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1.
Vitam Horm ; 125: 311-365, 2024.
Article in English | MEDLINE | ID: mdl-38997169

ABSTRACT

Advanced glycation end products (AGEs) are compounds formed via non-enzymatic reactions between reducing sugars and amino acids or proteins. AGEs can accumulate in various tissues and organs and have been implicated in the development and progression of various diseases, including lung diseases. The receptor of advanced glycation end products (RAGE) is a receptor that can bind to advanced AGEs and induce several cellular processes such as inflammation and oxidative stress. Several studies have shown that both AGEs and RAGE play a role in the pathogenesis of lung diseases, such as chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, cystic fibrosis, and acute lung injury. Moreover, the soluble form of the receptor for advanced glycation end products (sRAGE) has demonstrated its ability to function as a decoy receptor, possessing beneficial characteristics such as anti-inflammatory, antioxidant, and anti-fibrotic properties. These qualities make it an encouraging focus for therapeutic intervention in managing pulmonary disorders. This review highlights the current understanding of the roles of AGEs and (s)RAGE in pulmonary diseases and their potential as biomarkers and therapeutic targets for preventing and treating these pathologies.


Subject(s)
Glycation End Products, Advanced , Lung Diseases , Receptor for Advanced Glycation End Products , Humans , Glycation End Products, Advanced/metabolism , Receptor for Advanced Glycation End Products/metabolism , Lung Diseases/metabolism , Animals , Oxidative Stress/physiology
2.
Diagnostics (Basel) ; 14(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39001241

ABSTRACT

Acute kidney damage (AKI) is a serious and common consequence among critically unwell individuals. Traditional biomarkers, such as serum creatinine, frequently fail to detect AKI in its early stages, necessitating the development of new accurate early biomarkers. Tissue inhibitor of metalloproteinases 2 (TIMP-2) has emerged as a promising biomarker for predicting early AKI. The present narrative review investigates the role of TIMP-2 in AKI prediction in a variety of clinical scenarios. In the NephroCheck® test, TIMP-2 exceeds established biomarkers for the early identification of AKI in terms of sensitivity and specificity when combined with insulin-like growth factor-binding protein 7 (IGFBP-7). Elevated levels of these biomarkers can provide a warning signal for AKI two to three days before clinical symptoms appear. TIMP-2 and IGFBP-7 have high predictive values, with an area under the curve (AUC) typically above 0.8, indicating good predictive capacity. For example, the [TIMP-2] × [IGFBP-7] product produced an AUC of 0.85 in surgical patients at high risk. In critically ill patients, a threshold of 0.3 (ng/mL)2/1000 demonstrated 92% sensitivity and 72% specificity. Elevated TIMP-2 levels have been correlated with higher mortality rates and the need for renal replacement therapy (RRT). In sepsis-associated AKI (SA-AKI), TIMP-2 levels combined with clinical prognostic models improved predictive accuracy (AUC: 0.822). Furthermore, elevated urine TIMP-2 levels were good predictors of AKI in pediatric patients after cardiac surgery, with AUC-ROC values of up to 0.848. Urine output and the presence of concomitant disorders may influence the prognostic accuracy of these biomarkers; therefore, more research is needed to fully understand their utility. The predictive value of TIMP-2 could be strengthened by combining it with other clinical parameters, reinforcing its role in the early detection and treatment of AKI.

3.
Int J Mol Sci ; 25(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38892061

ABSTRACT

Renal amyloidosis is a set of complex disorders characterized by the deposition of amyloid proteins in the kidneys, which causes gradual organ damage and potential kidney failure. Recent developments in diagnostic methods, particularly mass spectrometry and proteome profiling, have greatly improved the accuracy of amyloid typing, which is critical for disease management. These technologies provide extensive insights into the specific proteins involved, allowing for more targeted treatment approaches and better patient results. Despite these advances, problems remain, owing to the heterogeneous composition of amyloid proteins and the varying efficacy of treatments based on amyloid type. Access to sophisticated diagnostics and therapy varies greatly, highlighting the global difference in renal amyloidosis management. Future research is needed to investigate next-generation sequencing and gene-editing technologies, like clustered regularly interspaced short palindromic repeats (CRISPR), which promise more profound insights into the genetic basis of amyloidosis.


