Search Results (19,188)

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis. Full article

Pleurotus eryngii is an edible mushroom with previously characterized β-glucans. Its potential to ameliorate postprandial glycemia and regulate appetite at the postprandial state has been previously shown. However, its effect on protein digestion remains unexplored. We aimed to investigate the effect of baked P. eryngii with a known β-glucan content (4.5 g) on plasma free amino acids of patients with central obesity and metabolic abnormalities at a postprandial state. In this acute, randomized controlled cross-over study, thirteen healthy male volunteers consumed one meal that was prepared with P. eryngii and one control meal; each meal was separated by one month. Blood was collected, and plasma was isolated at different timepoints before and after the consumption. Gas chromatography–mass spectrometry was used to quantify 24 free amino acids in the plasma samples. The area under the curve with respect to increase (AUCi) was computed, and the AUCi for aromatic amino acids was found to be higher after the consumption of the control meal compared to the P. eryngii meal (p = 0.027 for phenylalanine, p = 0.008 for tyrosine, and p = 0.003 for tryptophan). The above novel findings suggest that the β-glucans present in P. eryngii mushrooms are potential modulators of AA release into the bloodstream. Full article

The food industry consumes large amounts of water across various processes, and generates wastewater characterized by parameters like biochemical oxygen demand, chemical oxygen demand, pH, suspended solids, and nutrients. To meet environmental standards and enable reuse or valorization, treatment methods such as physicochemical, biological, and membrane-based processes are applied. This review focuses on the valorization of food industry wastewater in the biotechnological production of high-value products, with an emphasis on starch-rich wastewater, wineries and confectionery industry wastewater, and with a focus on new technologies for reduces environmental burden but also supports circular economy principles. Starch-rich wastewaters, particularly those generated by the potato processing industry, offer considerable potential for biotechnological valorization due to their high content of soluble starch, proteins, organic acids, minerals, and lipids. These effluents can be efficiently converted by various fungi (e.g., Aspergillus, Trichoderma) and yeasts (e.g., Rhodotorula, Candida) into value-added products such as lipids for biodiesel, organic acids, microbial proteins, carotenoids, and biofungicides. Similarly, winery wastewaters, characterized by elevated concentrations of sugars and polyphenols, have been successfully utilized as medium for microbial cultivation and product synthesis. Microorganisms belonging to the genera Aspergillus, Trichoderma, Chlorella, Klebsiella, and Xanthomonas have demonstrated the ability to transform these effluents into biofuels, microbial biomass, biopolymers, and proteins, contributing to sustainable bioprocess development. Additionally, wastewater from the confectionery industry, rich in sugars, proteins, and lipids, serves as a favorable fermentation medium for the production of xanthan gum, bioethanol, biopesticides, and bioplastics (e.g., PHA and PHB). Microorganisms of the genera Xanthomonas, Bacillus, Zymomonas, and Cupriavidus are commonly employed in these processes. Although there are still certain regulatory issues, research gaps, and the need for more detailed economic analysis and kinetics of such production, we can conclude that this type of biotechnological production on waste streams has great potential, contributing to environmental sustainability and advancing the principles of the circular economy. Full article

