Article
Multidisciplinary Sciences
Jakob Appel Ostergaard, Fanny Jansson Sigfrids, Carol Forsblom, Emma H. Dahlstrom, Lena M. Thorn, Valma Harjutsalo, Allan Flyvbjerg, Steffen Thiel, Troels Krarup Hansen, Per-Henrik Groop
Summary: The study found that H-ficolin predicts diabetes-related mortality but has no association with all-cause mortality or cardiovascular events. Additionally, H-ficolin is related to the progression of DKD, but not independently in fully adjusted models.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Domenico Mercurio, Arianna Piotti, Alessia Valente, Marco Oggioni, Yolanda Ponstein, Edwin Van Amersfoort, Marco Gobbi, Stefano Fumagalli, Maria-Grazia De Simoni
Summary: The study demonstrates that rhC1INH shows stronger neuroprotective effects after experimental ischemia/reperfusion injury in the brain, reducing behavioral deficits and neuronal loss, decreasing MBL deposition in the brain, and reducing the formation of complement C4b active fragments. In contrast, pdC1INH, despite having a longer plasma residence time, does not exhibit these neuroprotective effects. Therefore, rhC1INH may be a promising drug for stroke as it effectively inhibits MBL.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Review
Immunology
Benjamin Y. F. So, Gary C. W. Chan, Desmond Y. H. Yap, Tak Mao Chan
Summary: Primary membranous nephropathy (MN) is a significant cause of nephrotic syndrome and chronic kidney disease (CKD) in adults. The complement system plays a crucial role in the pathogenesis of MN, and detection of complement activation products could serve as a promising tool for non-invasive disease monitoring and prognosis. However, further research is needed to address concerns regarding the risk of infection and high treatment costs associated with complement-directed therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
D. E. Afsin, A. Aksakal, A. F. Kilic, N. K. Baygutalp, B. Kerget
Summary: This study aimed to determine the serum levels of mannose-binding lectin (MBL) and its relationship with intensive care hospitalization. The results showed significant differences in MBL levels between different severity groups of COVID-19 patients. MBL may serve as a prognostic biomarker in COVID-19 patients.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yanhong Ma, Fanghao Cai, Xiaohan Huang, Huijing Wang, Binfeng Yu, Junni Wang, Wanyun Nie, Kedan Cai, Yi Yang, Jianghua Chen, Liang Xiao, Fei Han
Summary: Increased serum mannose-binding lectin (MBL) level has been proven to correlate with the development of diabetic nephropathy (DN). This study found that MBL promotes the progression of DN by activating the nuclear factor-kappa B pathway in macrophages. This finding provides a new direction for the treatment of DN patients.
Article
Chemistry, Multidisciplinary
S. Moein Moghimi, Hajira B. Haroon, Anan Yaghmur, Dmitri Simberg, Panagiotis N. Trohopoulos
Summary: The contribution of the complement system to host defence and homeostasis is well recognized. The mechanisms underlying complement activation by particulate systems are still not fully understood. Activation of the complement cascade can promote inflammatory reactions. Controlled antibody binding and sensing of particles by complement pattern-recognition molecules can trigger complement activation. Particle curvature and spacing arrangement of surface functional groups are important parameters modulating complement responses through engagement with antibodies and complement pattern-recognition molecules. Better understanding of these parameters could enable the engineering of drug carriers and biomedical platforms with tunable complement responses.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Immunology
Angelica Beate Winter Boldt, Camila de Freitas Oliveira-Tore, Gabriela Canalli Kretzschmar, Hellen Weinschutz Mendes, Servio Tulio Stinghen, Fabiana Antunes Andrade, Valeria Bumiller-Bini, Leticia Boslooper Goncalves, Anna Carolina de Moraes Braga, Ewalda von Rosen Seeling Stahlke, Thirumalaisamy P. Velavan, Steffen Thiel, Iara Jose Taborda de Messias-Reason
Summary: Polymorphisms of the complement system influence susceptibility to leprosy and HBV coinfection, with certain genetic combinations increasing infection risk while others provide protection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Panteleimon Charitos, Ingmar A. F. M. Heijnen, Adrian Egli, Stefano Bassetti, Marten Trendelenburg, Michael Osthoff
Summary: The study found that critically ill COVID-19 patients have an overactivated alternative pathway (AP) leading to complement consumption and reduced AP activity in vitro. The lectin pathway (LP) does not appear to play a role in the progression to severe COVID-19, while the significance of C1INH in COVID-19 requires further studies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Agriculture, Dairy & Animal Science
Peter A. Idowu, Adeola P. Idowu, Oliver T. Zishiri, Takalani J. Mpofu, Edwin J. A. Veldhuizen, Khathutshelo A. Nephawe, Bohani Mtileni
Summary: This article discusses the importance of mannose-binding lectin (MBL) in chickens and how it can aid in fighting bacterial pathogens. Studies show that MBL activates the complement system to help chickens resist pathogenic bacteria, and there is a direct link between MBL concentration and chicken health status.
