Search Results (5,191)

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Plasma-activated water (PAW), enriched with reactive oxygen and nitrogen species (RONS), presents oxidative and antimicrobial characteristics with potential in cosmetic applications. This study examined the effects of two PAW formulations—nitrate-rich (PAW-N) and peroxide-rich (PAW-P)—on human hair types classified as straight (Type 1), wavy (Type 2), and coily/kinky (Type 4). The impact of PAW on hair structure and chemistry was evaluated using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), UV–Vis spectrophotometry, and physicochemical analyses of the liquids (pH, ORP, conductivity, and TDS). PAW-N, with high nitrate content (~500 mg/L), low pH (2.15), and elevated conductivity (6244 µS/cm), induced significant damage to porous hair types, including disulfide bond cleavage, protein oxidation, and lipid degradation, as indicated by FTIR and EDS data. SEM confirmed severe cuticle disruption. In contrast, PAW-P, containing >25 mg/L of hydrogen peroxide and exhibiting milder acidity and lower ionic strength, caused more localized and controlled oxidation with minimal morphological damage. Straight hair showed greater resistance to both treatments, while coily and wavy hair were more susceptible, particularly to PAW-N. These findings suggest that the formulation and ionic profile of PAW should be matched to hair porosity for safe oxidative treatments, supporting the use of PAW-P as a gentler alternative in hair care technologies. Full article

Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article

Background/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ Mthfr^677C>T mice to evaluate the effects of the TT genotype and low folate diets on embryonic development and MTHFR protein expression in pregnant mice. Methods: Female 677CC (mCC) and 677TT (mTT) mice were fed control (2 mg folic acid/kg (2D)), 1 mg folic acid/kg (1D) and 0.3 mg folic acid/kg (0.3D) diets before and during pregnancy. Embryos and maternal tissues were collected at embryonic day 10.5. Embryos were examined for developmental delays and defects. Methyltetrahydrofolate (methylTHF) and total homocysteine (tHcy) were measured in maternal plasma, and MTHFR protein expression was evaluated in maternal liver. Results: MethylTHF decreased due to the experimental diets and mTT genotype. tHcy increased due to 0.3D and mTT genotype; mTT 0.3D mice had significantly higher tHcy than the other groups. MTHFR expression was lower in mTT liver than mCC. MTHFR protein expression increased due to low folate diets in mCC mice, whereas in mTT mice, MTHFR expression increased only due to 1D. Developmental delays were increased in the litters of mTT mice fed 1D and 0.3D. Conclusions: The Mthfr^677C>T mouse models the effects of the MTHFR 677TT genotype in humans and provides a folate-responsive model for examination of the effects of folate intake and the MTHFR 677C>T variant during gestation. Full article

Objective: To characterize the profiles of resistance mutations to HIV reverse transcriptase inhibitors in Gabon. Design: Cross-sectional study conducted over 37 months, from October 2019 to October 2022, at the IST/HIV/AIDS Reference Laboratory, a reference center for the biological monitoring of people living with the human immunodeficiency virus (PWHIV) in Gabon. Methods: Plasma from 666 PWHIV receiving antiretroviral treatment was collected, followed by RNA extraction, amplification, and reverse transcriptase gene sequencing. Statistical analyses were performed using Stata^® 14.0 software (USA). Results: Six hundred and sixty-six (666) PWHIV plasma collected from 252 male and 414 female patients were analyzed and 1654 mutations were detected in 388 patients, including 849 (51.3%) associated with nucleoside reverse transcriptase inhibitors (NRTIs) and 805 (48.7%) with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Three of the most prescribed treatment regimens were associated to the appearance of both NRTIs and NNRTIs resistance mutations: TDF + 3TC + EFV (24.02%; 160/666); TDF + FTC + EFV) (17.2%; 114/666) and AZT + 3TC + EFV (14.6%; 97/666). Additionally, stage 3 of CD4 T-lymphocyte deficiency, the higher viral load, and treatment duration are risk factors influencing the appearance of virus mutations. Also, treatment containing TDF-3TC + DTG is more protective against mutations. Conclusions: Drug resistance mutations are common in Gabon and compromise the efficacy of ART. Further study must search for other causes of therapeutic failure in Gabon in PWHIV. Full article

This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2–coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage. Full article

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

Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35–75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values. Full article

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymatic disorder, affects over 500 million people worldwide and is often linked to exercise intolerance due to oxidative stress, but its true impact on physical performance remains unclear. This study aimed to evaluate the physiological and metabolic effects of G6PD deficiency on endurance capacity. Using humanized mice carrying the African G6PD variant [V68M; N126D] (hG6PD_A−), we show that despite reduced pentose phosphate pathway activity, these mice exhibit a 10.8% increase in treadmill critical speed (CS)—suggesting enhanced endurance capacity. Multi-omics profiling across red blood cells, plasma, skeletal muscle, spleen, kidney, and liver reveals metabolic adaptations, including elevated glycolysis, fatty acid oxidation, and increased mitochondrial activity, alongside heightened oxidative phosphorylation in muscle and accelerated red blood cell turnover in the spleen and liver. These findings indicate that systemic metabolic reprogramming may offset antioxidant deficiencies, potentially conferring a performance advantage. Given that G6PD deficiency affects up to 13% of African Americans and is associated with cardiovascular health disparities, our results challenge conventional exercise restrictions and highlight the need for personalized exercise guidelines for affected individuals. Full article

