Search Results (158)

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

Encephalitozoon cuniculi causes both clinical and subclinical infections in rabbits, complicating a diagnosis due to the limitations of conventional tools like ELISA. This study analyzes serum proteomic profiles across clinical, subclinical, and healthy rabbits to identify discriminatory biomarkers. Serum from 90 pet rabbits (30 per group) was pooled (10 samples per pool, 3 pools per group) and analyzed using one-dimensional gel electrophoresis and mass spectrometry. The proteomic analysis revealed 109, 98, and 74 proteins expressed in healthy, subclinical, and clinical groups, respectively. Of these, 50, 40, and 33 proteins were unique to the healthy, subclinical, and clinical groups, respectively, with only 10 proteins shared across all. A total of 88 proteins were differentially expressed in infected groups compared to healthy controls. Importantly, 12 proteins were consistently upregulated in both subclinical and clinical infections. These include markers related to the immune response (beta-2-microglobulin, alpha-2-HS-glycoprotein), coagulation (antithrombin-III, alpha-1-antiproteinase S-1), vitamin A transport (retinol-binding proteins), lipid metabolism (apolipoprotein C-III), cytoskeletal regulation (actin-depolymerizing factor), extracellular matrix integrity (fibrillin 2), and oxidative stress (monooxygenase DBH-like 1). Additionally, Gc-globulin and ER lipid-raft-associated 1 were linked to immune modulation and signaling. These findings identify specific serum proteins as promising biomarkers for distinguishing subclinical from clinical encephalitozoonosis in rabbits, enabling an early diagnosis and effective disease monitoring. Full article

Previous studies have suggested that T14, a 14-amino-acid peptide derived from acetylcholinesterase (AChE), functions as an activity-dependent signalling molecule with key roles in brain development, and its dysregulation has been linked to neurodegeneration in Alzheimer’s disease. In this study, we examined the distribution of T14 under normal developmental conditions in the mouse forebrain, motor cortex (M1), striatum (STR), and substantia nigra (SN). T14 immunoreactivity declined from E16 to E17 and further decreased by P0, then peaked at P7 during early postnatal development before declining again by adulthood at P70. Lower T14 immunoreactivity in samples processed without Triton indicated that T14 is primarily localised intracellularly. To explore the relationship between T14 expression and neuronal activity, we used mouse models with chronic silencing (Rbp4Cre-Snap25), acute silencing (Rbp4Cre-hM4Di), and acute activation (Rbp4Cre-hM3D1). Chronic silencing altered the location and size of intracellular T14-immunoreactive particles in adult brains, while acute silencing had no observable effect. In contrast, acute activation increased T14+ density in the STR, modified T14 puncta size near Rbp4Cre cell bodies in M1 layer 5 and their projections to the STR, and enhanced co-localisation of T14 with presynaptic terminals in the SN. Full article

The increasing number of individuals with chronic kidney disease (CKD), mainly due to lifestyle changes—such as increased consumption of processed foods, physical inactivity, obesity, and smoking habits—and population aging, highlights the need to identify new biomarkers to facilitate monitoring of CKD progression and, consequently, predict end-stage renal disease (ESRD). This study aimed to analyze the proteomic profile of urine samples from healthy individuals and those with ESRD to identify potential biomarkers for this advanced stage of CKD. Urine samples were collected from 20 participants, comprising 10 healthy individuals and 10 patients with ESRD, and analyzed via liquid chromatography coupled with a tandem mass spectrometer. Bioinformatics analyses, including gene ontology and protein interaction, were subsequently conducted. A total of 416 proteins were identified in the proteomic profiles of the groups, and 19 proteins showed statistically significant differences between them. Of these, five proteins—hemopexin, beta-2-microglobulin, retinol-binding protein 4, transthyretin, and factor D—emerged as potential biomarkers for ESRD. The proteins identified were able to characterize and differentiate the urinary proteomic profiles of the two groups. The five selected proteins represent promising candidates for ESRD biomarkers. Full article