Article
Cardiac & Cardiovascular Systems
Sara Meziani, Giulia Ferrannini, Mette Bjerre, Troels K. Hansen, Viveca Ritsinger, Anna Norhammar, Viveca Gyberg, Per Nasman, Lars Ryden, Linda G. Mellbin
Summary: This study aimed to investigate the differences in MBL levels between AMI patients and healthy controls, and the relationship between MBL and future cardiovascular events. The results showed that MBL levels were higher in patients during hospitalization compared to controls, but MBL was not independently associated with cardiovascular prognosis.
CARDIOVASCULAR DIABETOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Deeksha Marothia, Navdeep Kaur, Chetna Jhamat, Ipsa Sharma, Pratap Kumar Pati
Summary: Biotic and abiotic stresses have negative effects on plant's development and productivity. Researchers are studying the stress induced responses in plants and strategies to produce stress tolerant crops. Recent interest has focused on exploring the role of lectins in regulating biological responses in plants. Lectins are proteins that form reversible linkages with glycoconjugates. The involvement of plant lectins in stress tolerance is not fully understood and further research in this area could lead to improvements in crop production.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Multidisciplinary Sciences
Denise Chan, Phillip R. Bennett, Yun S. Lee, Samit Kundu, T. G. Teoh, Malko Adan, Saqa Ahmed, Richard G. Brown, Anna L. David, Holly Lewis, Belen Gimeno-Molina, Jane E. Norman, Sarah J. Stock, Vasso Terzidou, Pascale Kropf, Marina Botto, David A. MacIntyre, Lynne Sykes
Summary: This study provides mechanistic insight into the role of vaginal microbiota and immunological factors in spontaneous preterm birth (sPTB). The findings suggest that the complement system, in conjunction with specific vaginal microbial and associated immunological changes, contributes to the development of sPTB.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Claudia Grossi, Carolina Artusi, PierLuigi Meroni, Maria Orietta Borghi, Laura Neglia, Paola Adele Lonati, Marco Oggioni, Francesco Tedesco, Maria-Grazia De Simoni, Stefano Fumagalli
Summary: Beta-2 Glycoprotein I plays a role in brain injury following ischemic stroke by triggering hepatic production, enhancing vascular inflammation, interacting with mannose-binding lectin, and binding stressed neurons for clearance by phagocytosis.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Infectious Diseases
Marilia A. Sena, Priscila Mayrelle da Silva Castanha, Ana Beatriz Giles Guimaraes, Paula Alexandra dos Santos Oliveira, Maria Almerice Lopes da Silva, Marli Tenorio Cordeiro, Patricia Moura, Cynthia Braga, Luydson Richardson Silva Vasconcelos
Summary: The study found that variations in the MBL2 gene are associated with susceptibility to dengue infection in children. Lower levels of serum MBL are associated with dengue infection, while intermediate to high levels of serum MBL are associated with protection against dengue infection.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Agata Ciechanowska, Katarzyna Ciapala, Katarzyna Pawlik, Marco Oggioni, Domenico Mercurio, Maria-Grazia De Simoni, Joanna Mika
Summary: The study found that the brain responds strongly to traumatic brain injury by activating the local synthesis of classical and lectin complement pathway activators to counteract the damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Jussi Inkeri, Anniina Tynjala, Carol Forsblom, Ron Liebkind, Turgut Tatlisumak, Lena M. Thorn, Per-Henrik Groop, Sara Shams, Jukka Putaala, Juha Martola, Daniel Gordin
Summary: The study found that cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs) were present in individuals with type 1 diabetes. The presence of CMBs was associated with increased carotid intima-media thickness (CIMT), while individuals with WMHs had increased arterial stiffness and CIMT, but these associations were not independent of cardiovascular risk factors.