Background: Rheumatoid arthritis (RA) is an autoimmune disease that remains incurable. An increasing number of proteomic genome-wide association studies (GWASs) are emerging, offering immense potential for identifying novel therapeutic targets for diseases. This study aims to identify potential therapeutic targets for RA based on human plasma proteome. Methods: Protein quantitative trait loci were extracted and integrated from eight large-scale proteomic GWASs. Proteome-wide Mendelian randomization (Pro-MR) was performed to prioritize proteins causally associated with RA. Further validation of the reliability and stratification of prioritized proteins was performed using MR meta-analysis, colocalization, and transcriptome-wide summary-data-based MR. Subsequently, prioritized proteins were characterized through protein–protein interaction and enrichment analyses, pleiotropy assessment, genetically engineered mouse models, cell-type-specific expression analysis, and druggability evaluation. Phenotypic expansion analyses were also conducted to explore the effects of the prioritized proteins on phenotypes such as endocrine disorders, cardiovascular diseases, and other immune-related diseases. Results: Pro-MR prioritized 32 unique proteins associated with RA risk. After validation, prioritized proteins were stratified into four reliability tiers. Prioritized proteins showed interactions with established RA drug targets and were enriched in an immune-related functional profile. Four trans-associated proteins exhibited vertical or horizontal pleiotropy with specific genes or proteins. Genetically engineered mouse models for 18 prioritized protein-coding genes displayed abnormal immune phenotypes. Single-cell RNA sequencing data were used to validate the enriched expression of several prioritized proteins in specific synovial cell types. Nine prioritized proteins were identified as targets of existing drugs in clinical trials or were already approved. Further phenome-wide MR and mediation analyses revealed the effects and potential mediating roles of some prioritized proteins on other phenotypes. Conclusions: This study identified 32 plasma proteins as potential therapeutic targets for RA, expanding the prospects for drug discovery and deepening insights into RA pathogenesis. Full article

Pompe disease is a rare autosomal-recessive neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to the pathological accumulation of glycogen and impaired autophagy. Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) has been available since 2006, but may lead to the formation of anti-drug antibodies (ADAs) against the recombinant human enzyme, which, in turn, may adversely affect the response to ERT. Knowledge of the antigenic determinants of rhGAA involved in interaction with ADAs may facilitate the development of strategies to attenuate the anti-drug immune response in patients. Here, we determined the rhGAA ADA epitopes in the plasma of Pompe disease patients using a series of affinity purifications combined with epitope extraction and label free quantitation LC-MS. Full article

Background and aim: ANGPTL3 is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL) through its N-terminal domain. Besides this activity, the C-terminal domain of ANGPTL3 interacts with integrin αVβ3. Since integrins are involved in inflammation and in the initiation of atherosclerotic plaque, the aim of our study was to evaluate the potential direct pro-inflammatory action of ANGPTL3 through the interaction of the fibrinogen-like domain and integrin αVβ3. Methods: We utilized cultured THP-1 human-derived macrophages and evaluated their pro-inflammatory phenotype in response to treatment with human recombinant ANGPTL3 (hANGPTL3). By Western blot, RT-qPCR, biochemical analysis, and ELISA assays, we determined the expression of genes and proteins involved in lipid metabolism and inflammatory response as well as intracellular cholesterol and triglyceride levels. In addition, we evaluated the effect of hANGPTL3 on the cellular cholesterol efflux process. Results: Incubation of THP-1-derived macrophages with 100 ng/mL of hANGPTL3 increased the mRNA expression of the pro-inflammatory cytokines IL-1β, IL-6, and TNFα (respectively, 1.87 ± 0.08-fold, 1.35 ± 0.11-fold, and 2.49 ± 0.43-fold vs. control). The secretion of TNFα, determined by an ELISA assay, was also induced by hANGPTL3 (1.98 ± 0.4-fold vs. control). The pro-inflammatory effect of hANGPTL3 was partially counteracted by co-treatment with the integrin αVβ3 inhibitor RGD peptide, reducing the mRNA levels of IL-1β (3.35 ± 0.35-fold vs. 2.54 ± 0.25-fold for hANGPTL3 vs. hANGPTL3 + RGD, respectively). Moreover, hANGPTL3 reduced cholesterol efflux to apoA-I, with a parallel increase in the intracellular triglyceride and cholesterol contents by 31.2 ± 2.8% and 20.0 ± 4.1%, respectively, compared to the control. Conclusions: ANGPTL3 is an important liver-derived regulator of plasma lipoprotein metabolism, and overall, our results add a new important pro-inflammatory activity of this circulating protein. This new function of ANGPTL3 could also be related to triglyceride and cholesterol accumulation into macrophages. Full article