Vitamin A (retinol) and its derivatives (retinoids) assume critical roles in neural development, cellular differentiation, axon elongation, programmed cell apoptosis and various fundamental cellular processes. Retinoids function by binding to specific nuclear receptors, such as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), activating specific signalling pathways in the cells. The disruption of the retinoic acid signalling pathway can result in neuroinflammation, oxidative and ER stress and mitochondrial dysfunction and has been implicated in a wide range of neurodegenerative diseases. The present study explored the potential therapeutic application of our innovative CNS-permeable synthetic retinoid, Ellorarxine, for the treatment of neurodegenerative disorders in vitro. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay, lactate dehydrogenase (LDH) assay, enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and immunofluorescence staining were performed. Ellorarxine increased Cyp26 and, selectively, RARβ protein expression in neurons, glia and microglia. Ellorarxine significantly reduced cell death (neurons, glia), increased mitochondrial viability (neurons), modulated cytokine release (microglia), and positively regulated cellular autophagy (neurons, glia, microglia). These results suggest that Ellorarxine is a promising drug candidate that should be further investigated in the treatment of neurodegenerative diseases. Full article

Previous studies have shown that high-dose vitamin supplements can improve vaccine-induced immune responses and pathogen protection in the context of vitamin deficiencies. To further elucidate the influence of vitamin supplements on immune responses toward pediatric vaccines, we performed a randomized controlled clinical trial (PCVIT) of 20 healthy children 1–4 years of age in Memphis, Tennessee. Study participants received a booster vaccine for pneumococcus and a primary vaccine for hepatitis A virus with or without a high-dose, oral, liquid supplement of 10,000 IU retinyl palmitate. We found that the children enrolled in PCVIT had higher baseline vitamin levels than previously described older children and adults living in Memphis. Only one child in PCVIT had a serum retinol level of less than 0.3 µg/mL. The children frequently consumed milk and baby foods that were likely vitamin-fortified, providing an explanation for the relatively high vitamin levels. Most children in PCVIT responded well to pneumococcus and hepatitis A vaccines by pathogen-specific antibody upregulation. The one child with a serum retinol level below 0.3 µg/mL did not receive a vitamin supplement and exhibited the lowest fold-change in antibody responses toward pneumococcal serotypes. A correlation matrix encompassing demographics, vitamin levels, vaccine-induced immune responses, C-reactive protein, and total serum immunoglobulin isotypes, including IgG2 and IgA, identified variables associated with vaccination outcomes. Perhaps because children were predominantly retinol-sufficient at baseline, the high-dose vitamin A supplement exhibited no benefit to vaccine-induced immune responses. In fact, when vitamin supplemented and vitamin unsupplemented groups were compared among participants with the highest baseline retinol levels, there was a trend toward weaker vaccine-induced immune responses in the vitamin supplemented group. Results encourage the performance of larger clinical studies before high-dose vitamin supplements are recommended for populations that are otherwise vitamin-replete. Full article

Background: This prospective study aimed to evaluate renal function using retinol binding protein 4 (RBP4), cystatin C, and glomerular filtration rate (GFR) in relation to physical activity and lesion level in children with neurogenic bladder (NB) post-myelomeningocele. Methods: Two groups were studied: 33 children with NB and 20 healthy controls. Data collected included demographic details, physical activity levels, uroflowmetry, urodynamic diagnosis, and renal function parameters. Urinary RBP4 and serum cystatin C were measured using ELISA, and GFR was calculated using the Schwartz formula. Results: The NB group had higher median serum cystatin C and urinary RBP4/creatinine ratios compared to the control group (0.28 vs. 0.22; 18.6 vs. 3.2, respectively). The participants were categorized based on activity levels, lesion levels, catheterization status, and urodynamic diagnosis. No differences in RBP4, cystatin C, or urodynamic diagnosis were observed according to activity and lesion levels. Significant differences in GFR were found based on activity and lesion levels, with higher median GFR in NB children (182.7 vs. 147.3). No differences were found between catheterized and non-catheterized children in the studied parameters. Conclusions: Elevated urinary RBP4 in NB patients suggests possible proximal renal tubule dysfunction. Higher serum cystatin C despite lower creatinine levels indicates altered renal function in NB children. Urinary RBP4 correlates positively with bladder pressure at maximum cystometric capacity, suggesting potential utility in therapy monitoring and modification. Full article

