Search Results (76)

The microtubule-associated protein tau, encoded by the MAPT gene, serves as a major component of the neuronal cytoskeleton, facilitating the assembly, stabilization, and spatial organization of microtubules. Much of the work on tau has focused on the low-molecular-weight (LMW) isoforms abundantly expressed in the central nervous system (CNS) and their pathological aggregation in tauopathies. However, a different variant known as “Big tau”, present in the peripheral nervous system (PNS) and selective CNS regions has distinct structural and functional properties and offers a unique perspective on protein evolution. Big tau is characterized by the inclusion of a large, alternatively spliced insert termed exon 4a, which expands the protein’s projection domain by approximately 250 amino acids and increases the molecular weight to 90–110 kDa. The evolutionary trajectory of exon 4a presents a fascinating enigma that challenges conventional models of protein conservation. Across the vertebrate phylogeny, spanning from fishes, amphibians and birds to mammals, the primary amino acid sequence of exon 4a exhibits extreme divergence, often reaching background levels of identity when comparing distant classes. In contrast, the physical length of this domain remains remarkably stable, hovering around the 250-amino acid mark regardless of the species. This pattern suggests that the selective pressure acting on Big tau is not directed toward specific sequence motifs or functional domains, but rather toward the biophysical properties and physical dimensions of the domain. Here, we posit that exon 4a evolved as an essential molecular spacer optimized for the structural demands of long-projection neurons and high-caliber axons as well as a protective structure for the pathologic aggregation of tau. The paper examines the genomic architecture and biophysical identity underlying the stable-size and low sequence identity of exon 4a, presenting two evolutionary mechanisms as working hypotheses: a Prototype Model of neutral drift of an ancient insert, and an Independent Exonization of convergent recruitment of non-coding DNA by transposable elements or intron retention. Finally, we emphasize the need for additional experimental work in vitro and in vivo to resolve unanswered questions about the structure of the 4a exon, the physiological role Big tau and its potential insight into tauopathies therapeutics. Full article

Solanum elaeagnifolium has been utilized for its analgesic, anti-inflammatory, and antioxidant properties to treat a range of conditions, including pain and inflammation. It possesses antibacterial, insecticidal, and molluscicidal properties as well. To investigate the pharmacological potential of the S. elaeagnifolium extract, in vitro, in vivo, and in silico studies were used. Albumin denaturation, heat-induced anti-haemolytic action, and lipooxygenase inhibition were the three techniques used to test anti-inflammatory effectiveness. The phenolic chemicals utilized were identified through the use of high-performance liquid chromatography (HPLC). The effectiveness of the extract in lowering problems connected to diabetes was further evaluated by evaluating fructosamines, carbonyl groups, and β-amyloid formations in albumin glycation. Regarding in vivo studies, the Writhing test and the tail flick test were the two techniques used to evaluate analgesic activity. For docking analysis, we used the following identifiers: cyclooxygenase (PDB ID: 6COX), lipooxygenase (PDB ID: 3V99) and VC1 domain of the receptor for advanced glycation products (PDB ID: 7LMW). The most prevalent phenolic chemicals, according to HPLC analysis, were 3,4-dihydroxybenzoic acid (4.78%), caffeic acid (1.28%), gallic acid (8.18%), ursolic acid (2.6%), syringic acid (1.78%), quercetin (24.09%), catechin (6.67%), and p-coumaric acid (20.49%). Significant suppression of albumin glycation and fructosamine production was demonstrated by the extract, indicating that it may help lessen difficulties associated with diabetes. Furthermore, the extract demonstrated a strong anti-inflammatory impact, with an IC₅₀ of 146 ± 1.17 μg/mL for lipooxygenase inhibition, 87.64 ± 5.35 μg/mL for anti-haemolytic action, and 86.94 ± 1.63 μg/mL for albumin denaturation inhibition. A similar analgesic effect to those of analgesic medications was also demonstrated by SEFE extract. Reinforcing the relevance of the observed effects, the in silico study of the tested activities validated these findings. These findings indicate significant pharmacological promise in the management of diabetes consequences, including inflammation and protein glycation, as well as an analgesic. Full article