The scientific literature currently lacks studies that evaluate the nutritional composition of the tissues of cattle raised in different systems, so that the nutritional effects can be known and used to enhance consumption and use in the diet. The aim was therefore to assess whether the mineral content of muscle tissue (longissimus lumborum) in cattle finished during the rainy season in the Eastern Amazon is influenced by different farming systems. The treatments consisted of four systems (three pasture production systems and one feedlot system). 1. native wetland pasture in Santa Cruz do Arari (Mesoregion of Marajó); 2. native wetland pasture in Monte Alegre (Mesoregion of Baixo Amazonas); 3. cultivated dryland pasture in São Miguel do Guamá (Mesoregion of Nordeste Paraense); and 4. Confinement in Santa Izabel do Pará (Metropolitan Region of Belém). The analyses were carried out on samples of the longissimus lumborum muscle tissue of 48 male, castrated, crossbred Nelore cattle, twelve per breeding system, from commercial farms, destined for meat production, finished during the rainiest period of the year (between January and June). In systems 1 and 2, the animals were slaughtered in licensed slaughterhouses; the animals in systems 3 and 4 were slaughtered in commercial slaughterhouses. Food sampling and chemical analysis, soil sample collection and analysis, longissimus lumborum muscle tissue collection, sample preparation and digestion, and inductively coupled plasma optical emission spectrometry were evaluated. The experimental design was completely randomized in a linear model with four rearing systems and one period (rainy). The data was compared using the Statistical Analysis Systems (SAS) program. All analyses were carried out considering a significance level of 0.05. Samples of the diets offered (pasture and concentrate) were also collected. The Amazon systems influenced the macro- and micromineral content in the muscles of cattle (p < 0.05). The interaction between pasture systems vs. confinement showed differences in the minerals calcium (Ca), magnesium (Mg), phosphorus (P), copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn) (p < 0.05). However, there was no difference in the values of sodium (Na), potassium (K), and sulfur (S) between the rearing systems (p > 0.05). By contrast, the cultivated pasture system vs. extensive pasture showed differences in all the elements evaluated (p < 0.05). The rearing systems of the Eastern Amazon influenced the mineral content of beef, which continues to be an excellent source of macro- and microminerals and can compose the human diet. Full article

With the rapid progression of global industrialization and urbanization, emerging contaminants (ECs) have become pervasive in environmental media, posing considerable risks to ecosystems and human health. While multidisciplinary evidence continues to accumulate regarding their environmental persistence and bioaccumulative hazards, critical knowledge gaps persist in understanding their spatiotemporal distribution, cross-media migration mechanisms, and cascading ecotoxicological consequences. This review systematically investigates the global distribution patterns of ECs in aquatic environments over the past five years and evaluates their potential ecological risks. Furthermore, it examines the performance of various treatment technologies, focusing on economic cost, efficiency, and environmental sustainability. Methodologically aligned with PRISMA 2020 guidelines, this study implements dual independent screening protocols, stringent inclusion–exclusion criteria (n = 327 studies). Key findings reveal the following: (1) Occurrences of ECs show geographical clustering in highly industrialized river basins, particularly in Asia (37.05%), Europe (24.31%), and North America (14.01%), where agricultural pharmaceuticals and fluorinated compounds contribute disproportionately to environmental loading. (2) Complex transboundary pollutant transport through atmospheric deposition and oceanic currents, coupled with compound-specific partitioning behaviors across water–sediment–air interfaces. (3) Emerging hybrid treatment systems (e.g., catalytic membrane bioreactors, plasma-assisted advanced oxidation) achieve > 90% removal for recalcitrant ECs, though requiring 15–40% cost reductions for scalable implementation. This work provides actionable insights for developing adaptive regulatory frameworks and advancing green chemistry principles in environmental engineering practice. Full article

Oxidized phospholipids (OxPLs) are increasingly recognized as biologically active lipids involved in various pathologies. Both exposure to pathogenic factors and the efficacy of protective mechanisms are critical to disease development. In this study, we characterized an immunoassay that quantified the total capacity of the plasma to degrade or mask OxPLs, thereby preventing their interaction with cells and soluble proteins. OxLDL-coated plates were first incubated with human blood plasma or a control vehicle, followed by an ELISA using a monoclonal antibody specific to oxidized phosphatidylethanolamine. Pretreatment with the diluted blood plasma markedly inhibited mAb binding. The masking assay was optimized by evaluating the buffer composition, the compatibility with various anticoagulants, potential interfering compounds, the kinetic parameters, pre-analytical stability, statistical robustness, and intra- and inter-individual variability. We propose that this masking assay provides a simple immunological approach to assessing protective mechanisms against lipid peroxidation products. Establishing this robust and reproducible method is essential for conducting clinical association studies that explore masking activity as a potential biomarker of the predisposition to a broad range of lipid-peroxidation-related diseases. Full article