCH
(2022)
Letter
Urology & Nephrology
Rebecca Thorsness, Nathan H. Raines, Elizabeth M. White, Christopher M. Santostefano, Samir M. Parikh, Melissa R. Riester, Richard A. Feifer, Vincent Mor, Andrew R. Zullo
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)
Article
Urology & Nephrology
Justin M. Belcher, Xavier Vela Parada, Douglas A. Simonetto, Luis A. Juncos, Nithin Karakala, Hani M. Wadei, Pratima Sharma, Kevin R. Regner, Mitra K. Nadim, Guadalupe Garcia-Tsao, Juan Carlos Q. Velez, Samir M. Parikh, Raymond T. Chung, Andrew S. Allegretti
Summary: Hepatorenal syndrome (HRS) is a severe form of acute kidney injury that occurs in patients with advanced cirrhosis. Terlipressin, a synthetic vasopressin analogue, is commonly used as a first-line therapy in many countries, but not approved in the United States. A recent randomized trial in North America raised concerns about the potential respiratory adverse events and lack of evidence for mortality benefit associated with terlipressin.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)
Article
Urology & Nephrology
Sherry G. Mansour, Pavan K. Bhatraju, Steven G. Coca, Wassim Obeid, Francis P. Wilson, Ian B. Stanaway, Yaqi Jia, Heather Thiessen-Philbrook, Alan S. Go, T. Alp Ikizler, Edward D. Siew, Vernon M. Chinchilli, Chi-yuan Hsu, Amit X. Garg, W. Brian Reeves, Kathleen D. Liu, Paul L. Kimmel, James S. Kaufman, Mark M. Wurfel, Jonathan Himmelfarb, Samir M. Parikh, Chirag R. Parikh, ASSESS-AKI Consortium
Summary: A higher Angpt-1:Angpt-2 ratio is strongly associated with reduced risk of CKD progression, heart failure, and mortality in patients with AKI.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Thomas R. Martin, Rachel L. Zemans, Lorraine B. Ware, Eric P. Schmidt, David W. H. Riches, Lisa Bastarache, Carolyn S. Calfee, Tushar J. Desai, Susanne Herold, Catherine L. Hough, Mark R. Looney, Michael A. Matthay, Nuala Meyer, Samir M. Parikh, Troy Stevens, B. Taylor Thompson
Summary: Clinical and molecular heterogeneity are common features of diseases, and understanding their basis can lead to significant advances in treatment. Although heterogeneity is common in ARDS in terms of risk factors, disease severity, and outcomes, challenges remain in understanding the clinical and molecular basis and using it to personalize therapy for patients.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Wensheng Qu, Kenneth M. Ralto, Tao Qin, Yinhong Cheng, Weifeng Zong, Xiang Luo, Miguel Perez-Pinzon, Samir M. Parikh, Cenk Ayata
Summary: NAD(+) precursor supplements have a neuroprotective effect when administered after ischemia onset, but continuous treatment for three days before ischemia exacerbates infarct enlargement and worsens neurological deficits. The difference may be due to the single dose of NAM or NR augmenting tissue AMPK, PGC1 alpha, SIRT1, and ATP, while the multiple-dose paradigm fails to do so.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Nathan H. Raines, Dominick A. Leone, Cristina O'Callaghan-Gordo, Oriana Ramirez-Rubio, Juan Jose Amador, Damaris Lopez Pilarte, Iris S. Delgado, Jessica H. Leibler, Nieves Embade, Ruben Gil-Redondo, Chiara Bruzzone, Maider Bizkarguenaga, Madeleine K. Scammell, Samir M. Parikh, Oscar Millet, Daniel R. Brooks, David J. Friedman
Summary: Mesoamerican nephropathy (MeN) is a chronic kidney disease that mainly affects young men in Mesoamerica, and its pathogenesis is poorly understood. A study comparing the urine metabolome of men engaged in strenuous agricultural labor in Nicaragua with different referent groups revealed distinguishing metabolic features in the high-risk group, including increased gut-derived metabolites and decreased metabolites related to central energy metabolism. Additionally, a higher kynurenate/tryptophan ratio was found in the high-risk group, suggesting an elevated inflammatory state.
Article
Critical Care Medicine
Ari Moskowitz, Katherine M. Berg, Anne V. Grossestreuer, Lakshman Balaji, Xiaowen Liu, Michael N. Cocchi, Maureen Chase, Michelle Ng Gong, Jonathan Gong, Samir M. Parikh, Long Ngo, Noa Berlin, Michael W. Donnino
Summary: Thiamine supplementation does not significantly attenuate kidney injury in patients with septic shock, but it does increase ICU-free days.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Urology & Nephrology
Masaomi Nangaku, A. Richard Kitching, Peter Boor, Alessia Fornoni, Jurgen Floege, P. Toby Coates, Jonathan Himmelfarb, Rachel Lennon, Hans-Joachim Anders, Benjamin D. Humphreys, Fergus J. Caskey, Agnes B. Fogo
Summary: The International Society of Nephrology organized the TRANSFORM meeting to provide guidance on translational animal studies for new drug development in kidney disease. The meeting covered various themes such as disease model selection, pharmacokinetics, interventions, choice of animal, statistical power, organoids and organ-on-a-chip models, and reporting of results. These recommendations aim to accelerate the development of new drugs for efficacious diseases.
