Review
Biochemistry & Molecular Biology
Jorge Rico-Fontalvo, Gustavo Aroca-Martinez, Rodrigo Daza-Arnedo, Jose Cabrales, Tomas Rodriguez-Yanez, Maria Cardona-Blanco, Juan Montejo-Hernandez, Dairo Rodelo Barrios, Jhonny Patino-Patino, Elber Osorio Rodriguez
Summary: Diabetic kidney disease (DKD) is a common complication of diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD) worldwide. Its development involves hemodynamic, metabolic, and inflammatory factors. Persistent albuminuria along with a decline in glomerular filtration rate (GFR) defines this disease, but novel biomarkers originating from its pathogenesis need to be discussed to aid in diagnosis, follow-up, treatment response, and prognosis.
Review
Endocrinology & Metabolism
Qinrui Wu, Fengjuan Huang
Summary: Diabetic kidney disease (DKD) is one of the most severe complications of diabetes mellitus (DM), and currently, the use of drugs for DKD treatment is limited. Recent research has shown that long non-coding RNA (lncRNA) H19 plays a critical role in the development of DKD, contributing to inflammation, apoptosis, ferroptosis, pyroptosis, autophagy, and oxidative damage.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Physiology
Mette Ostergaard, Thomas Secher, Michael Christensen, Casper Gravesen Salinas, Urmas Roostalu, Jacob Lercke Skytte, Ida Rune, Henrik H. Hansen, Jacob Jelsing, Niels Vrang, Lisbeth N. Fink
Summary: Translational animal models of diabetic kidney disease (DKD) are crucial for preclinical research and drug discovery. In a mouse model of hypertension-accelerated progressive DKD, standard care medications for controlling hypertension (lisinopril) and hyperglycemia (empagliflozin) have shown improvements in physiological and histopathological kidney disease markers. The study supports hypertension and type 2 diabetes as key drivers of DKD progression and offers a proof of concept for testing novel drugs in this model for potential nephroprotective effects.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Immunology
Swastika Sur, Mark Nguyen, Patrick Boada, Tara K. Sigdel, Hans Sollinger, Minnie M. Sarwal
Summary: The study analyzed transcriptional and protein data from different patient samples to investigate the pathophysiology of diabetic kidney disease (DKD) progression. By leveraging public and private human transcriptional datasets, innate immunity and inflammation were identified as key mechanistic pathways in DKD, with FcER1 being uncovered as a potential new target for rational drug design.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Naila Rabbani, Antonysunil Adaikalakoteswari, James R. R. Larkin, Sianna Panagiotopoulos, Richard J. J. MacIsaac, Dennis K. K. Yue, Gregory R. R. Fulcher, Matthew A. A. Roberts, Merlin A. Thomas, Elif Ekinci, Paul J. J. Thornalley
Summary: Accumulation of advanced glycation endproducts (AGEs) is associated with decline in renal function, particularly in diabetic patients. This study evaluated levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2-4 chronic kidney disease (CKD), and identified a specific AGE, methylglyoxal-derived hydroimidazolone (MG-H1) free adduct, as the most responsive to CKD status and diabetes. The concentration of MG-H1 free adduct in serum was strongly related to CKD stage and increased in diabetes. This suggests that serum MG-H1 free adduct may serve as a potential AGE risk marker for diabetic and non-diabetic CKD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Aggeliki Tserga, Despoina Pouloudi, Jean Sebastien Saulnier-Blache, Rafael Stroggilos, Irene Theochari, Harikleia Gakiopoulou, Harald Mischak, Jerome Zoidakis, Joost Peter Schanstra, Antonia Vlahou, Manousos Makridakis
Summary: This study investigates the molecular biology of early diabetic kidney disease (DKD) development and progression through comprehensive proteomic analysis of diabetic mice and human biopsies. The study identifies significant differential expression of peroxisomal proteins in the early stages of DKD, regardless of disease severity, suggesting potential markers for diabetic kidney dysfunction.
Article
Cell Biology
Frederikke E. Sembach, Helene M. AEgidius, Lisbeth N. Fink, Thomas Secher, Annemarie Aarup, Jacob Jelsing, Niels Vrang, Bo Feldt-Rasmussen, Kristoffer T. G. Rigbolt, Jens C. Nielsen, Mette V. Ostergaard
Summary: The study used RNAseq to compare gene expression profiles in early and advanced diabetic kidney disease (DKD) mouse models, revealing that UNx-Renin mice had more pronounced gene components associated with immune system activation and extracellular matrix remodeling, supporting histological hallmarks of disease progression. Integration of RNAseq at different levels provided enhanced resolution of molecular pathways associated with DKD progression and may aid in identifying novel therapeutic targets.
