Article
Chemistry, Medicinal
Shinya Fujii, Eriko Kikuchi, Honoka Suzuyama, Yuko Watanabe, Mari Ishigami-Yuasa, Hiroyuki Masuno, Takayasu Mori, Kiyoshi Isobe, Shinichi Uchida, Hiroyuki Kagechika
Summary: Hypertension is a crucial target for drug discovery, with a focus on the WNK-OSR1/SPAK-NCC signaling cascade. Through a screening system, the study investigated the structure-activity relationship of salicylanilide derivatives as SPAK kinase inhibitors. Compound 10 a was identified as a potent SPAK inhibitor with reduced toxicity, showing promising potential for a new class of antihypertensive drugs.
Review
Biochemistry & Molecular Biology
Sunday Solomon Josiah, Nur Farah Meor Azlan, Jinwei Zhang
Summary: This review summarizes the current understanding of the role of cation-chloride cotransporters in stroke, focusing on NKCC1, KCC3, and the WNK-SPAK/OSR1 signaling pathway. Inhibition of NKCC1 and activation of KCC3 can reduce intracellular chloride levels to exert neuroprotection, suggesting a potential novel therapeutic strategy for stroke.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
Shinichi Uchida, Takayasu Mori, Koichiro Susa, Eisei Sohara
Summary: In this study, the WNK kinases were identified as the causal genes for pseudohypoaldosteronism type II (PHAII). The researchers found that constitutive activation and increased phosphorylation of the NaCl cotransporter (NCC) play a primary role in the pathogenesis of PHAII. They also discovered the WNK-OSR1/SPAK-NCC signaling cascade, mediated by oxidative stress-response protein 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK), which regulates NCC and plays a crucial physiological role.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Archie Brown, Nur Farah Meor Azlan, Zhijuan Wu, Jinwei Zhang
Summary: Hypertension is a common health issue globally, with Gordon's syndrome being a form of secondary hypertension that may result from mutations in key genes. Treatment for Gordon's syndrome mainly involves the use of thiazide diuretics, but they come with side effects, leading to research efforts focusing on developing novel inhibitory molecules.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Urology & Nephrology
Soren B. Poulsen, Lei Cheng, David Penton, Marleen L. A. Kortenoeven, Vladimir V. Matchkov, Johannes Loffing, Robert Little, Sathish K. Murali, Robert A. Fenton
Summary: The beta 2-adrenergic receptor agonist salbutamol can increase NCC activity, affecting sodium and potassium homeostasis and potentially posing a risk factor for hypertension.
KIDNEY INTERNATIONAL
(2021)
Review
Physiology
Jacky Lo, Anna-Lena Forst, Richard Warth, Anselm A. Zdebik
Summary: This review provides an overview of the complex disease mechanisms and variable expression of disease symptoms associated with Kir4.1 and Kir5.1. Understanding the pathophysiology of these diseases and their multifaceted clinical spectrum is an important prerequisite for making the correct diagnosis and personalized therapies.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Physiology
Qin Guo, Ya Zhang, Geng-Ru Jiang, Chong Zhang
Summary: Familial hyperkalemic hypertension is a hereditary hypertensive disease caused by mutations in genes such as WNK1, WNK4, KLHL3, and CUL3. Decreased KLHL3 expression may contribute to abnormal renal sodium reabsorption under certain conditions.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Nur Farah Meor Azlan, Maarten P. Koeners, Jinwei Zhang
Summary: Hypertension, the leading cause of cardiovascular disease mortality worldwide, has been linked to alterations in the NCC and its regulatory mechanisms. Recent research has revealed significant progress in understanding the control of NCC, potentially identifying novel therapeutic targets for hypertension.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Pharmacology & Pharmacy
Hye Jin Yang, Mi Jung Kim, Sung Soo Kim, Young-Wuk Cho
Summary: The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons, where melatonin may promote wakefulness through modulating signaling pathways.