KIDNEY INTERNATIONAL
(2023)
Editorial Material
Urology & Nephrology
Marie Christelle Saade, Samir M. Parikh
Article
Medicine, Research & Experimental
Alec A. Schmaier, Papa F. Anderson, Siyu M. Chen, Emale El-Darzi, Ivan Aivasovsky, Milan P. Kaushik, Kelsey D. Sack, H. Criss Hartzell, Samir M. Parikh, Robert Flaumenhaft, Sol Schulman
Summary: The study found that endothelial cells can switch from an anticoagulant surface to a procoagulant surface under pathogenic stimuli, promoting thrombotic cardiovascular disease. Two TMEM16 family members, TMEM16F and TMEM16E, were identified as crucial for the procoagulant activity of endothelial cells. In addition, the TMEM16 inhibitor benzbromarone was found to prevent endothelial cell procoagulant activity and thrombus formation.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Urology & Nephrology
Amanda J. Clark, Marie Christelle Saade, Samir M. Parikh
Summary: Acute kidney injury (AKI) is a serious and prevalent disease, and the alterations in renal NAD+ biosynthesis are characteristic of AKI. Targeting NAD+ as a therapy for AKI shows potential, but further understanding of the underlying mechanisms is needed. This article summarizes the NAD+ biosynthesis alterations in the kidney during AKI and explores the implications in other conditions such as inflammation, pregnancy, and cancer.
SEMINARS IN NEPHROLOGY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Alec A. Schmaier, Papa Freduah F. Anderson, Siyu F. Chen, Samir M. Parikh, Robert C. Flaumenhaft, Sol Schulman
Article
Medicine, Research & Experimental
Kensei Taguchi, Bertha C. Elias, Sho Sugahara, Snehal Sant, Benjamin S. Freedman, Sushrut S. Waikar, Ambra Pozzi, Roy Zent, Raymond C. Harris, Samir M. Parikh, Craig R. Brooks
Summary: Acute kidney injury (AKI) can lead to chronic kidney disease (CKD) through maladaptive repair of proximal tubule cells (PTCs), involving dedifferentiation and profibrotic cytokine secretion. Cyclin G1 (CG1) and cyclin-dependent kinase 5 (CDK5) are key factors in maladaptive dedifferentiation and could be therapeutic targets for CKD.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Endocrinology & Metabolism
Dominik Saul, Jad Sfeir, Annupam Kotwal, Samir Parikh, Tait Shanafelt, Elizabeth Atkinson, Sara Achenbach, Matthew Drake
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Urology & Nephrology
Mary Baliker, Nisha Bansal, Ian De Boer, Joseph Bonventre, Matthew Breyer, Arlene Chapman, Deidra Crews, Erich Ditschman, Silvia Ferre, Jennifer Flythe, Kevin Fowler, Nora Franceschini, Barry Freedman, Robert Friedman, Peter C. Harris, John Cijiang He, Jonathan Himmelfarb, Benjamin D. Humphreys, Orlando M. Gutierrez, Shuta Ishibe, Joe Ix, Nichole Jefferson, Bryan Kestenbaum, Jay Koyner, Holly Kramer, Precious McCowan, Ryan Murray, Opeyemi Olabisi, Paul Palevsky, Samir M. Parikh, Sharon Pearce, Janos Peti-Peterdi, Susan E. Quaggin, Janine Reed, Glenda V. Roberts, Anne Rohall-Andrade, Sylvia Rosas, Mark Sarnak, Julie J. Scialla, Steve Seliger, Eddie Siew, John David Spencer, Katalin Susztak, Joseph Vassalotti, Kerry Willis, Bessie A. Young, Troy Zimmerman
Summary: Despite the high prevalence and economic burden of chronic kidney disease (CKD) in the United States, federal funding for kidney-related research, prevention, and education activities is inadequate compared to other chronic diseases. More federal support is needed to promote critical research that will expand knowledge of kidney health and disease, develop new and effective therapies, and reduce health disparities. The National Kidney Foundation (NKF) held Research Roundtables to identify priorities for preclinical and clinical kidney-related research. These priorities, presented in a position statement, offer attainable opportunities for groundbreaking innovations that will benefit patients with kidney disease in the next 5-10 years.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)