DISEASE MODELS & MECHANISMS
(2021)
Article
Biochemistry & Molecular Biology
Louise S. Dalboge, Michael Christensen, Martin Ronn Madsen, Thomas Secher, Nicole Endlich, Vedran Drenic', Alba Manresa-Arraut, Henrik H. Hansen, Ida Rune, Lisbeth N. Fink, Mette Ostergaard
Summary: The study found that the long-acting GLP-1R agonist semaglutide, in combination with the ACE inhibitor lisinopril, improved disease markers in an advanced DKD model. Semaglutide reduced hyperglycemia, hypertension, and albuminuria, while also improving the severity of glomerulosclerosis and inflammation and fibrogenesis gene expression markers. Co-administration of lisinopril further improved hypertension and glomerulosclerosis.
Article
Immunology
Sunna Nabeela, Abhijit Date, Ashraf S. Ibrahim, Priya Uppuluri
Summary: Dermatophytosis is a common fungal infection and a significant public health problem worldwide. Recent changes in the epidemiological patterns of fungal infections, particularly drug-resistant dermatophyte infections, have been observed. Diabetic patients experience more severe and recurrent dermatophytosis. In order to study dermatophytosis and evaluate potential treatments, a mouse model of dermatophyte infections in diabetic mice was established. The model demonstrated that alexidine dihydrochloride (AXD) was highly effective in treating fungal lesions, comparable to the standard drug terbinafine.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Mengdi Wang, Yanyu Pang, Yifan Guo, Lei Tian, Yufei Liu, Cun Shen, Mengchao Liu, Yuan Meng, Zhen Cai, Yuefen Wang, Wenjing Zhao
Summary: Diabetic kidney disease (DKD) is a common complication of diabetes mellitus, but its pathogenesis is poorly understood. Metabolic reprogramming plays a critical role in the development of DKD, and understanding its role may lead to new therapeutic approaches.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Ming Zhong, Enyi Zhu, Na Li, Lian Gong, Hai Xu, Yong Zhong, Kai Gong, Shan Jiang, Xiaohua Wang, Lingyan Fei, Chun Tang, Yan Lei, Zhongli Wang, Zhihua Zheng
Summary: This study aimed to find key diagnostic markers and therapeutic targets for diabetic kidney disease (DKD) through bioinformatics analysis. Four potential diagnostic markers were identified and their reliability was confirmed through experiments. These results contribute to the understanding and treatment of DKD.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Urology & Nephrology
Yann Salemkour, Dilemin Yildiz, Lea Dionet, Daan C. 't Hart, Kim A. T. Verheijden, Ryuta Sato, Nassim Mahtal, Jean-Daniel Delbet, Emmanuel Letavernier, Marion Rabant, Alexandre Karras, Johan van der Vlag, Tom Nijenhuis, Pierre-Louis Tharaux, Olivia Lenoir
Summary: This study reveals a new mechanism linking TRPC6 and calpain activity to impaired podocyte autophagy, podocyte injury, and proteinuria in diabetic kidney disease. Targeting TRPC6 and/or calpain to restore podocyte autophagy may offer a promising therapeutic strategy for diabetic kidney disease.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Medicine, General & Internal
Qi Li, Delma Veron, Alda Tufro
Summary: The molecular pathogenesis of diabetic kidney disease progression is complex and involves the regulation of Myo9A expression and S-nitrosylation by nitric oxide availability. Dysregulation of SNO-Myo9A, SNO-RhoA, and SNO-actin may contribute to the pathogenesis of advanced diabetic kidney disease and could be targeted for therapeutic interventions.
FRONTIERS IN MEDICINE
(2021)
Review
Medicine, General & Internal
Agnieszka Piwkowska, Lukasz Zdrojewski, Zbigniew Heleniak, Alicja Debska-Slizien
Summary: This article summarizes the current clinical state-of-the-art in the diagnosis of DKD and a selection of potential novel markers based on up-to-date literature.
Article
Biochemistry & Molecular Biology
Stephanie A. Eid, Phillipe D. O'Brien, Katharina H. Kretzler, Dae-Gyu Jang, Faye E. Mendelson, John M. Hayes, Andrew Carter, Hongyu Zhang, Subramaniam Pennathur, Frank C. Brosius, Emily J. Koubek, Eva L. Feldman
Summary: Patients with type 2 diabetes often experience complications such as diabetic kidney disease and diabetic peripheral neuropathy, which lower their quality of life and increase mortality. This study examined the therapeutic efficacy of three dietary interventions in a type 2 diabetes mouse model. The interventions improved weight and glycemic status and alleviated diabetic kidney disease, but did not affect diabetic peripheral neuropathy.