Subject(s)
Amyloidosis , Kidney Diseases , Humans , Amyloidosis/diagnosis , Amyloidosis/therapy , Amyloidosis/genetics , Amyloidosis/metabolism , Kidney Diseases/diagnosis , Kidney Diseases/therapy , Kidney Diseases/genetics , Proteomics/methods , Mass Spectrometry/methods
4.
Int J Mol Sci ; 25(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892184

ABSTRACT

The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive technology used to transform the landscape of cancer diagnosis in gynecology. By collecting the distinctive vibrational frequencies of chemical bonds inside tissue samples, Fourier-transform infrared (FTIR) spectroscopy provides a 'molecular fingerprint' that outperforms existing diagnostic approaches. We highlight significant advances in this field, particularly the identification of discrete biomarker bands in the mid- and near-IR spectra. Proteins, lipids, carbohydrates, and nucleic acids exhibited different absorption patterns. These spectral signatures not only serve to distinguish between malignant and benign diseases, but also provide additional information regarding the cellular changes associated with cancer. To underscore the practical consequences of these findings, we examined studies in which IR spectroscopy demonstrated exceptional diagnostic accuracy. This review supports the use of IR spectroscopy in normal clinical practice, emphasizing its capacity to detect and comprehend the intricate molecular underpinnings of gynecological cancers.


Subject(s)
Genital Neoplasms, Female , Humans , Female , Genital Neoplasms, Female/diagnosis , Spectroscopy, Fourier Transform Infrared/methods , Biomarkers, Tumor/analysis , Spectrophotometry, Infrared/methods , Early Detection of Cancer/methods
5.
Int J Mol Sci ; 25(11)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38892458

ABSTRACT

Vitamin D-binding protein (DBP), also known as Gc-globulin, is a protein that affects several physiological processes, including the transport and regulation of vitamin D metabolites. Genetic polymorphisms in the DBP gene have a significant impact on vitamin D levels and may have implications for disease risk. DBP polymorphisms are linked to differential immune responses, which could influence the onset of juvenile diseases. This narrative review examines the various roles of DBP, with a focus on bone health, immunological regulation, and lipid metabolism in children. Chronic disorders affected by DBP polymorphisms include bone abnormalities, autoimmune diseases, cardiovascular issues, childhood asthma, allergies, cystic fibrosis, acute liver failure, celiac disease, inflammatory bowel disease, and chronic kidney disease. Future research should focus on identifying the processes that underpin the many roles that DBP plays and developing customized therapeutics to improve health outcomes in the juvenile population.


Subject(s)
Vitamin D-Binding Protein , Humans , Vitamin D-Binding Protein/genetics , Vitamin D-Binding Protein/metabolism , Child , Child Health , Vitamin D/metabolism , Lipid Metabolism , Polymorphism, Genetic
6.
Biomedicines ; 12(3)2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38540181

ABSTRACT

The emergence of artificial intelligence and machine learning (ML) has revolutionized the landscape of clinical medicine, offering opportunities to improve medical practice and research. This narrative review explores the current status and prospects of applying ML to chronic kidney disease (CKD). ML, at the intersection of statistics and computer science, enables computers to derive insights from extensive datasets, thereby presenting an interesting landscape for constructing statistical models and improving data interpretation. The integration of ML into clinical algorithms aims to increase efficiency and promote its adoption as a standard approach to data interpretation in nephrology. As the field of ML continues to evolve, collaboration between clinicians and data scientists is essential for defining data-sharing and usage policies, ultimately contributing to the advancement of precision diagnostics and personalized medicine in the context of CKD.

7.
Acta Clin Belg ; 79(2): 130-142, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38166537

ABSTRACT

Chronic kidney disease (CKD) is a growing health concern with a complex etiological landscape. Among the numerous factors implicated, vitamin D binding protein (VDBP) has emerged as a focal point of scientific studies because of its critical role in vitamin D metabolism and immune modulation. The relationship between VDBP and CKD reveals a complex web of molecular and biochemical details that have great potential for improving diagnostic understanding and treatment strategies for CKD. This review summarizes the multifaceted roles of VDBP, including its molecular dynamics, interactions with vitamin D, and subsequent implications for kidney function. The main focus of the discussion is how VDBP affects bone mineral homeostasis, highlighted by the dysregulation of calcium and phosphorus metabolism, which is a part of the pathophysiology of CKD. The discussion also touches on the immunomodulatory scope of VDBP and how it may reduce the chronic inflammatory environment that accompanies CKD. The diagnostic potential of VDBP as a biomarker for CKD has been rigorously examined, highlighting its capacity to improve early detection and prognostic assessment. Modification of VDBP activity has the potential to slow the course of CKD and improve patient outcomes. Furthermore, a detailed examination of the genetic polymorphisms of VDBP and their implications for CKD susceptibility and treatment responsiveness provides a perspective for personalized medical methods. Prospects for the future depend on the expansion of studies that try to understand the molecular mechanisms underlying the VDBP-CKD interaction, in addition to clinical trials that evaluate the effectiveness of VDBP-focused treatment approaches.