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), represents a major global health challenge, driven by the increasing prevalence of obesity and sedentary lifestyles. T2DM is characterized by insulin resistance and progressive β-cell dysfunction, leading to chronic hyperglycemia and multiple complications. Among the molecular targets investigated for therapeutic intervention, protein tyrosine phosphatase 1B (PTP1B) has emerged as a key negative regulator of insulin signaling. By dephosphorylating the insulin receptor and its downstream substrates, PTP1B attenuates insulin action and contributes to metabolic dysfunction. In addition to its role in glucose homeostasis, PTP1B is implicated in obesity, diabetic complications, neurodegenerative disorders, and cancer, highlighting its relevance as a multifunctional therapeutic target. However, the development of PTP1B inhibitors remains challenging due to the highly conserved and polar nature of its catalytic site, which limits selectivity and cell permeability. Recent research has focused on alternative strategies, including allosteric modulation and multi-site inhibition, to overcome these limitations. This review provides a comprehensive overview of PTP1B inhibitors from both synthetic (2019–2025) and natural sources, with particular emphasis on natural products reported from 2022 onwards, while including selected earlier studies to provide historical context and illustrate representative structural classes and inhibition mechanisms. Although PTP1B remains an attractive therapeutic target, its clinical validation for diabetes treatment has yet to be achieved. Continued advances in medicinal chemistry and allosteric modulation may help overcome the current translational barriers. Full article

Ferulic acid (FA) is a phenolic acid mainly present in wheat bran. It has beneficial health effects, but may affect gluten network formation and the processing quality of wheat-based products. This study investigated the interaction mechanisms between FA and glutenin/gliadin in dough and simulated dough systems. The results show that FA’s effects on both proteins were dose and system dependent. In dough, low-dose FA (≤0.3 g) promoted structural loosening of glutenin, as suggested by β-sheet conversion to β-turns/random coil structures, increased t-g-t disulfide and free thiols, and reduced particle size, whereas high doses promoted reaggregation via microenvironment reshaping, hydrophobic enhancement, cross-linking, and subunit rearrangement. For gliadin, low-dose FA may have altered local charge and hydrogen-bonding environments, while high-dose FA increased the hydrogen-bonding proportion by 45.71% and g-g-g conformation by 60.85%, suggesting enhanced molecular aggregation. In simulated dough, FA promoted stronger structural loosening of glutenin but favored gliadin aggregation, indicating that starch, lipids, water distribution, and other dough components may redirect FA–protein interactions. Molecular docking, as a complementary approach, predicted the preferential binding of FA to gliadin, LMW-GS and HMW-GS at different sites. These findings provide a theoretical basis for regulating phenolic acid–gluten interactions in whole-wheat and functional wheat-based products. Full article

Background: Postbiotics, including cell-free supernatants and their fractions, have emerged as a safe and effective alternative to live probiotics for managing intestinal inflammation. This study investigated the protective effects of low-molecular-weight fractions (<3 kDa) of the probiotic Limosilactobacillus fermentum CECT5716 (LMW-LF) in a murine model of experimental colitis. Methods: Male C57BL/6J mice were orally administered LMW-LF for 10 days prior to colitis induction with 3% dextran sodium sulfate (DSS) for 5 days. Colonic damage was assessed via the Disease Activity Index (DAI), histology, and immunofluorescence (Ocln and Ki67). Immune cell populations were analyzed by flow cytometry, while mucosal gene expression and gut microbiota composition were evaluated using RT-qPCR and 16S rRNA sequencing, respectively. Results: LMW-LF administration significantly attenuated clinical symptoms and macroscopic colonic damage. Treatment restored epithelial barrier integrity by upregulating tight junction proteins (Tjp1) and mucin genes (Muc1-3) while normalizing DSS-induced epithelial hyperproliferation. Immunologically, LMW-LF reduced pro-inflammatory monocyte infiltration; downregulated Il6, Tnfa, and Ifng; and promoted an immunoregulatory phenotype by enhancing Ampk expression and partially restoring regulatory T cell (Treg) populations. Furthermore, LMW-LF reshaped the gut microbiota by increasing alpha diversity and promoting the enrichment of beneficial taxa, specifically Akkermansia muciniphila, which correlated with improved mucus layer preservation. Conclusions: LMW-LF is an active fraction acting across the host–microbiota axis. By integrating epithelial protection, immunomodulation, and microbial reshaping, it represents a promising dietary strategy for the management of Inflammatory Bowel Diseases. Full article