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
(2021)
Review
Cell Biology
Natalie A. Hager, Ceara K. McAtee, Mitchell A. Lesko, Allyson F. O'Donnell
Summary: Potassium (K+) homeostasis is crucial for cell and organismal health, and Kir family member Kir2.1 plays a significant role in maintaining potassium ion balance. Kir2.1 has specific functions in heart, muscle, and bone development, and its mutations are associated with diseases such as cardiomyopathies and neurological disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhihui Deng, Jianxin Zhen, Genelle F. Harrison, Guobin Zhang, Rui Chen, Ge Sun, Qiong Yu, Neda Nemat-Gorgani, Lisbeth A. Guethlein, Liumei He, Mingzhong Tang, Xiaojiang Gao, Siqi Cai, William H. Palmer, Jonathan A. Shortt, Christopher R. Gignoux, Mary Carrington, Hongyan Zou, Peter Parham, Wenxu Hong, Paul J. Norman
Summary: The Chinese Southern Han population exhibits a significant enrichment for interactions between inhibitory KIR and HLA-A and -B, which has been influenced by population admixture with neighboring populations. Over 80% of Southern Han HLA haplotypes encode more than one KIR ligand, enhancing NK cell repertoires in quantity, diversity, and effector strength, potentially increasing resistance to endemic viral infections.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Instruments & Instrumentation
Gihan Kamel, Stephane Lefrancois, Thierry Moreno, Mohammad Al-Najdawi, Yazeed Momani, Anas Abbadi, Giorgio Paolucci, Paul Dumas
Summary: SESAME is the only synchrotron light facility in the Middle East and neighboring regions, providing infrared spectromicroscopy services for the scientific community in the Middle East. The facility has a collaboration agreement with the French synchrotron facility SOLEIL, and the currently operational infrared beamline has been designed and implemented to meet the demands of various scientific communities in the Middle East.
JOURNAL OF SYNCHROTRON RADIATION
(2021)
Article
Food Science & Technology
Naveed Rasheed, Aftab Ahmed, Farhana Nosheen, Ali Imran, Fakhar Islam, Rabia Noreen, Anamika Chauhan, Mohd Asif Shah, Yuosra Amer Ali
Summary: The formation and release of eggs during ovulation are affected by high amounts of androgens. Seed cycling has been proven to be effective in the treatment of polycystic ovary syndrome (PCOS). Through dietary regulation and seed cycling, FSH and LH levels can be significantly reduced, improving hormonal imbalances in women with PCOS.
FOOD SCIENCE & NUTRITION
(2023)
Article
Critical Care Medicine
Wang Deng, Di Qi, Xu-Mao Tang, Xin-Yu Deng, Jing He, Dao-Xin Wang
Summary: The study demonstrated that the WNK4/SPAK signaling pathway improved alveolar fluid clearance in LPS-induced ARDS by upregulating ENaC and reducing pulmonary edema, resulting in enhanced survival rate.
Article
Immunology
Abeer N. Alshukairi, Jincun Zhao, Maha A. Al-Mozaini, Yanqun Wang, Ashraf Dada, Salim A. Baharoon, Sara Alfaraj, Waleed A. Ahmed, Mushira A. Enani, Fatehi E. Elzein, Nazik Eltayeb, Laila Layqah, Aiman El-Saed, Husam A. Bahaudden, Abdul Haseeb, Sherif A. El-Kafrawy, Ahmed M. Hassan, Najlaa A. Siddiq, Ibtihaj Alsharif, Isamel Qushmaq, Esam Azhar, Stanley Perlman, Ziad A. Memish
Summary: The study of antibody responses in MERS-CoV infection survivors in Saudi Arabia showed the presence of specific neutralizing antibodies up to 6 years postinfection. This finding provides crucial information for the development of MERS-CoV vaccines.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Clinical Neurology
Annegret Quade, Anne Thiel, Ingo Kurth, Manuel Holtgrewe, Miriam Elbracht, Dieter Beule, Katja Eggermann, Ute Scholl, Martin Haeusler
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2020)
Article
Endocrinology & Metabolism
Eric Seidel, Gudrun Walenda, Clemens Messerschmidt, Benedikt Obermayer, Mirko Peitzsch, Paal Wallace, Rohini Bahethi, Taekyeong Yoo, Murim Choi, Petra Schrade, Sebastian Bachmann, Gerhard Liebisch, Graeme Eisenhofer, Dieter Beule, Ute Scholl
ENDOCRINE CONNECTIONS
(2020)
Article
Medicine, General & Internal
U. I. Scholl
Summary: Aldosterone is produced in the adrenal cortex to regulate volume and electrolyte homeostasis. There are two types of hyperaldosteronism: primary and secondary. Primary aldosteronism, the most common cause of secondary hypertension, is associated with increased cardiovascular risk.
Review
Urology & Nephrology
Holger Scholz, Felix J. Boivin, Kai M. Schmidt-Ott, Sebastian Bachmann, Kai-Uwe Eckardt, Ute I. Scholl, Pontus B. Persson
Summary: The authors discuss the specific kidney regions that are at particular risk of injury, and how this information can help in finding new ways to mitigate injury and avoid permanent damage. They suggest that the physiological heterogeneity of the kidney should be considered when exploring novel renoprotective strategies, such as improving kidney tissue oxygenation and modulating cellular energy metabolism.
