Search Results (1,666)

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

The scalability and processability of high-performance membranes remain significant challenges in membrane technology. This work focuses on optimizing the pilot-scale production of patterned polysulfone (PSf) ultrafiltration membranes using the spray-modified non-solvent-induced phase separation (s-NIPS) method on a roll-to-roll pilot line. s-NIPS has already been studied extensively at lab-scale to prepare patterned membranes for various applications including membrane bioreactors (MBR), reverse osmosis (RO) and forward osmosis (FO). Although studied at the lab scale, membranes prepared at a larger scale can significantly differ in performance; therefore, phase inversion parameters, including polymer concentration, molecular weight, and additive type (i.e., polyethylene glycol (PEG) or polyvinylpyrolidine (PVP)) and concentration, were systematically varied when casting on a roll-to-roll, 12″ wide pilot line to identify optimal conditions for achieving defect-free, high-performance, patterned PSf membranes. The membranes were characterized for their pure water permeance, BSA rejection, casting solution viscosities, and resulting morphology. s-NIPS patterned membranes exhibit 150–350% increase in water flux as compared to their reference flat membrane, thanks to very high pattern heights up to 825 µm and formation of finger-like macrovoids. This work bridges the gap between lab-scale and pilot-scale membrane preparation, while proposing an upscaled membrane with great potential for use in water treatment. Full article

Theranostic agents enable the simultaneous diagnosis and treatment of diseases, and they are particularly useful in fluorescent imaging and cancer therapies. In this study, carbon quantum dots were synthesized via a microwave-assisted method using citric acid and bovine serum albumin (BSA) as precursors. The resulting CQDs exhibited spherical morphology, an average size of 4 nm, and an amorphous graphitic structure. FT-IR characterization revealed the presence of amide bonds and oxygenated functional groups. At the same time, optical analysis showed excitation at 320 nm and emission between 360 and 400 nm, with fluorescent stability maintained for one month. Furthermore, the CQDs demonstrated good thermal stability and photothermal efficiency, reaching temperatures above 41 °C within 15 min under NIR irradiation, with a mass loss of less than 1%. Their stability was evaluated in media with different pH levels, simulating physiological and tumor environments. While their behavior was affected under acidic conditions, their excellent photothermal conversion capacity and overall stability in triple-distilled water positioned them as promising candidates for theranostic applications in cancer, effectively combining diagnostic imaging and thermal therapy. Full article

Drug resistance remains a critical barrier to effective treatment in several cancers, particularly triple-negative breast cancer (TNBC). Estrogen receptor α36 (ERα36), a variant of the estrogen receptor in ER-negative breast cancer cells, plays important roles in cancer cell proliferation. We investigated the role of ERα36 in regulating multidrug resistance protein 1 (MDR1) in MDA-MB-231 human breast cancer cells. The activation of ERα36 by BSA-conjugated estradiol (BSA-E2) increased cell viability under Adriamycin exposure, suggesting its involvement in promoting drug resistance. BSA-E2 treatment significantly reduced the intracellular rhodamine-123 levels by activating the MDR1 efflux function, which was linked to increased MDR1 transcription and protein expression. The mechanical ERα36-mediated BSA-E2-induced activation of EGFR and downstream signaling via c-Src led to an activation of the Akt/ERK pathways and transcription factors, NF-κB and CREB. Additionally, ERα36 is involved in activating Wnt/β-catenin pathways to induce MDR1 expression. The silencing of ERα36 inhibited the BSA-E2-induced phosphorylation of Akt and ERK, thereby reducing MDR1 expression via downregulation of NF-κB and CREB as well as Wnt/β-catenin signaling. These findings demonstrated that ERα36 promotes MDR1 expression through multiple non-genomic signaling cascades, including Akt/ERK-NF-κB/CREB and Wnt/β-catenin pathways, and highlight the role of ERα36 as a promising target to enhance chemotherapeutic efficacy in TNBC. Full article

