Fructosyl Amino Oxidase as a Therapeutic Enzyme in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.

Application of Machine Learning in Chronic Kidney Disease: Current Status and Future Prospects.

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.

Factors to take into account when interpreting 25-hydroxy-vitamin D serum levels.

BACKGROUND: Assessing vitamin D status, typically evaluated using serum or plasma 25-hydroxy vitamin D [25(OH)D] concentration, is complex because of various influencing factors. METHODS: Seasonality significantly affects intra-individual variability in 25(OH)D levels. This variation can be addressed by employing cosinor functions that are tailored to the geographical location of the patient to correct for seasonal effects. In addition to seasonality, genetic factors, such as DBP polymorphism and body composition, particularly adiposity, play crucial roles. Dialysis patients with DBP 2-2 phenotype exhibit higher vitamin D requirements. Genotyping/phenotyping of DBP allows for better tailored vitamin D supplementation. The lipid-soluble nature of vitamin D also interacts with plasma components such as serum triglycerides, which can influence vitamin D measurements. Adiposity, which is negatively correlated with vitamin D concentration, necessitates body mass-based mathematical adjustments for accurate vitamin D assessment in subjects with extreme BMI values. CONCLUSIONS: Accordingly, vitamin D replacement therapy must be personalized, taking into account factors such as body size and seasonal variations, to effectively reach the target serum 25(OH)D concentrations.

The potential role of vitamin D binding protein in kidney disease: a comprehensive review.

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.

A meta-analysis of the placebo response in vitiligo: Causes and consequences for the interpretation of clinical trials.

The current understanding of the placebo response in vitiligo is limited. Nonetheless, it is difficult to compare the outcomes of vitiligo trials if the repigmentation rates in placebo patients vary significantly. We conducted a meta-analysis of the placebo response in vitiligo trials. Overall, repigmentation rates in patients receiving placebo were 22%, ranging substantially from 0 to 60%. Repigmentation (>25%) was still relatively common for placebo (9.35%), but fell to 5% when >50% improvement was analyzed. Higher frequencies of placebo responses correlated with more repigmentation in the intervention groups. Facial vitiligo and sunlight exposure was linked to higher placebo responses. Roughly estimating the amount of improvement using quartiles (0-25, 25%-50%, 50%-75%, 75%-100% repigmentation) resulted in higher placebo rates compared to other assessment methods. In clinical studies with older patients, the ratio of placebo reactions to treatment responses was higher. This is likely because clinical trials with older patients reported less repigmentation after treatment than studies with younger patients. The percentual difference in affected body surface area during the study period ranged from 6.2% worsening to 17.6% improvement in the placebo groups. This high variability in placebo responses illustrates the need for standardized outcome measures and more head-to-head trials in vitiligo.

Infrared Spectroscopy: A New Frontier in Hematological Disease Diagnosis.

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.

From Vibrations to Visions: Raman Spectroscopy's Impact on Skin Cancer Diagnostics.

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.

The Impact of Antioxidants on Vitiligo and Melasma: A Scoping Review and Meta-Analysis.

Reactive oxygen species (ROS) generated during melanogenesis make melanocytes particularly vulnerable to oxidative stress, influencing their survival and melanin synthesis. Oxidative stress, significantly present in vitiligo and recently also detected in melasma, triggers inflammatory cascades and melanogenesis, making antioxidants a promising therapeutic avenue. A systematic search was conducted on Embase and Pubmed to study the efficacy of antioxidants for treating vitiligo and/or melasma. Meta-analysis was performed to assess the difference in Melasma Severity Index (MASI) scores between baseline and follow-up. Various antioxidants like polypodium leucotomos, ginkgo biloba, catalase/superoxide dismutase, and vitamin E have potential in vitiligo. For melasma, vitamin C, silymarin, and niacinamide were among those showing promise in reducing pigmentation, with vitamin C displaying significant effects in meta-analysis. Different antioxidants improve both vitiligo and melasma, with an increased minimal erythema dose (MED) following UV exposure being significant for vitiligo and tyrosinase inhibition being crucial for melasma. However, the efficacy of individual antioxidants varies, and their exact mechanisms, especially in stimulating melanocyte proliferation and anti-inflammatory pathways, require further investigation to understand better and optimize their use.

The role of sRAGE in cardiovascular diseases.

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.

Unlocking the link between haptoglobin polymorphism and noninfectious human diseases: insights and implications.

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.

Unveiling the Hidden Power of Uromodulin: A Promising Potential Biomarker for Kidney Diseases.

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.

Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications.

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

Growth differentiation factor 15 (GDF-15) in kidney diseases.

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.

Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0.

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 [...].

Unlocking the Diagnostic Potential of Saliva: A Comprehensive Review of Infrared Spectroscopy and Its Applications in Salivary Analysis.

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.

Enzymatic Deglycation of Damaged Skin by Means of Combined Treatment of Fructosamine-3-Kinase and Fructosyl-Amino Acid Oxidase.