Article
Multidisciplinary Sciences
Alex A. Gutsol, Paula Blanco, Taben M. Hale, Jean-Francois Thibodeau, Chet E. Holterman, Rania Nasrallah, Jose W. N. Correa, Sergey A. Afanasiev, Rhian M. Touyz, Chris R. J. Kennedy, Dylan Burger, Richard L. Hebert, Kevin D. Burns
Summary: Current research on hypertension often uses animal models, but these models do not fully replicate the glomerular injuries seen in humans. This study evaluated four hypertensive models and found that only the clipped kidneys in 2K1C rats showed similar glomerulopathy to humans. To make animal studies more relevant, the criteria and classifications established in human pathology should be used for analysis and improvement.
Article
Endocrinology & Metabolism
Jay C. Jha, Aozhi Dai, Jessica Garzarella, Amelia Charlton, Sofia Urner, Jakob A. Ostergaard, Jun Okabe, Chet E. Holterman, Alison Skene, David A. Power, Elif I. Ekinci, Melinda T. Coughlan, Harald H. H. W. Schmidt, Mark E. Cooper, Rhian M. Touyz, Chris R. Kennedy, Karin Jandeleit-Dahm
Summary: Excessive production of renal reactive oxygen species (ROS) plays a major role in diabetic kidney disease (DKD). This study demonstrates that NADPH oxidase 5 (NOX5) acts as a predominant pro-oxidant enzyme in DKD, independent of the previously characterized NOX4 pathway. The overexpression of NOX5 in DKD exacerbates kidney damage through enhanced ROS formation and modulation of key molecules involved in inflammation, fibrosis, and redox balance. Furthermore, the only available NOX inhibitor, GKT137831, is found to be ineffective in the presence of NOX5 expression in diabetes. These findings highlight the superior targeting potential of NOX5 as compared to other NOX isoforms like NOX4 in human DKD.
Review
Endocrinology & Metabolism
Tanvi Bathla, Akram Abolbaghaei, Agafe Bless Reyes, Dylan Burger
Summary: Studying extracellular vesicles (EVs) in the context of gestational diabetes mellitus (GDM) can serve as novel biomarkers for changes in both mother and fetus, providing insights for the development of screening tools and exploring the underlying mechanisms to improve the associated risks.
DIABETES & VASCULAR DISEASE RESEARCH
(2022)
Letter
Oncology
Chet E. Holterman, Robert L. Myette, Dylan Burger, Christopher RJ. Kennedy
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Neurosciences
Daniel N. N. El Kodsi, Jacqueline M. M. Tokarew, Rajib Sengupta, Nathalie A. A. Lengacher, Ajanta Chatterji, Angela P. P. Nguyen, Heather Boston, Qiubo Jiang, Carina Palmberg, Chantal Pileggi, Chet E. E. Holterman, Bojan Shutinoski, Juan Li, Travis K. Fehr, Matthew J. LaVoie, Rajiv R. R. Ratan, Gary S. S. Shaw, Masashi Takanashi, Nobutaka Hattori, Christopher R. R. Kennedy, Mary-Ellen Harper, Arne Holmgren, Julianna J. J. Tomlinson, Michael G. G. Schlossmacher
Summary: The expression of PRKN gene is associated with young-onset Parkinson's disease and plays a role in redox homeostasis. In a mouse model, the loss of PRKN gene combined with Sod2 haploinsufficiency led to increased oxidative stress and altered redox changes in the cytosol. Further research revealed that PRKN gene is involved in the recycling of glutathione, affecting the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in cells.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Cell & Tissue Engineering
An Duong, Gaganvir Parmar, Aidan M. Kirkham, Dylan Burger, David S. Allan
Summary: This scoping review identifies the increasing interest in cell-based therapy using extracellular vesicles (EVs) and highlights the need for standardized product characterization, quantifiable product quality attributes, and consistent outcome reporting in clinical trials to facilitate the clinical translation of EV-based treatment.