Subject(s)
Renal Insufficiency, Chronic , Vitamin D-Binding Protein , Vitamin D , Humans , Vitamin D-Binding Protein/metabolism , Vitamin D-Binding Protein/genetics , Renal Insufficiency, Chronic/metabolism , Vitamin D/metabolism , Vitamin D/therapeutic use , Biomarkers/metabolism
8.
J Clin Med ; 12(23)2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38068480

ABSTRACT

Raman spectroscopy, a non-invasive diagnostic technique capturing molecular vibrations, offers significant advancements in skin cancer diagnostics. This review delineates the ascent of Raman spectroscopy from classical methodologies to the forefront of modern technology, emphasizing its precision in differentiating between malignant and benign skin tissues. Our study offers a detailed examination of distinct Raman spectroscopic signatures found in skin cancer, concentrating specifically on squamous cell carcinoma, basal cell carcinoma, and melanoma, across both in vitro and in vivo research. The discussion extends to future possibilities, spotlighting enhancements in portable Raman instruments, the adoption of machine learning for spectral data refinement, and the merging of Raman imaging with other diagnostic techniques. The review culminates by contemplating the broader implications of these advancements, suggesting a trajectory that may significantly optimize the accuracy and efficiency of skin cancer diagnostics.

9.
Int J Mol Sci ; 24(23)2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38069330

ABSTRACT

Hematological diseases, due to their complex nature and diverse manifestations, pose significant diagnostic challenges in healthcare. The pressing need for early and accurate diagnosis has driven the exploration of novel diagnostic techniques. Infrared (IR) spectroscopy, renowned for its noninvasive, rapid, and cost-effective characteristics, has emerged as a promising adjunct in hematological diagnostics. This review delves into the transformative role of IR spectroscopy and highlights its applications in detecting and diagnosing various blood-related ailments. We discuss groundbreaking research findings and real-world applications while providing a balanced view of the potential and limitations of the technique. By integrating advanced technology with clinical needs, we offer insights into how IR spectroscopy may herald a new era of hematological disease diagnosis.


Subject(s)
Hematologic Diseases , Hematology , Humans , Spectroscopy, Fourier Transform Infrared/methods , Spectrophotometry, Infrared/methods , Hematologic Diseases/diagnosis
10.
Adv Clin Chem ; 117: 53-102, 2023.
Article in English | MEDLINE | ID: mdl-37973322

ABSTRACT

Advanced glycation end products (AGEs), by-products of glucose metabolism, have been linked to the emergence of cardiovascular disorders (CVD). AGEs can cause tissue damage in four different ways: (1) by altering protein function, (2) by crosslinking proteins, which makes tissue stiffer, (3) by causing the generation of free radicals, and (4) by activating an inflammatory response after binding particular AGE receptors, such as the receptor for advanced glycation end products (RAGE). It is suggested that the soluble form of RAGE (sRAGE) blocks ligand-mediated pro-inflammatory and oxidant activities by serving as a decoy. Therefore, several studies have investigated the possible anti-inflammatory and anti-oxidant characteristics of sRAGE, which may help lower the risk of CVD. According to the results of various studies, the relationship between circulating sRAGE, cRAGE, and esRAGE and CVD is inconsistent. To establish the potential function of sRAGE as a therapeutic target in the treatment of cardiovascular illnesses, additional studies are required to better understand the relationship between sRAGE and CVD. In this review, we explored the potential function of sRAGE in different CVD, highlighting unanswered concerns and outlining the possibilities for further investigation.