ACTA DIABETOLOGICA
(2021)
Article
Endocrinology & Metabolism
Jussi Inkeri, Krishna Adeshara, Valma Harjutsalo, Carol Forsblom, Ron Liebkind, Turgut Tatlisumak, Lena M. Thorn, Per-Henrik Groop, Sara Shams, Juha Martola, Jukka Putaala, Daniel Gordin
Summary: There was no association between glycemic control and cSVD in neurologically asymptomatic individuals with type 1 diabetes, prompting further studies to search for underlying factors of cSVD, despite the presence of a large number of signs of cerebrovascular pathology in these individuals after two decades of chronic hyperglycemia.
ACTA DIABETOLOGICA
(2022)
Article
Biochemistry & Molecular Biology
Sih Min Tan, Matthew Snelson, Jakob A. Ostergaard, Melinda T. Coughlan
Summary: The pathogenesis of diabetic kidney disease (DKD) involves disrupted energy generation in the kidney, leading to inflammation and fibrosis. Recent studies have shown the involvement of the innate immune complement system, particularly Complement C5a and C3a, in regulating metabolic responses in the diabetic kidney.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Medicine, Research & Experimental
Jakob A. Ostergaard, Jay C. Jha, Arpeeta Sharma, Aozhi Dai, Judy S. Y. Choi, Judy B. de Haan, Mark E. Cooper, Karin Jandeleit-Dahm
Summary: In a clinically relevant interventional model of established diabetic kidney disease (DKD), NLRP3 inhibition with MCC950 did not show renoprotective effects in diabetic mice. On the contrary, the use of MCC950 in diabetic mice led to increased renal inflammation, macrophage infiltration, oxidative stress, mesangial expansion, and glomerulosclerosis.
Article
Endocrinology & Metabolism
Stefan Mutter, Erkka Valo, Viljami Aittomaki, Kristian Nybo, Lassi Raivonen, Lena M. Thorn, Carol Forsblom, Niina Sandholm, Peter Wurtz, Per-Henrik Groop
Summary: This study found that branched-chain amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy, independent of baseline albuminuria and chronic kidney disease. Additionally, different associations were observed for overall progression, normoalbuminuria, and macroalbuminuria progression.
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.
Article
Endocrinology & Metabolism
Malene R. Jepsen, Jakob A. Ostergaard, Cheryl A. Conover, Lise Wogensen, Henrik Birn, Soren P. Krag, Robert A. Fenton, Claus Oxvig
Summary: This study found a significant increase in the activity of PAPP-A in diabetic kidneys, which correlated with glomerular filtration rate. Furthermore, it was discovered that STC1 and STC2 may balance IGF signaling in renal tissue by regulating PAPP-A activity, and imbalances in this system could potentially contribute to the development of DN.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Endocrinology & Metabolism
Anna Syreeni, Emma H. Dahlstrom, Stefanie Hagg-Holmberg, Carol Forsblom, Marika I. Eriksson, Valma Harjutsalo, Jukka Putaala, Per-Henrik Groop, Niina Sandholm, Lena M. Thorn
Summary: This study aimed to investigate the relationship between the haptoglobin Hp1/2 genotype and stroke in individuals with type 1 diabetes. The results showed that the haptoglobin genotypes had no association with the risk of stroke or survival after stroke in this cohort.