Article
Biochemistry & Molecular Biology
Akram Abolbaghaei, Maddison Turner, Jean-Francois Thibodeau, Chet E. E. Holterman, Christopher R. J. Kennedy, Dylan Burger
Summary: Hypertension and diabetes induce vascular injury through unknown processes. Changes in extracellular vesicle composition may provide new insights. This study analyzed the protein composition of circulating extracellular vesicles from hypertensive, diabetic, and healthy mice, identifying differentially expressed proteins and potential pathways involved in vascular injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Transplantation
Robert L. Myette, Fengxia Xiao, Pavel Geier, Janusz Feber, Dylan Burger, Christopher R. J. Kennedy
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Oncology
Meshach Asare-Werehene, Robert A. A. Hunter, Emma Gerber, Arkadiy Reunov, Isaiah Brine, Chia-Yu Chang, Chia-Ching Chang, Dar-Bin Shieh, Dylan Burger, Hanan Anis, Benjamin K. K. Tsang
Summary: Late diagnosis and chemoresistance are major challenges in the treatment of ovarian cancer. A new nanosensor platform has been developed to detect ovarian cancer at an early stage and predict chemoresistance. Mechanistically, chemoresistant ovarian cancer cells produce plasma gelsolin (pGSN), which induces the formation of small extracellular vesicles that export cisplatin and prevent apoptosis in chemoresistant cells.
Article
Biochemistry & Molecular Biology
Shuhiba Mohammad, Jayonta Bhattacharjee, Velislava Tzaneva, Kelly Ann Hutchinson, Madeeha Shaikh, Danilo Fernandes da Silva, Dylan Burger, Kristi. B. B. Adamo
Summary: Exercise induces the release of small extracellular vesicles (sEVs) that may play a role in tissue cross-talk during exercise. In this study, sEVs released after exercise in pregnant and non-pregnant individuals were evaluated for their impact on trophoblasts in vitro. The results showed that exercise-associated sEVs localized within the cytoplasm of trophoblast cells, but did not significantly affect cell proliferation, gene expression, or hormone release. Further investigation is needed to reveal the potential role of exercise-associated sEVs in communicating the effects of exercise to the maternal-fetal interface.
Article
Chemistry, Medicinal
Brent J. Tschirhart, Xiangru Lu, Janice Gomes, Arundhasa Chandrabalan, Gillian Bell, David A. Hess, Guangxin Xing, Hong Ling, Dylan Burger, Qingping Feng
Summary: Sepsis is a dysregulated immune response to infection and a leading cause of mortality. Recombinant human Annexin A5 (Anx5) treatment has been shown to inhibit pro-inflammatory cytokine production and improve survival in sepsis models. It blocks the inflammatory response induced by activated platelets and microvesicles in endothelial cells through phosphatidylserine binding.
Article
Multidisciplinary Sciences
Nicholas D. Calvert, Alexia Kirby, Mojmir Suchy, Peter Pallister, Aidan A. Torrens, Dylan Burger, Gerd Melkus, Nicola Schieda, Adam J. Shuhendler
Summary: Chronic kidney disease (CKD) and acute kidney injury (AKI) are ongoing global health burdens. Glomerular filtration rate (GFR) is the gold standard measure of kidney function, and the addition of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) can provide a global assessment of kidney health with spatial information. A glucose-modified verdazyl called glucoverdazyl can be used for DCE-MRI to evaluate kidney function and its clearance rates can serve as a reliable surrogate measure of GFR.
NATURE COMMUNICATIONS
(2023)
Article
Urology & Nephrology
Uta Erdbrugger, Ewout J. J. Hoorn, Thu H. H. Le, Charles J. J. Blijdorp, Dylan Burger
Summary: Extracellular vesicles (EVs) are emerging as important mediators and biomarkers in kidney health and disease. They can provide valuable information about the state of the cells in the kidney and their role in various kidney diseases. However, the heterogeneity of EVs poses challenges in their separation and characterization. More sensitive tools are being developed to overcome these challenges. The therapeutic potential of EVs in kidney diseases has been extensively studied in animal models and the field of EV diagnostics and therapeutics is advancing rapidly.
Article
Endocrinology & Metabolism
Julie Semenchuk, Katie Sullivan, Rahim Moineddin, Farid Mahmud, Allison Dart, Brandy Wicklow, Fengxia Xiao, Thalia Medeiros, James Scholey, Dylan Burger
Summary: The study found that interleukin-9 (IL-9) is associated with podocyte injury in early type 1 diabetes, and there are complex interactions between urinary IL-9, inflammatory cytokines, and ACR (urinary albumin/creatinine ratio, a measure of podocyte injury).
ACTA DIABETOLOGICA
(2022)