Background: Psoriasis is a chronic inflammatory skin disease linked to systemic comorbidities, including metabolic, cardiovascular, and autoimmune disorders. Thyroid dysfunction, particularly hypothyroidism, has been observed in patients with moderate-to-severe psoriasis, suggesting possible shared inflammatory pathways. Objectives: This study aims to explore the relationship between psoriasis and thyroid dysfunction in adults with moderate-to-severe psoriasis undergoing biologic therapy to determine whether psoriasis predisposes individuals to thyroid disorders and to identify demographic or clinical factors influencing this association. Materials and Methods: A cross-sectional study included adult patients with moderate-to-severe psoriasis receiving biologic therapy, recruited from the Psoriasis Unit at the Dermatology Department of Hospital Universitario San Cecilio in Granada, Spain, from 2017 to 2023. Patients with mild psoriasis or those treated with conventional systemic therapies were excluded. The data collected included demographics and clinical characteristics, such as age, sex, BMI (body mass index), and psoriasis severity (psoriasis severity was evaluated using the Psoriasis Area Severity Index (PASI), body surface area (BSA) involvement, Investigator’s Global Assessment (IGA), pruritus severity using the Numerical Rating Scale (NRS), and impact on quality of life through the Dermatology Life Quality Index (DLQI)). Thyroid dysfunction, including hypothyroidism and subclinical hypothyroidism, was assessed based on records from the Endocrinology Department. Results: Thyroid dysfunction was found in 4.2% of patients, all classified as hypothyroidism, primarily subclinical. The affected patients were generally older, with a mean age of 57.4 years. No significant differences in psoriasis severity (PASI, BSA) or treatment response were observed between patients with and without thyroid dysfunction. Conclusion: Our findings suggest hypothyroidism is the main thyroid dysfunction in psoriatic patients, independent of psoriasis severity. The lack of impact on psoriasis severity suggests hypothyroidism may be an independent comorbidity, warranting further research into shared inflammatory mechanisms. Full article

Background/Objectives: Enzymatic debridement with NexoBrid^® is an effective alternative to surgical debridement in burn care, but its potential systemic effects remain unclear. In the context of personalized burn care, understanding individual patient responses to topical agents is essential to optimize outcomes and minimize risks. This study aimed to characterize laboratory and clinical parameter changes following NexoBrid^® application in patients with small burn injuries (≤10% TBSA). Methods: We retrospectively analyzed 75 burn patients treated with NexoBrid^® to evaluate changes in systemic inflammatory markers, coagulation parameters, and clinical parameters before and after enzymatic debridement. Results: Statistically significant increases in body temperature (p = 0.018), decreases in hemoglobin (p < 0.001), and increases in C-reactive protein (CRP) levels (p < 0.001) were observed, suggesting mild systemic inflammatory changes. However, leukocyte counts did not change significantly (p = 0.927), and body temperature remained within the normothermic range, indicating that these changes were not clinically significant. A significant decrease in the prothrombin time ratio (% of normal; p = 0.002) was also observed, suggesting potential impacts on coagulation. Importantly, while body temperature was slightly higher in patients with a higher degree of BSA exposure within the ≤10% TBSA cohort (p = 0.036), the extent of NexoBrid^® application did not correlate with other inflammatory markers. Conclusions: These findings suggest that measurable systemic changes can occur following NexoBrid^® application in small burns, particularly affecting inflammatory and coagulation parameters. These observations contribute to the understanding of treatment-related responses and may help inform clinical decision-making. Full article

There are currently no approved therapeutic treatments targeting metabolic dysfunction-associated steatotic liver disease (MASLD). Albumin, a liver-produced plasma protein with anti-inflammatory and antioxidant properties, is reduced in advanced liver disease. Considering the role of chronic obesity-induced inflammation in MASLD pathogenesis, we investigated whether albumin administration could prevent disease progression to metabolic dysfunction-associated steatohepatitis (MASH). MASLD was induced in mice using a high-fat and high-cholesterol (PC) treatment for 8 weeks, followed by treatment with bovine serum albumin (BSA; 0.8 mg/kg) every three days for another 8 weeks. This regimen prevented time-dependent weight gain, regardless of diet, with 57% and 27% reductions in mice fed a standard chow (Std Chow) or PC diet, respectively. Further, supplementation reduced nuclear factor kappa B (NF-κB) activation by 2.8-fold (p = 0.0328) in PC-fed mice, consistent with albumin’s known anti-inflammatory properties. Unexpectedly, albumin also reduced hepatic neutral lipid accumulation and circulating non-esterified fatty acids. While PC-fed mice did not exhibit full progression to MASH, albumin treatment significantly increased hepatic matrix metalloproteinase-2 expression, suggesting the inhibition of early fibrotic signalling. While further studies are needed to elucidate the underlying mechanisms, these findings offer new insight into the potential of albumin, either alone or in combination with other therapies, to reduce hepatic steatosis in MASLD. Full article