NATURE REVIEWS NEPHROLOGY
(2021)
Article
Multidisciplinary Sciences
Eric Seidel, Julia Schewe, Junhui Zhang, Hoang An Dinh, Sofia K. Forslund, Lajos Marko, Nicole Hellmig, Joerg Peters, Dominik N. Muller, Richard P. Lifton, Timothy Nottoli, Gabriel Stoelting, Ute Scholl
Summary: Gain-of-function mutations in the CACNA1H gene lead to familial hyperaldosteronism and early-onset hypertension, while knockout of the gene can be compensated for by activating alternative calcium entry pathways for aldosterone production.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Peripheral Vascular Disease
Ute Scholl
Summary: Primary aldosteronism is the most common cause of secondary hypertension, largely due to genetic mutations in ion channels and pumps. Somatic mutations are responsible for sporadic cases, while germline mutations cause familial hyperaldosteronism.
Article
Biochemistry & Molecular Biology
Paul-Emmanuel Vanderriele, Qing Wang, Anne-Marie Merillat, Frederique Ino, Gilles Aeschlimann, Xavier Ehret, David Ancin Del Olmo, Veronica Ponce de Leon, Ute I. Scholl, Denise V. Winter, Alex Odermatt, Edith Hummler, Sophia N. Verouti
Summary: Research on GR haploinsufficient Sprague Dawley rats revealed that they developed salt-sensitive hypertension on a high salt diet due to disruptions in sEH and fatty acid metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medical Laboratory Technology
Georgiana Constantinescu, Manuel Schulze, Mirko Peitzsch, Thomas Hofmockel, Ute Scholl, Tracy Ann Williams, Jacques W. M. Lenders, Graeme Eisenhofer
Summary: Combining mass spectrometry-based steroidomics with machine learning and laboratory information management systems can improve the accuracy and efficiency of endocrine diagnostics.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2022)
Article
Peripheral Vascular Disease
Yujiro Maeoka, Xiao-Tong Su, Wen-Hui Wang, Xin-Peng Duan, Avika Sharma, Na Li, Olivier Staub, James A. McCormick, David H. Ellison
Summary: The study suggests that MR is activated in the absence of aldosterone in DCT2 and partially CCD, indicating that glucocorticoid binding to MR may preserve sodium homeostasis in DCT2.
Article
Biotechnology & Applied Microbiology
Shiwei Zhou, Laura Johanna Lenk, Yawei Gao, Yuhui Wang, Xiaoe Zhao, Menghao Pan, Shuhong Huang, Kexin Sun, Peter Kalds, Qi Luo, Simon Lillico, Tad Sonstegard, Ute I. I. Scholl, Baohua Ma, Bjoern Petersen, Yulin Chen, Xiaolong Wang
Summary: This study demonstrates the potential of the prime editing (PE) system to edit the genomes of large animals for desired mutations and disease modeling. However, the editing frequencies are still unsatisfactory, highlighting the need for optimizations in the PE system for efficient generation of large animals with customized traits.
Article
Physiology
Ryan J. Cornelius, Jonathan W. Nelson, Xiao-Tong Su, Chao-Ling Yang, David H. Ellison
Summary: Cullin-RING ligases are a type of E3 ubiquitin ligases that control cellular processes by regulating degradation. Genetic deletion of renal-specific genes results in a reduction of NCC due to hypoplasia of the DCT, which coincides with cortical kidney injury.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Article
Urology & Nephrology
Annika Etges, Nicole Hellmig, Gudrun Walenda, Bassam G. Haddad, Jan-Philipp Machtens, Thomas Morosan, Lars Christian Rump, Ute I. Scholl
Summary: This study reported a patient with pseudohypoaldosteronism type II (PHA II) who presented with hypertension, hyperkalemic acidosis, and severe muscle pain associated with chronic kidney disease (CKD). Genetic analysis revealed a homozygous mutation in the KLHL3 gene, which was found to increase WNK4 protein levels and sodium chloride reabsorption, leading to PHA II.
Review
Endocrinology & Metabolism
Martin Reincke, Irina Bancos, Paolo Mulatero, Ute Scholl, Michael Stowasser, Tracy Ann Williams
Summary: Primary aldosteronism is a common cause of secondary hypertension, often underestimated. Clinicians need to conduct a multistep diagnostic investigation to choose appropriate treatment. Timely detection and targeted treatment can improve patient quality of life and reduce complications.
LANCET DIABETES & ENDOCRINOLOGY
(2021)
Article
Biology
Matthias Haase, Anne Thiel, Ute I. Scholl, Hany Ashmawy, Matthias Schott, Margret Ehlers
BMC RESEARCH NOTES
(2020)
Article
Physiology
Xiao-Tong Su, Nathan J. Klett, Avika Sharma, Charles N. Allen, Wen-Hui Wang, Chao-Ling Yang, David H. Ellison
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2020)