Subject(s)
Cardiovascular Diseases , Humans , Cardiovascular Diseases/metabolism , Glycation End Products, Advanced/metabolism , Receptor for Advanced Glycation End Products/metabolism
11.
Crit Rev Clin Lab Sci ; : 1-23, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38013410

ABSTRACT

Haptoglobin (Hp) is a polymorphic protein that was initially described as a hemoglobin (Hb)-binding protein. The major functions of Hp are to scavenge Hb, prevent iron loss, and prevent heme-based oxidation. Hp regulates angiogenesis, nitric oxide homeostasis, immune responses, and prostaglandin synthesis. Genetic polymorphisms in the Hp gene give rise to different phenotypes, including Hp 1-1, Hp 2-1, and Hp 2-2. Extensive research has been conducted to investigate the association between Hp polymorphisms and several medical conditions including cardiovascular disease, inflammatory bowel disease, cancer, transplantation, and hemoglobinopathies. Generally, the Hp 2-2 phenotype is associated with increased disease risk and poor outcomes. Over the years, the Hp 2 allele has spread under genetic pressures. Individuals with the Hp 2-2 phenotype generally exhibit lower levels of CD163 expression in macrophages. The decreased expression of CD163 may be associated with the poor antioxidant capacity in the serum of subjects carrying the Hp 2-2 phenotype. However, the Hp 1-1 phenotype may confer protection in some cases. The Hp1 allele has strong antioxidant, anti-inflammatory, and immunomodulatory properties. It is important to note that the benefits of the Hp1 allele may vary depending on genetic and environmental factors as well as the specific disease or condition under consideration. Therefore, the Hp1 allele may not necessarily confer advantages in all situations, and its effects may be context-dependent. This review highlights the current understanding of the role of Hp polymorphisms in cardiovascular disease, inflammatory bowel disease, cancer, transplantation, hemoglobinopathies, and polyuria.

12.
J Pers Med ; 13(10)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37888058

ABSTRACT

Chronic Kidney Disease (CKD) constitutes a global health crisis, silently affecting millions worldwide [...].

13.
Diagnostics (Basel) ; 13(19)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37835820

ABSTRACT

Uromodulin, also known as Tamm-Horsfall protein, represents the predominant urinary protein in healthy individuals. Over the years, studies have revealed compelling associations between urinary and serum concentrations of uromodulin and various parameters, encompassing kidney function, graft survival, cardiovascular disease, glucose metabolism, and overall mortality. Consequently, there has been a growing interest in uromodulin as a novel and effective biomarker with potential applications in diverse clinical settings. Reduced urinary uromodulin levels have been linked to an elevated risk of acute kidney injury (AKI) following cardiac surgery. In the context of chronic kidney disease (CKD) of different etiologies, urinary uromodulin levels tend to decrease significantly and are strongly correlated with variations in estimated glomerular filtration rate. The presence of uromodulin in the serum, attributable to basolateral epithelial cell leakage in the thick ascending limb, has been observed. This serum uromodulin level is closely associated with kidney function and histological severity, suggesting its potential as a biomarker capable of reflecting disease severity across a spectrum of kidney disorders. The UMOD gene has emerged as a prominent locus linked to kidney function parameters and CKD risk within the general population. Extensive research in multiple disciplines has underscored the biological significance of the top UMOD gene variants, which have also been associated with hypertension and kidney stones, thus highlighting the diverse and significant impact of uromodulin on kidney-related conditions. UMOD gene mutations are implicated in uromodulin-associated kidney disease, while polymorphisms in the UMOD gene show a significant association with CKD. In conclusion, uromodulin holds great promise as an informative biomarker, providing valuable insights into kidney function and disease progression in various clinical scenarios. The identification of UMOD gene variants further strengthens its relevance as a potential target for better understanding kidney-related pathologies and devising novel therapeutic strategies. Future investigations into the roles of uromodulin and regulatory mechanisms are likely to yield even more profound implications for kidney disease diagnosis, risk assessment, and management.

14.
Adv Clin Chem ; 114: 1-46, 2023.
Article in English | MEDLINE | ID: mdl-37268330

ABSTRACT

Growth differentiation factor-15 (GDF-15) is a GDF subfamily member with potential kidney protective functions. Its nephroprotective activity is associated with both inflammation downregulation and upregulation of nephroprotective factors with anti-inflammatory activity, such as Klotho in tubular cells. However, GDF-15 has diverse and partially opposing functions depending on the state of the cells and the microenvironment. Increased GDF-15 levels have been linked to an increased risk of incident chronic kidney disease and a faster decline in kidney function in various renal disorders, including diabetic nephropathy, IgA nephropathy, lupus nephritis, anti-glomerular basement membrane nephritis, primary membranous nephropathy, kidney transplantation, Fabry disease and amyloidosis. The mechanisms underlying these effects are not yet fully understood. In this review, we will summarize GDF-15's potential role as a biomarker for kidney function in the general population, as well as in some specific kidney diseases.