Background: Retinol-binding protein 4 (RBP4) is primarily recognized for its role in retinoid transport, but has recently been implicated in cancer progression and prognosis. However, a comprehensive pan-cancer analysis of RBP4’s expression, prognostic significance, and functional associations across various cancers is lacking. Methods: We conducted a pan-cancer analysis of RBP4 using data from public databases. RBP4 expression levels were examined in 33 tumor types, and correlations with clinical outcomes, immune cell infiltration, DNA methylation, and gene mutations were assessed. Enrichment analyses of RBP4 and its co-expressed genes were performed to explore associated biological pathways. Additionally, in vitro experiments were conducted to assess the effects of RBP4 on cell migration and proliferation. Results: RBP4 showed differential expression between tumor and normal tissues, with downregulation in 21 cancer types and upregulation in 6. High expression levels of RBP4 were associated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in specific cancers, notably in BRCA, HNSC, and STAD, whereas it was a favorable prognostic factor in cancers such as KIRP and MESO. RBP4 expression was also associated with immune cell infiltration, particularly with CD4+ Th2 cells and immune checkpoint genes. DNA methylation analysis suggested that the methylation of RBP4 may play a role in its regulatory mechanisms across cancer types. Enrichment analyses revealed that RBP4 and its co-expressed genes are involved in metabolism-related pathways and immune regulation. Functional assays indicated that RBP4 knockdown promoted tumor cell migration and proliferation. Conclusions: This study provides a comprehensive pan-cancer analysis of RBP4, identifying its prognostic potential and possible involvement in tumor immunity and metabolism. Our findings suggest that RBP4 could serve as a novel biomarker and therapeutic target in cancer, although further experimental studies are required to elucidate its precise mechanisms in specific cancer types. Full article

Parathyroid hormone-related protein (PTHrP) and retinol-binding protein 4 (RBP4) have been associated with a worse prognosis of kidney disease. Recently, the direct interconnection between PTHrP and the peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor whose activation is nephroprotective, has been discovered. The aim of this study was to analyze the relationship between PTHrP, PPARγ, and RBP4. For this purpose, we analyzed the levels of these proteins, which were studied in the kidneys of five experimental groups of mice at 6 weeks of age: controls, diabetics, insulin-treated diabetics, transgenic mice overexpressing PTHrP at the renal level, and the latter mice that were also induced with diabetes. In addition, we also analyzed the expression levels of these molecules in two mouse podocyte cell lines, controls and PPARγKO, subjected to a lipotoxic insult by palmitic acid. We found that RBP4 and PTHrP are increased in the kidney in pathological conditions and that insulin and PPARγ act regulating PTHrP and RBP4 expression, suggesting that the regulation of this system is critical for the maintenance of renal homeostasis and how it becomes imbalanced in different pathophysiological conditions. Full article

The protein therapeutics market, including antibody and fusion proteins, has experienced steady growth over the past decade, underscoring the importance of optimizing amino acid sequences. In our previous study, we developed a fusion protein, R31, which combines retinol-binding protein (RBP) with albumin domains IIIA and IB, linked by a sequence (AAAA), and includes an additional disulfide bond (N227C-V254C) in IIIA. This fusion protein effectively inhibited hepatic stellate cell activation. In this study, we further optimized the sequence. The G176K mutation at the C-terminus of RBP altered the initiation site of the first α-helix in domain IIIA, shifting it from P182 to K176, and promoted polar interactions between K176 and adjacent residues, enhancing the rigidity of the RBP/IIIA interface. The introduction of an additional disulfide bond (V231C/Y250C) connecting helices 3 and 4 in IIIA resulted in a three-fold increase in productivity and a 2 °C improvement in thermal stability compared to R31. Furthermore, combining the G176K mutation with V231C/Y250C further enhanced both productivity and anti-fibrotic activity. These findings suggest that the enhanced stability of domain IIIA, conferred by V231C/Y250C, along with the increased rigidity of the RBP/IIIA interface, optimizes interdomain distance and alignment, facilitating proper protein folding. Full article