The consensus in aging is that inflammation, cellular senescence, free radicals, and epigenetics are contributing factors. Skin glycation through advanced glycation end products (AGEs) has a crucial role in aging. Additionally, it has been suggested that their presence in scars leads to elasticity loss. This manuscript reports fructosamine-3-kinase (FN3K) and fructosyl-amino acid oxidase (FAOD) in counteracting skin glycation by AGEs. Skin specimens were obtained (n = 19) and incubated with glycolaldehyde (GA) for AGE induction. FN3K and FAOD were used as monotherapy or combination therapy. Negative and positive controls were treated with phosphate-buffered saline and aminoguanidine, respectively. Autofluorescence (AF) was used to measure deglycation. An excised hypertrophic scar tissue (HTS) (n = 1) was treated. Changes in chemical bonds and elasticity were evaluated using mid-infrared spectroscopy (MIR) and skin elongation, respectively. Specimens treated with FN3K and FAOD in monotherapy achieved an average decrease of 31% and 33% in AF values, respectively. When treatments were combined, a decrease of 43% was achieved. The positive control decreased by 28%, whilst the negative control showed no difference. Elongation testing of HTS showed a significant elasticity improvement after FN3K treatment. ATR-IR spectra demonstrated differences in chemical bounds pre- versus post-treatment. FN3K and FAOD can achieve deglycation and the effects are most optimal when combined in one treatment.

The Potential Use of Near- and Mid-Infrared Spectroscopy in Kidney Diseases.

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).

Topical Application of Deglycating Enzymes as an Alternative Non-Invasive Treatment for Presbyopia.

Presbyopia is an age-related vision disorder that is a global public health problem. Up to 85% of people aged ≥40 years develop presbyopia. In 2015, 1.8 billion people globally had presbyopia. Of those with significant near vision disabilities due to uncorrected presbyopia, 94% live in developing countries. Presbyopia is undercorrected in many countries, with reading glasses available for only 6-45% of patients living in developing countries. The high prevalence of uncorrected presbyopia in these parts of the world is due to the lack of adequate diagnosis and affordable treatment. The formation of advanced glycation end products (AGEs) is a non-enzymatic process known as the Maillard reaction. The accumulation of AGEs in the lens contributes to lens aging (leading to presbyopia and cataract formation). Non-enzymatic lens protein glycation induces the gradual accumulation of AGEs in aging lenses. AGE-reducing compounds may be effective at preventing and treating AGE-related processes. Fructosyl-amino acid oxidase (FAOD) is active on both fructosyl lysine and fructosyl valine. As the crosslinks encountered in presbyopia are mainly non-disulfide bridges, and based on the positive results of deglycating enzymes in cataracts (another disease caused by glycation of lens proteins), we studied the ex vivo effects of topical FAOD treatment on the power of human lenses as a new potential non-invasive treatment for presbyopia. This study demonstrated that topical FAOD treatment resulted in an increase in lens power, which is approximately equivalent to the correction obtained by most reading glasses. The best results were obtained for the newer lenses. Simultaneously, a decrease in lens opacity was observed, which improved lens quality. We also demonstrated that topical FAOD treatment results in a breakdown of AGEs, as evidenced by gel permeation chromatography and a marked reduction in autofluorescence. This study demonstrated the therapeutic potential of topical FAOD treatment in presbyopia.

Pressure therapy for scars: Myth or reality? A systematic review.

BACKGROUND: Hypertrophic scarring is a deviate occurrence after wound closure and is a common burn sequela. The mainstay of scar treatment consists of a trifold approach: hydration, UV-protection and the use of pressure garments with or without extra paddings or inlays to provide additional pressure. Pressure therapy has been reported to induce a state of hypoxia and to reduce the expression pattern of transforming growth factor-ß1 (TGF-ß1), therefore limiting the activity of fibroblasts. However, pressure therapy is said to be largely based on empirical evidence and a lot of controversy concerning the effectiveness still prevails. Many variables influencing its effectivity, such as adherence to treatment, wear time, wash frequency, number of available pressure garment sets and amount of pressure remain only partially understood. This systematic review aims to give a complete and comprehensive overview of the currently available clinical evidence of pressure therapy. METHODS: A systematic search for articles concerning the use of pressure therapy in the treatment and prevention of scars was performed in 3 different databases (Pubmed, Embase, and Cochrane library) according to the PRISMA statement. Only case series, case-control studies, cohort studies, and RCTs were included. The qualitative assessment was done by 2 separate reviewers with the appropriate quality assessment tools. RESULTS: The search yielded 1458 articles. After deduplication and removal of ineligible records, 1280 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 17 articles were included. Comparisons between pressure or no pressure, low vs high pressure, short vs long duration and early vs late start of treatment were investigated. CONCLUSION: There is sufficient evidence that indicates the value of prophylactic and curative use of pressure therapy for scar management. The evidence suggests that pressure therapy is capable of improving scar color, thickness, pain, and scar quality in general. Evidence also recommends commencing pressure therapy prior to 2 months after injury, and using a minimal pressure of 20-25 mmHg. To be effective, treatment duration should be at least 12 months and even preferably up to 18-24 months. These findings were in line with the best evidence statement by Sharp et al. (2016).