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1.
Vitam Horm ; 125: 311-365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38997169

RESUMO

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.


Assuntos
Produtos Finais de Glicação Avançada , Pneumopatias , Receptor para Produtos Finais de Glicação Avançada , Humanos , Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Pneumopatias/metabolismo , Animais , Estresse Oxidativo/fisiologia
2.
Diagnostics (Basel) ; 14(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39001241

RESUMO

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 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892184

RESUMO

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.


Assuntos
Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Biomarcadores Tumorais/análise , Espectrofotometria Infravermelho/métodos , Detecção Precoce de Câncer/métodos
4.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892458

RESUMO

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.


Assuntos
Proteína de Ligação a Vitamina D , Humanos , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo , Criança , Saúde da Criança , Vitamina D/metabolismo , Metabolismo dos Lipídeos , Polimorfismo Genético
5.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892061

RESUMO

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.


Assuntos
Amiloidose , Nefropatias , Humanos , Amiloidose/diagnóstico , Amiloidose/terapia , Amiloidose/genética , Amiloidose/metabolismo , Nefropatias/diagnóstico , Nefropatias/terapia , Nefropatias/genética , Proteômica/métodos , Espectrometria de Massas/métodos
7.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732004

RESUMO

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.


Assuntos
Produtos Finais de Glicação Avançada , Degeneração Macular , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Humanos , Produtos Finais de Glicação Avançada/metabolismo , Animais , Suínos , Retina/metabolismo , Retina/efeitos dos fármacos , Retina/patologia , Aminoácido Oxirredutases
9.
Acta Clin Belg ; 79(2): 97-102, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38454315

RESUMO

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.


Assuntos
Estações do Ano , Vitamina D , Humanos , Vitamina D/sangue , Vitamina D/análogos & derivados , Deficiência de Vitamina D/sangue
10.
Biomedicines ; 12(3)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38540181

RESUMO

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.

11.
Acta Clin Belg ; 79(2): 130-142, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38166537

RESUMO

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.


Assuntos
Insuficiência Renal Crônica , Proteína de Ligação a Vitamina D , Vitamina D , Humanos , Proteína de Ligação a Vitamina D/metabolismo , Proteína de Ligação a Vitamina D/genética , Insuficiência Renal Crônica/metabolismo , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Biomarcadores/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-38251780

RESUMO

Although warmth is a key sign of inflammatory skin lesions, an objective assessment and follow-up of the temperature changes are rarely done in dermatology. The recent availability of accurate, sensitive and cost-effective thermography devices has made the implementation of thermography in clinical settings feasible. The aim of this scoping review is to summarize the evidence around the value and pitfalls of infrared thermography (IRT) when used in the dermatology clinic. A systematic literature search was done for original articles using IRT in skin disorders. The results concerning the potential of IRT for diagnosis, severity staging and monitoring of skin diseases were collected. The data on the sensitivity and specificity of IRT were extracted. Numerous studies have investigated IRT in various skin diseases, revealing its significant value in wound management, skin infections (e.g. cellulitis), vascular abnormalities and deep skin inflammation (e.g. hidradenitis suppurativa). For other dermatological applications such as the interpretation of intradermal and patch allergy testing, hyper-/anhidrosis, erythromelalgia, cold urticaria and lymph node metastases more complex calculations, provocation tests or active cooling procedures are required. Dermatologists should be aware of a learning curve of IRT and recognize factors contributing to false positive and false negative results. Nonetheless, enough evidence is available to recommend IRT as a supplement to the clinical evaluation for the diagnosis, severity and follow-up of several skin diseases.

13.
Pigment Cell Melanoma Res ; 37(1): 74-80, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37753945

RESUMO

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.


Assuntos
Vitiligo , Humanos , Vitiligo/tratamento farmacológico , Resultado do Tratamento
14.
J Clin Med ; 12(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068480

RESUMO

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.

15.
Int J Mol Sci ; 24(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38069330

RESUMO

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.


Assuntos
Doenças Hematológicas , Hematologia , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectrofotometria Infravermelho/métodos , Doenças Hematológicas/diagnóstico
16.
Antioxidants (Basel) ; 12(12)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38136202

RESUMO

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.

17.
Adv Clin Chem ; 117: 53-102, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37973322

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo
18.
Crit Rev Clin Lab Sci ; : 1-23, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38013410

RESUMO

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.

19.
J Pers Med ; 13(10)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37888058

RESUMO

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

20.
J Pers Med ; 13(10)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37888118

RESUMO

Non-invasive scar management typically involves pressure therapy, hydration with silicones or moisturizers, and UV protection. Moisture loss from scars can lead to hypertrophic scar formation. Pressure therapy reduces blood flow, fibroblast activity, and transforming growth factor beta 1 (TGF-ß1) release. This study examined various moisturizers and liquid silicone gel's impact on microcirculation. 40 volunteers participated in a study where superficial abrasions were created to induce trans epidermal water loss (TEWL). Five moisturizers (TEDRA®, TEDRA® NT1, TEDRA® NT3, Alhydran®, Lipikar®) and BAP Scar Care® silicone gel were tested. TEWL, hydration, and blood flow were measured up to 4 h post-application. Results showed that silicone had the least impact on occlusion and hydration. Alhydran® reduced blood flow the most, while Lipikar® increased it the most. TEDRA® NT1 had reduced flow compared to TEDRA® and TEDRA® NT3. All TEDRA® products exhibited high hydration, and all but silicone showed good occlusion. Moisturizers influenced skin microcirculation, with some causing decrease, while others increased flow. However, the clinical impact on scarring remains unclear compared to the evident effects of hydration and occlusion. More research is necessary to study moisturizers alone and with pressure therapy on scars, along with potential adverse effects of increased microcirculation on scars.

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