Dietary advanced glycation end-products (dAGEs) contained in high-sugar/fat and ultra-processed foods of the “Western diet” (WD) pattern predispose to several diseases by altering protein function or increasing oxidative stress and inflammation via RAGE (receptor for advanced glycation end-products). Although elevated endogenous AGEs are associated with loss of muscle mass and functionality (i.e., muscle wasting; MW), the impact of dAGEs on MW has not been elucidated. Here, we show that the most common dAGEs or their precursor, methylglyoxal (MGO), induce C2C12 myotube atrophy as endogenous AGE-derived BSA. ROS production, mitochondrial dysfunction, mitophagy, ubiquitin–proteasome activation, and inhibition of myogenic potential are common atrophying mechanisms used by MGO and AGE-BSA. Although of different origins, ROS are mainly responsible for AGE-induced myotube atrophy. However, while AGE-BSA activates the RAGE-myogenin axis, reduces anabolic mTOR, and causes mitochondrial damage, MGO induces glycolytic stress and STAT3 activation without affecting RAGE expression. Among thirty selected natural compounds, Vaccinium macrocarpon (VM), Camellia sinensis, and chlorophyll showed a surprising ability in counteracting in vitro AGE formation. However, only the standardized VM, containing anti-glycative metabolites as revealed by UHPLC-HRMS analysis, abrogates AGE-induced myotube atrophy. Collectively, our data suggest that WD-linked dAGE consumption predisposes to MW, which might be restricted by VM food supplements. Full article

Fruit size is an important agronomic trait affecting the yield and commercial value of melon and a key trait selected for during domestication. In this study, two respective melon accessions (large-fruited M202008 and small-fruited M202009) were crossed, and developed biparental mapping populations of the F₂ generation (160 and 382 plants) were checked across two subsequent experimental years (2023 and 2024). The phenotypic characterization and genetic inheritance analysis showed that melon fruit size is modulated by quantitative genetics. Bulked segregant sequencing analysis (BSA-seq) identified a stable and effective quantitative trait locus (QTL, named Cmfs) controlling fruit size, localized to a 3.75 Mb region on chromosome 9. To better delineate the main-effect Cmfs locus, co-dominant polymorphic molecular markers were developed in this genetic interval, and genotyping was performed within the F₂ mapping populations grown across two years. QTL analysis of the phenotypic and genotypic datasets delimited the major-effect Cmfs locus interval for fruit length [2023: logarithm of odds (LOD) value = 6.16, 16.20% phenotypic variation explained (PVE); 2024: LOD = 5.44, 6.35% PVE] and fruit diameter (2023: LOD value = 5.48, 14.59% PVE; 2024: LOD = 6.22, 7.22% PVE) to 1.88 and 2.20 Mb intervals, respectively. The annotation analysis across the melon genome and comparison of resequencing data from the two parental lines led to the preliminary identification of MELO3C021600.1 (annotated as cytochrome P450 724B1) as a candidate gene related to melon fruit size. These results provide a better understanding for further fine mapping and functional gene analysis related to melon fruit size. Full article

Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic consequences of BSA deprivation during preimplantation stages in mice. Embryos cultured in BSA-free media during specific time windows exhibited impaired blastocyst formation, with continuous deprivation from the two-pronuclei (2PN) stage significantly reducing trophectoderm (TE) and inner cell mass (ICM) cell numbers (p < 0.05), indicating compromised viability. Short-term BSA deprivation similarly disrupted lineage allocation, underscoring the sensitivity of early embryos to nutrient availability during cell fate determination. Although birth rates remained unaffected, suggesting compensatory mechanisms, longitudinal analysis revealed sex-specific metabolic dysfunction. Male offspring developed progressive glucose intolerance by 16 weeks, exhibiting elevated fasting glucose levels (p < 0.05) and impaired glucose clearance, whereas females showed no significant alterations in glucose metabolism. This study demonstrates that protein restriction during the preimplantation period not only disrupts early embryonic development but also programs long-term metabolic dysfunction, underscoring the importance of optimizing culture conditions in assisted reproductive technologies to minimize future health risks. Full article

Recent studies have increasingly focused on molecular interactions between small molecules and proteins, especially binding mechanisms and thermodynamics, using multispectroscopic and molecular dynamics approaches. This study elucidated the molecular interaction mechanism between bovine serum albumin (BSA) and trans-resveratrol (Res) through an integrated approach combining multispectroscopic analyses and molecular dynamics simulations. The fluorescence quenching study revealed a static quenching mechanism between BSA and Res, which was further confirmed via ultraviolet–visible (UV-Vis) absorption spectroscopy. In particular, K_SV decreased from 5.01 × 10⁴ M⁻¹ at 298 K to 3.99 × 10⁴ M⁻¹ at 318 K. Furthermore, the calculated K_q values significantly exceeded 1 × 10¹² M⁻¹ s⁻¹. With increasing Res concentration, the peak fluorescence intensities of Tyr and Trp residues both exhibited a blue shift. The α-helix content of the BSA–Res complex was 59.8%, slightly lower than that of BSA (61.3%). Res was found to bind to site I in subdomain IIA of BSA. The molecular dynamics simulation also identified the specific binding of Res to site I of BSA, while thermodynamic studies revealed that the binding process occurs spontaneously and is primarily mediated by hydrogen bonding interactions. These findings not only enrich the theoretical framework of small-molecule–protein interactions but also provide a crucial scientific foundation for the development and utilization of natural products. Full article