Background/Objectives: Dietary protein intake can potentially influence renal function. This study aimed to elucidate the association between dietary protein supplementation and a decrease in the estimated glomerular filtration rate (eGFR) in Japanese stroke patients undergoing rehabilitation. Methods: From July 2017 to June 2021, 60 patients undergoing post-stroke rehabilitation were randomly assigned to a rehabilitation alone or rehabilitation nutrition group, which received 120 g Reha-Time Jelly^® after each session. Both groups were followed up for 3 months. Serum nutritional markers (prealbumin and retinol-binding protein), muscle strength, body composition, renal function markers (eGFR based on creatinine [eGFR-Cr] and cystatin C [eGFR-Cys]), urinary protein-to-creatinine ratio (UPCR), and motor function (walking speed, 2-min walk distance, and chair stand test) were assessed at baseline and post-intervention. Results: Of the 60 participants (mean age: 70.2 ± 10.0 years), 39 were men (65.0%) and 19 (31.7%) had chronic kidney disease. Initial eGFR-Cr and eGFR-Cys values were 70.5 ± 17.2 and 66.6 ± 14.8 mL/min/1.73 m², respectively. After the intervention, the rehabilitation nutrition group demonstrated a significantly greater increase in body mass index (BMI) and a smaller decrease in bone mineral content than the rehabilitation alone group. However, no significant between-group differences were noted in serum marker levels or motor function, including grip strength and knee extensor strength, on the paralyzed and non-paralyzed sides. The change in chair stand test performance indicated a trend toward improvement in the rehabilitation nutrition group. No significant differences were observed in the changes in renal function. Conclusions: A 3-month nutritional supplementation intervention may help increase BMI, preserve bone mineral content, and support physical activity levels in patients undergoing post-stroke rehabilitation without negatively affecting renal function. Full article

Recently malaria and micronutrient deficiencies have become a major worldwide public health problem, particularly in Africa and other endemic countries with children under 5 years old being the most vulnerable. Apart from nutritional problems that cause micronutrient deficiencies, studies have also reported that parasitic infections like malaria can affect the levels of micronutrients. Thus, this research was aimed at assessing the serum levels of micronutrient biomarkers and their association with malaria infection in children under 5 years old in the Buea Health District. Method: This cross-sectional study recruited 80 participants from February to April 2024. The micronutrient biomarkers levels were measured using a Q-7plex Human Micronutrient Measurement Kit. Results: There were changes in serum micronutrient biomarkers levels between malaria infected and healthy children. Ferritin was higher in sick children (23.53 μg/L ± 7.75) than in healthy children (19.07 μg/L ± 3.87), significantly (p < 0.002). The same trend was observed with the soluble transferrin receptor being higher (p < 0.049) in sick children (3.74 mg/L ± 1.92) compared to healthy ones (3.08 mg/L ± 0.64). In addition, the levels of retinol-binding protein 4 and thyroglobulin levels were not significantly different between the sick and healthy children. Therefore, this study revealed that malaria causes alterations in the serum levels of micronutrient biomarkers and consequently affects micronutrient levels in children below the age of 5 in the Buea Health District. Full article