Salt stress is a critical abiotic constraint affecting wheat yield and quality. In this study, we employed pot experiments under controlled salinity (2.8‰ NaCl) and multi-omics approaches to elucidate the regulatory mechanisms underlying grain quality formation in a strong-gluten wheat variety, Jinan 17. Key findings revealed that salt stress caused a significant 41.27% reduction in 1000-kernel weight, while protein content increased by 13.82%. However, bread volume and bread score were reduced by 16.85% and 13.08%, respectively. Multi-omics integration uncovered that salt stress repressed the expression of starch synthesis-related genes (e.g., TraesCS2A03G0349200), diverting carbon skeletons toward amino acid metabolism pathways. This metabolic reprogramming disrupted the glutenin/gliadin ratio (down 14.35%), with high molecular weight glutenin subunits (HMW-GS) synthesis being suppressed, while low molecular weight glutenin subunits (LMW-GS) and gliadin accumulated by 19.28% and 24.76%, respectively, forming a “high extensibility but low elasticity” gluten network. Furthermore, transcriptomic analysis identified significant upregulation of arginine metabolism genes (e.g., TraesCS6A03G0029900), which enhanced osmolyte biosynthesis and exacerbated carbon–nitrogen partitioning imbalances. This study provides novel insights into the molecular mechanisms of flour quality deterioration under saline conditions and identifies critical regulatory nodes for simultaneous improvement of starch synthesis and gluten network architecture in salt-affected wheat breeding programs. Full article

Wheat end-product quality results from complex interactions among protein, starch, and fiber, further complicated by genetic and environmental variability, especially in commercial samples composed of multiple varieties from diverse regions. Eighteen composite samples of hard red spring wheat (HRSW) were prepared from 755 field samples to simulate commercial grain blending. These composites were analyzed to evaluate the influence of flour composition on product quality. A wide range of flour compositional properties was analyzed and associated with dough and end-product quality traits, as measured by GlutoPeak, Rapid Visco Analyzer, Farinograph, Extensograph, Alveograph, and loaf baking. The results indicated that dough and bread quality are not determined by protein or gluten content alone, but that protein, starch and fiber composition and structural variations play a crucial role. Flours with higher proportions of high-molecular-weight glutenin (HMW-GS) fractions, particularly those rich in Bx and Ax subunits, exhibited greater dough resistance, mixing strength, and bread volume. In contrast, lower-performing samples were characterized by reduced HMW/LMW, polymeric/monomeric protein ratios, and HMW-Bx content. Multivariate modeling showed strong predictive performance for loaf volume (R² > 0.860) when protein, starch and fiber quality metrics were combined with protein content. These findings provide a data-driven framework for wheat flour classification and optimizing processing formulation. Full article

Wheat allergy (WA) poses a diagnostic challenge due to its diverse clinical phenotypes—ranging from classic food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA) to baker’s asthma. An additional diagnostic aspect is serological cross-reactivity with grass pollen. Undoubtedly, the transition from extract-based diagnostics to precise component-based diagnostics (CRDs) facilitates the management of wheat allergy. It has significantly improved the diagnostic accuracy for WDEIA ω-5-gliadin (Tri a 19), although considering new knowledge about wheat proteins, it seems necessary to include them in the diagnostic scheme, especially where Tri a 19 remains negative despite clinical symptoms. Therefore, in this review, we evaluate the clinical utility of new wheat molecules with a high risk of anaphylaxis. We pay particular attention to Tri a 37 (α-purothionin), a thermally stable allergen associated with a 4-fold increase in the risk of severe anaphylaxis, and Tri a 36 (LMW glutenin), which shows higher sensitivity than Tri a 19 in specific pediatric cohorts. In addition, we emphasize the role of Tri a 14 (nsLTP) in distinguishing true wheat sensitization from pollen-related cross-reactivity caused by profilins (Tri a 12) or carbohydrate determinants (CCDs). Beyond diagnostics, the review discusses dynamic changes in sensitization profiles in relation to the allergic march and the phenomenon of spontaneous remission in children. New management strategies are also discussed, including the potential of omalizumab (based on the data from the OUtMATCH study) in facilitating the reintroduction of allergens into the diet. Full article

The increasing demand for advanced cosmetic formulations based on natural biopolymers has stimulated the design of multifunctional and sustainable skin care products. Hyaluronic acid (HA) and silk proteins are widely recognized for their hydrating, barrier-supportive, and biocompatible properties. This study aimed to develop a novel topical formulation, integrating low- and medium molecular weight hyaluronic acid (LMW-HA and MMW-HA), encapsulated sodium hyaluronate (NaHA), silk, and hydrolyzed silk as active components, aiming to enhance skin barrier function and biocompatibility. The formulation was subjected to comprehensive physicochemical characterization including evaluation of appearance, odor, color, pH, viscosity, and stability, all assessed over 30 days and microbiological stability testing under controlled storage conditions. Safety evaluation followed a dual-phase strategy: (i) in silico toxicological screening of individual ingredients, including sensitization, and mutagenicity predictions, and (ii) in vivo skin compatibility assessment in 25 human volunteers using a semi-occlusive patch test. The formulation demonstrated good physicochemical stability, as pH remained stable, and viscosity showed no significant changes, confirming structural integrity, indicating preserved structural and microbiological stability throughout the study period. The in silico assessment indicated no mutagenic and/or sensitizing alerts and favorable safety margins for all components, confirming the safety profile of each ingredient, supporting their suitability for dermocosmetic use, while in vivo evaluation revealed no significant adverse effects, with irritation scores indicating no skin reaction (erythema or edema) across the test population. These findings support the potential of this novel biopolymer-based formulation as a safe and well-tolerated dermocosmetic product, aligning with principles of sustainable development and biomimetic design. Full article