Early diagnosis of Alzheimer’s disease (AD) is essential for effective treatment; however current diagnostic methods are often complex, costly, and unsuitable for point-of-care testing. Graphene-based biosensors offer an alternative due to their affordability, versatility, and high conductivity. However, graphene’s conductivity can be compromised when its carbon lattice is oxidized to introduce functional groups for biomolecule immobilization. This study addresses this challenge by developing an electrochemical immunosensor using carboxyl-modified commercial graphene foam (COOH-GF) electrodes. The conductivity of graphene is preserved by enabling efficient COOH modification through π–π non-covalent interactions, while antibody immobilization is optimized via EDC-NHS carbodiimide chemistry. The immunosensor detects tau-441, an AD biomarker, using differential pulse voltammetry (DPV), achieving a detection range of 1 fM–1 nM, with a limit of detection (LOD) of 0.14 fM both in PBS and human serum. It demonstrates high selectivity against other AD-related proteins, including tau-217, tau-181, amyloid beta (Aβ_1-40 and Aβ_1-42), and 1% BSA. These findings underscore its potential as a highly sensitive, cost-effective tool for early AD diagnosis. Full article

Planar heaters are designed to deliver uniform heat across broad surfaces and serve as critical components in applications requiring energy efficiency, safety, and mechanical flexibility, such as wearable electronics and smart textiles. However, conventional metal-based heaters are limited by poor adaptability to curved or complex surfaces, low mechanical compliance, and susceptibility to oxidation-induced degradation. To overcome these challenges, we applied a protein-assisted electroless copper (Cu) plating strategy to electrospun poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) nanofiber substrates to fabricate flexible, conductive planar heating membranes. For interfacial functionalization, a protein-based engineering approach using bovine serum albumin (BSA) was employed to facilitate palladium ion coordination and seed formation. The resulting membrane exhibited a dense, continuous Cu coating, low sheet resistance, excellent durability under mechanical deformation, and stable heating performance at low voltages. These results demonstrate that the BSA-assisted strategy can be effectively extended to complex three-dimensional fibrous membranes, supporting its scalability and practical potential for next-generation conformal and wearable planar heaters. Full article

Background/Objectives: Understanding the molecular interactions between small bioactive compounds and serum albumins is essential for drug development and pharmacokinetics. Noraucuparin, a biphenyl-type phytoalexin with promising pharmacological properties, has shown a strong binding affinity to bovine serum albumin (BSA), a model protein for drug transport. This study aims to elucidate the structural and energetic characteristics of the noraucuparin–BSA complex under physiological and slightly elevated temperatures. Methods: Microsecond-scale molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born Surface Area (MMGBSA)-binding-free energy calculations were performed to investigate the interaction between noraucuparin and BSA at 298 K and 310 K. Conformational flexibility and per-residue energy decomposition analyses were conducted, along with interaction network mapping to assess ligand-induced rearrangements. Results: Noraucuparin preferentially binds to site II of BSA, near the ibuprofen-binding pocket, with stabilization driven by hydrogen bonding and hydrophobic interactions. Binding at 298 K notably increased the structural mobility of BSA, affecting its global conformational dynamics. Key residues, such as Trp213, Arg217, and Leu237, contributed significantly to complex stability, and the ligand induced localized rearrangements in the protein’s intramolecular interaction network. Conclusions: These findings offer insights into the dynamic behavior of the noraucuparin–BSA complex and enhance the understanding of serum albumin–ligand interactions, with potential implications for drug delivery systems. Full article

Coumarins are known for interacting with proteins and exhibiting diverse biological activities. This study investigates the interaction between coumarin-343 (C343) and human (HSA) and bovine (BSA) serum albumins. Fluorescence spectroscopy and theoretical simulations, including density functional theory (DFT) and molecular docking, were used to analyze the ligand–protein complex formation. The fluorescence quenching data revealed that C343 binds to both proteins, with binding constants of 2.1 × 10⁵ mol·L⁻¹ (HSA) and 6.5 × 10⁵ mol·L⁻¹ (BSA), following a 1:1 stoichiometry. Binding site markers identified drug site I (DS1), located in subdomain IIA, as the preferential binding region for both proteins. Computational results supported these findings, showing high affinity for DS1, with binding energies of −69.02 kcal·mol⁻¹ (HSA) and −67.22 kcal·mol⁻¹ (BSA). While complex formation was confirmed for both proteins, differences emerged in the induced circular dichroism (ICD) signals. HSA displayed a distinct ICD profile compared to BSA in both intensity and absorption maximum. Molecular Docking revealed that the C343 conformation differed between HSA and BSA, explaining the variation in ICD signals. These results highlight the importance of protein structure in modulating ligand interactions and spectral responses. Full article