Editorial Material
Urology & Nephrology
Jakob A. Ostergaard, Mark E. Cooper
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Endocrinology & Metabolism
Patrik Smidtslund, Fanny Jansson Sigfrids, Anni Ylinen, Nina Elonen, Valma Harjutsalo, Per-Henrik Groop, Lena M. Thorn
Summary: This study aims to investigate the prognosis after a first-ever myocardial infarction (MI) in individuals with type 1 diabetes and how different MI- and diabetes-related factors affect the prognosis and risk of secondary cardiovascular events. The study found that individuals with type 1 diabetes have a high cardiovascular and diabetes-related mortality after their first-ever MI, and poor kidney function is associated with high mortality and excessive risk of secondary cardiovascular events.
Article
Immunology
G. H. Dorflinger, P. H. Hoyem, E. Laugesen, J. A. ostergaard, K. L. Funck, R. Steffensen, P. L. Poulsen, T. K. Hansen, M. Bjerre
Summary: Contrary to T1D, T2D is not per se associated with increased MBL serum level for a given MBL genotype or with diabetes duration. Serum MBL was inversely correlated with body fat percentage, and T2D patients with the high MBL expression genotype presented with deterioration of renal function.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Aleksi Tarkkonen, Tor-Bjorn Claesson, Marika I. Eriksson, Carol Forsblom, Lena M. Thorn, Paula Summanen, Per-Henrik Groop, Jukka Putaala, Daniel Gordin, Juha Martola
Summary: Using magnetic resonance imaging, we found that the optic tracts of individuals with type 1 diabetes were smaller than those of healthy controls, suggesting that chronic hyperglycemia also damages the optic tract. This damage was associated with various metabolic measures as well as diabetic complications such as eye disease, kidney disease, neuropathy, and cerebral microbleeds.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Om Prakash Dwivedi, Karina Barreiro, Annemari Karajamaki, Erkka Valo, Anil K. Giri, Rashmi B. Prasad, Rishi Das Roy, Lena M. Thorn, Antti Rannikko, Harry Holthoefer, Kim M. Gooding, Steven Sourbron, Denis Delic, Maria F. Gomez, Per-Henrik Groop, Tiinamaija Tuomi, Carol Forsblom, Leif Groop, Maija Puhka
Summary: By genome-wide sequencing of 200 urinary extracellular vesicle (uEV) mRNA samples from clinical studies, we identified potential candidate biomarkers and mechanisms for studying diabetic kidney disease (DKD) in Type 1 diabetes (T1D), which were validated in both Type 1 and 2 diabetes. The sequencing results revealed over 10,000 mRNAs with similarity to the kidney transcriptome. Thirteen upregulated genes predominantly expressed in proximal tubules, correlated with hyperglycemia and involved in cellular/oxidative stress homeostasis were found in T1D DKD groups. We constructed a transcriptional stress score based on six of these genes (GPX3, NOX4, MSRB, MSRA, HRSP12, and CRYAB), which reflected long-term decline of kidney function and could identify individuals with early decline even in normoalbuminuric patients.
Article
Ophthalmology
Thomas Stax Jakobsen, Jakob Appel ostergaard, Mads Kjolby, Elisa Lund Birch, Toke Bek, Anders Nykjaer, Thomas J. Corydon, Anne Louise Askou
Summary: The level and localization of the multifunctional receptor sortilin in the diabetic retina were investigated, and the effect of sortilin inhibition on retinal neurodegeneration in experimental diabetes was studied. Increased levels of sortilin were observed in human and murine diabetic retinas, and sortilin was highly localized to retinal Muller cells. Sortilin inhibition effectively protected against neuronal loss in diabetic mice by reducing inner retinal thickness and the count of retinal ganglion cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Endocrinology & Metabolism
M. I. Eriksson, A. Syreeni, N. Sandholm, E. H. Dahlstrom, D. Gordin, T. Tatlisumak, J. Putaala, Per-Henrik Groop, J. Martola, L. M. Thorn
Summary: This study aimed to evaluate the association between haptoglobin genotype and cerebral small-vessel disease (SVD). The results showed no significant association between haptoglobin genotype and SVD.
ACTA DIABETOLOGICA
(2023)