Background: Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is largely driven by obesity-related factors, including adipokines and bioactive peptides primarily secreted by the adipose tissue, such as leptin, adiponectin, and resistin. These molecules link metabolic dysregulation to cardiovascular dysfunction, influencing HFpEF progression and patient outcomes Methods: A comprehensive literature search was conducted in PubMed up to 20 November 2024, using keywords and MeSH terms, such as “HFpEF”, “adipokines”, “leptin”, “adiponectin”, and “resistin”, yielding 723 results. Boolean operators refined the search, and reference lists of key studies were reviewed. After screening for duplicates and irrelevant studies, 103 articles were included, providing data on adipokines’ roles in HFpEF pathophysiology, biomarkers, and therapeutic implications. Results: Both preclinical and clinical studies have demonstrated that adipokines play a role in modulating cardiovascular function, thereby contributing to the development of cardiometabolic HFpEF. Leptin promotes myocardial hypertrophy, fibrosis, endothelial dysfunction, and inflammation, though contradictory evidence suggests potential cardioprotective roles in subgroups like obese African American women. Adiponectin generally offers protective effects but presents a paradox, where elevated levels may correlate with worse outcomes, which may reflect either a compensatory response to cardiac dysfunction or a maladaptive state characterized by adiponectin resistance. Resistin is associated with increased cardiovascular risk through pro-inflammatory and pro-fibrotic effects, though its role in HFpEF requires further clarification. Other adipokines, like retinol-binding protein 4 and omentin-1, have emerged as potential contributors. Despite growing insights, clinical translation remains limited, underscoring a significant gap between experimental evidence and therapeutic application. Conclusions: Future research should focus on targeted interventions that modulate adipokine pathways to potentially improve HFpEF outcomes. Innovative treatment strategies addressing underlying metabolic disturbances and adipokine dysregulation are essential for advancing the management of this challenging condition. Full article

Background and Objectives: The relationship between circulating retinol-binding protein 4 (RBP4) levels and hepatitis C virus (HCV) infection remains unclear. This study aims to systematically assess RBP4 expression in patients with HCV and its correlation with disease severity. Materials and Methods: We searched the Embase, PubMed, and Cochrane databases for relevant studies up to 1 January 2024. This study was registered on PROSPERO (CRD42023489051). Results: Our analysis included eight studies with 2612 participants (1152 controls and 1282 patients with HCV). Overall, RBP4 levels did not significantly differ between patients with HCV and controls (SMD: −0.36; 95% CI: −0.94, 0.23; p = 0.23). However, in a subgroup of Asian subjects, patients with HCV showed significantly lower RBP4 levels (SMD: −0.40; 95% CI: −0.49, −0.31; p = 0.10). Additionally, a negative correlation between RBP4 levels and disease severity was observed across all studied populations. Conclusions: RBP4 levels may vary due to HCV genotype, ethnicity, and environmental factors. In the context of HCV infection, RBP4 levels appear to reflect the severity of disease progression. Our findings indicate that RBP4 could serve as a biomarker for HCV disease progression. Further research is needed to elucidate the complex mechanisms of RBP4 in HCV infection. Full article

The fragmented forests of the Kenya highlands, known for their exceptional species richness and endemism, are among the world’s most important biodiversity hotspots. However, detailed studies on the fauna of these ecosystems—especially specialist species that depend on moist forests, which are particularly threatened by habitat fragmentation—are still limited. In this study, we used mitochondrial genes (cytochrome b and the displacement loop) and a nuclear marker (retinol-binding protein 3) to investigate genetic and morphological diversity, phylogenetic associations, historical divergence, population dynamics, and phylogeographic patterns in two rodent species—the soft-furred mouse (Praomys jacksoni) and the African wood mouse (Hylomyscus endorobae)—across Kenya’s forest landscapes. We found a complex genetic structure, with P. jacksoni exhibiting greater genetic diversity than H. endorobae. The Mt. Kenya P. jacksoni populations are significantly genetically different from those in southwestern forests (Mau Forest, Kakamega Forest, and Loita Hills). In contrast, H. endorobae presented no observable biogeographic structuring across its range. The genetic diversity and geographic structuring patterns highlighted selectively strong effects of forest fragmentation and differing species’ ecological and evolutionary responses to these landscape changes. Our findings further underscore the need for expanded sampling across Kenya’s highland forests to better understand species’ changing diversity and distribution patterns in response to the impacts of human-mediated habitat changes. These insights are critical for informing conservation strategies to preserve biodiversity better in this globally important region. Full article