Low Molecular Weight Glutenin Subunits (LMW-GS) proteins have great effects on the end-use quality of bread wheat and are difficult to differentiate directly. It is very important to characterize and classify LMW-GS genes systematically. In this paper, 692 complete Glu-3 gene sequences were retrieved from GenBank and were grouped based on their sequence characters and variations. Based on the characters of their N-terminal sequences, these genes were classified into two types, LMW-m and LMW-i, of which LMW-m genes were further classified into three sub-types based on their first amino acid (AA) (LMW-M, LMW-V and LMW-I). Based on the first seven or eight AA variations in the N-terminal sequence, LMW-GS Glu-3 genes were classified into 16 types, namely LMW-N1 to LMW-N16. Based on the last 10 AA variations in the C-terminal, the Glu-3 genes were classified into 22 types, designated as LMW-C1 to LMW-C22. Based on the number and distribution of cysteines, the Glu-3 genes classified into 22 types included 7 conventional types with eight cysteines and 15 variant types with seven or nine cysteines. In addition, two new Glu-A3 genes (GluA-10 and GluA-11) were identified based on their sequence homology, and the connection between different classification methods was analyzed briefly. The results provide insight into the nature of the Glu-3 gene family and are valuable for molecular marker-assisted selection of end-use quality traits in wheat improvement. Full article

Wheat is a crucial crop for human nutrition, and the demand for high-quality indicators within the “from farm to fork” concept is increasing. Based on this premise, this study examined how, at the farm level, the fertilization system can influence key quality indicators relevant to wheat production and final products. This research was conducted under specific conditions of the Western Plain of Romania at the Agricultural Research and Development Station (ARDS), Lovrin, during 2015–2017. Fertilization involved the autumn application of phosphorus (concentrated superphosphate; 0, 40, 80, 120, 160 kg ha⁻¹ active substance, a.s.) and potassium (potassium chloride; 0, 40, 80, 120 kg ha⁻¹ a.s.). Nitrogen (ammonium nitrate; 0, 30, 60, 90, 120 kg ha⁻¹ active substance) was applied in spring in two stages. The combination of these three fertilizers resulted in 18 fertilized variants (T2 to T19), tested alongside an unfertilized control (T1). The experimental variants were arranged in four randomized replications. Grain quality was assessed based on protein content (PRO, %), gluten (GLT, g 100 g⁻¹), gliadins (Gliad, %), glutenins (Glut, g 100 g⁻¹), high-molecular-weight glutenins (HMW, g 100 g⁻¹), low-molecular-weight glutenins (LMW, g 100 g⁻¹), and the gliadin/glutenin ratio (Gliad/Glut). Compared to the average values for each indicator across the experiment, certain variants produced values above the mean, with statistical significance. Variant T16 stood out by producing values above the mean for all indicators, with statistical confidence. Multivariate analysis showed that five indicators with very strong (PRO, GLT) and strong (HMW, Glut, LMW) influence grouped in PC1, while two indicators (Gliad, Gliad/Glut) with very strong and strong influence grouped in PC2. The analysis revealed varying levels of correlation between the applied fertilizers, with nitrogen (N) showing very strong and strong correlations with most indicators, while phosphorus and potassium showed moderate-to-weak correlations. Regression analysis generated mathematical models that statistically described how each indicator varied in relation to the fertilizers applied. Full article