Subject(s)
Kidney Diseases , Renal Insufficiency, Chronic , Humans , Growth Differentiation Factor 15
15.
Int J Mol Sci ; 24(12)2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37373463

ABSTRACT

Vitamin D, often referred to as the "sunshine nutrient", has gained considerable attention in recent years due to its multifaceted impact on health and disease [...].


Subject(s)
Vitamin D Deficiency , Vitamin D , Humans , Vitamin D/metabolism , Vitamin D-Binding Protein , Sunlight , Vitamins
16.
J Pers Med ; 13(6)2023 May 28.
Article in English | MEDLINE | ID: mdl-37373896

ABSTRACT

Infrared (IR) spectroscopy is a noninvasive and rapid analytical technique that provides information on the chemical composition, structure, and conformation of biomolecules in saliva. This technique has been widely used to analyze salivary biomolecules, owing to its label-free advantages. Saliva contains a complex mixture of biomolecules including water, electrolytes, lipids, carbohydrates, proteins, and nucleic acids which are potential biomarkers for several diseases. IR spectroscopy has shown great promise for the diagnosis and monitoring of diseases such as dental caries, periodontitis, infectious diseases, cancer, diabetes mellitus, and chronic kidney disease, as well as for drug monitoring. Recent advancements in IR spectroscopy, such as Fourier-transform infrared (FTIR) spectroscopy and attenuated total reflectance (ATR) spectroscopy, have further enhanced its utility in salivary analysis. FTIR spectroscopy enables the collection of a complete IR spectrum of the sample, whereas ATR spectroscopy enables the analysis of samples in their native form, without the need for sample preparation. With the development of standardized protocols for sample collection and analysis and further advancements in IR spectroscopy, the potential for salivary diagnostics using IR spectroscopy is vast.

18.
Int J Mol Sci ; 24(7)2023 Apr 04.
Article in English | MEDLINE | ID: mdl-37047712

ABSTRACT

Traditional renal biomarkers such as serum creatinine and albuminuria/proteinuria are rather insensitive since they change later in the course of the disease. In order to determine the extent and type of kidney injury, as well as to administer the proper therapy and enhance patient management, new techniques for the detection of deterioration of the kidney function are urgently needed. Infrared spectroscopy is a label-free and non-destructive technique having the potential to be a vital tool for quick and inexpensive routine clinical diagnosis of kidney disorders. The aim of this review is to provide an overview of near- and mid-infrared spectroscopy applications in patients with acute kidney injury and chronic kidney disease (e.g., diabetic nephropathy and glomerulonephritis).


Subject(s)
Diabetic Nephropathies , Glomerulonephritis , Humans , Kidney/diagnostic imaging , Glomerulonephritis/diagnosis , Spectrophotometry, Infrared , Proteinuria
19.
Int J Mol Sci ; 24(5)2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36902073

ABSTRACT

Vitamin D is a fat-soluble secosteroid that exists in two forms: vitamin D2 and vitamin D3 [...].


Subject(s)
Vitamin D-Binding Protein , Vitamin D , Cholecalciferol/metabolism , Ergocalciferols/metabolism , Vitamin D/metabolism , Vitamin D-Binding Protein/metabolism
20.
Int J Mol Sci ; 24(3)2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36769213

ABSTRACT

Advanced glycation end products (AGEs) are a class of compounds formed by nonenzymatic interactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs can alter the protein structure and activate one of their receptors, specifically the receptor for advanced glycation end products (RAGE). These phenomena impair the functions of cells, extracellular matrix, and tissues. RAGE is expressed by a variety of cells and has been linked to chronic inflammatory autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. The soluble (s)RAGE cleavage product is a positively charged 48-kDa cleavage product that retains the ligand binding site but loses the transmembrane and signaling domains. By acting as a decoy, this soluble receptor inhibits the pro-inflammatory processes mediated by RAGE and its ligands. In the present review, we will give an overview of the role of AGEs, sRAGE, and RAGE polymorphisms in several rheumatic diseases. AGE overproduction may play a role in the pathogenesis and is linked to accelerated atherosclerosis. Low serum sRAGE concentrations are linked to an increased cardiovascular risk profile and a poor prognosis. Some RAGE polymorphisms may be associated with increased disease susceptibility. Finally, sRAGE levels can be used to track disease progression.


Subject(s)
Arthritis, Rheumatoid , Sjogren's Syndrome , Humans , Receptor for Advanced Glycation End Products/genetics , Receptor for Advanced Glycation End Products/metabolism , Chronic Disease , Glycation End Products, Advanced/metabolism
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