Most lacustrine dissolved organic matter (DOM) still lacks comprehensive environmental sources and molecular characterization, especially in plateau lakes. Herein, macrophytes and algae from contrasting lakes of the Yunnan-Guizhou Plateau, together with Suwannee River fulvic acid (SRFA), were used to characterize the total identified DOM (Bulk-DOM) and low-molecular-weight DOM (LMW-DOM, <200 Da). To address this, we combined spectroscopy with Fourier transform ion cyclotron resonance (FT-ICR) and Orbitrap mass spectrometry (MS). Algae-derived DOM (ADOM) exhibited endogenous DOM characteristics, while macrophyte-derived DOM (MDOM) showed the characteristics of endogenous and terrigenous DOM. ADOM contained numerous heteroatoms, with high proportions of proteins, carbohydrates, and lipids. The chemical structures of ADOM were more aliphatic and degradable than that of MDOM. Conversely, MDOM and SRFA had higher degree of humification and aromaticity and showed greater resistance to microbial degradation. The capability of Orbitrap MS to characterize P-containing molecules was superior to FT-ICR MS. Moreover, significant differences were found between FT-ICR and Orbitrap MS in weighted average carbon atom number, weighted average mass-to-charge ratio, carbohydrates, and P-containing compounds. LMW-DOM accounted for approximately 10% of Bulk-DOM. Compared to Bulk-DOM, LMW-DOM was more active than Bulk-DOM because of the reduced state and more N-containing compounds. This study provides a valuable perspective to reveal the molecular characteristics and behaviors of ADOM and MDOM, which has crucial implications for carbon cycling in aquatic ecosystems. Full article

Objectives: The compound 3-(4-Hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a terminal metabolite derived from polyphenol compounds. It has been studied for its potential to support brain health indirectly through its anti-oxidant effects and ability to enhance the gut environment; however, its role in dementia pathogenesis is unclear. Therefore, the aim of this study was to evaluate how HMPA inhibits Aβ42 aggregation in vitro. Methods: We examined the inhibitory effects of HMPA on amyloid-β protein (Aβ) aggregation using a thioflavin T (ThT) assay and electron microscopy (EM). Results: ThT assays demonstrated that HMPA inhibited both the nucleation and elongation phases of Aβ aggregation. Additionally, EM of low-molecular-weight (LMW) Aβ42 in the presence of HMPA demonstrated shorter fibrils compared to those formed without HMPA. The EC₅₀ of HMPA in LMW Aβ42 was 5–6 mM. Conclusions: These findings indicate that, similar to several polyphenol compounds such as myricetin and rosmarinic acid, HMPA may inhibit Aβ pathogenesis, although it requires a fairly high concentration in vitro. These findings suggest the potential of HMPA as a lead compound for modulating Aβ-related neurodegeneration. Full article

With climate change, maintaining wheat quality has become essential for the functional properties, end-use, commodity value, and nutritional benefits of wheat flour. Temperature indirectly influences wheat quality by modulating grain size, starch and protein content, and the balance between these components. This review systematically analyzes temperature-mediated alterations in wheat grain quality, with particular emphasis on the two core components: starch and protein. Specifically, daytime warming generally increases protein content while reducing starch accumulation; however, temperatures exceeding 30 °C diminish key protein quality parameters (UPP%, Glu/Gli ratio, HMW-GS/LMW-GS ratio). Nighttime warming enhances protein quality but compromises starch content and yield potential. Conversely, under low-temperature conditions, starch content declines, whereas protein content is primarily influenced by genotypes and treated temperatures. Furthermore, the underlying mechanisms driving temperature-induced changes in wheat quality traits are discussed. However, the mechanisms of temperature effects have not been fully elucidated, and the results often vary between regions or over years. Thus, identifying conserved high/low-temperature resistance genes, QTLs, epialleles, and epiQTL, as well as developing corresponding molecular markers and epi-markers, is an urgent priority. Meanwhile, genome-editing tools such as CRISPR/Cas could serve as a powerful approach for creating new wheat germplasm with durable high/low-temperature resistance. Full article

Low molecular weight glutenin subunits (LMW-GSs) in wheat are critical functional proteins that regulate the processing quality of flour-based products. This study utilized two sets of near-isogenic lines (NILs) derived from the wheat cultivars Zhoumai 22 and Zhoumai 23 to investigate the effects of allelic variations at the Glu-A3 locus—specifically Glu-A3a, Glu-A3b, Glu-A3c, Glu-A3d, Glu-A3e, Glu-A3f, and Glu-A3g—on protein content, gluten properties, dough farinograph properties, cooking properties of fresh wet noodles (FWNs), and textural properties of FWNs and frozen cooked noodles (FZNs). The results demonstrated that Glu-A3f exhibited superior grain protein content. Glu-A3e negatively impacted the gluten index, and Glu-A3g showed favorable dry gluten content. Glu-A3b displayed enhanced dough mixing tolerance. Importantly, Glu-A3b was associated with improved hardness in FWNs, while Glu-A3g contributed to higher hardness and chewiness in FZNs. These findings provide critical insights for breeding elite wheat cultivars tailored for noodle production and optimizing specialty flour development. Full article