Background: Protein kinase R (PKR) inhibits general mRNA translation by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF2). PKR also modulates NF-κB signaling during viral infections, but comparative studies of PKR-mediated NF-κB responses across mammalian species and their regulation by viral inhibitors remain largely unexplored. This study aimed to characterize the conserved antiviral and inflammatory roles of mammalian PKR orthologs and investigate their modulation by poxviral inhibitors. Methods: Using reporter gene assays and quantitative RT-PCR, we assessed the impact of 17 mammalian PKR orthologs on general translation inhibition, stress-responsive translation, and NF-κB-dependent induction of target genes. Congenic human and rabbit cell lines infected with a myxoma virus strain lacking PKR inhibitors were used to compare the effects of human and rabbit PKR on viral replication and inflammatory responses. Site-directed mutagenesis was employed to determine key residues responsible for differential sensitivity to the viral inhibitor M156. Results: All 17 mammalian PKR orthologs significantly inhibited general translation, strongly activated stress-responsive ATF4 translation, and robustly induced NF-κB target genes. Inhibition of these responses was specifically mediated by poxviral K3 orthologs that effectively suppressed PKR activation. Comparative analyses showed human and rabbit PKRs similarly inhibited virus replication and induced cytokine transcripts. Amino acid swaps between rabbit PKRs reversed their sensitivity to viral inhibitor M156 and NF-κB activation. Conclusions: Our data show that the tested PKR orthologs exhibit conserved dual antiviral and inflammatory regulatory roles, which can be antagonized by poxviral K3 orthologs that exploit eIF2α mimicry to modulate the PKR-NF-κB axis. Full article

Psoriasis is a chronic inflammatory skin disorder involving oxidative stress and immune dysregulation. Given the limitations and adverse effects of conventional therapies, interest in natural treatments with anti-oxidant and immunomodulatory properties is increasing. This study aimed to comprehensively evaluate the therapeutic potential of Galium verum extract in an imiquimod-induced rat model of psoriasis. The extract was chemically characterized by HPLC and evaluated for anti-oxidant activity using DPPH, ABTS, and FRAP assays. Molecular docking studies targeted psoriasis-related proteins (IL-17, IL-22, IL-23, JAK2, MAPK2, NF-κB, STAT3), revealing strong binding affinities for rutin and quercetin, the extract’s dominant bioactives. In vivo, 18 Wistar albino male rats were divided into control (CTRL), psoriasis (PSORI), and psoriasis treated with Galium verum (PSORI + GV) groups. A seven-day topical application of 5% imiquimod cream was used for the induction of psoriasis. The PSORI + GV group received 250 mg/kg Galium verum extract orally for 7 days. Morphometric and redox analyses were performed. Histological and morphometric analyses showed reduced epidermal thickness, inflammation, and collagen content. Redox analysis revealed lowered oxidative stress biomarkers and enhanced anti-oxidant defenses. These findings suggest that Galium verum extract exerts anti-psoriatic effects through antioxidative and immunomodulatory mechanisms, supporting its potential as a natural adjunct therapy for psoriasis. Full article

Segregative phase separation technology demonstrates substantial potential for precise molecular fractionation in food and biomaterial applications. The investigation elucidates the causal relationship between viscosity variations and phase separation dynamics, which govern molecular fractionation in GA/HPMC composite systems. By conducting a comparative analysis of two GA subtypes (CGA and SGA) and three HPMC grades with controlled viscosity gradients, we utilized gel permeation chromatography-multi-angle laser light scattering (GPC-MALLS) coupled with rheological characterization to elucidate the critical relationship between continuous phase viscosity and fractionation efficiency. Notably, increasing HPMC viscosity significantly intensified phase separation, resulting in selective enrichment of arabinogalactan-protein complexes: from 6.3% to 8.5% in CGA/HPMC systems and from 27.3% to 36.5% in SGA/HPMC systems. Further mechanistic investigation revealed that elevated HPMC viscosity enhances thermodynamic incompatibility while slowing interfacial mass transfer, synergistically driving component redistribution. These findings establish a quantitative viscosity–fractionation relationship, offering theoretical insights for optimizing GA/HPMC systems in emulsion stabilization, microencapsulation, and functional biopolymer purification via viscosity-mediated phase engineering. Full article

Nucleocytoplasmic trafficking is a highly regulated process that allows the cell to control the partitioning of proteins and nucleic acids between the cytosolic and nuclear compartments. The Ebola virus minor matrix protein VP24 (eVP24) hijacks this process by binding to a region on the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear importers. This region overlaps with the activated transcription factor STAT1 binding site on KPNAs, preventing STAT1 nuclear localization and activation of antiviral gene transcription. However, the molecular interactions of eVP24-KPNA5 binding that lead to the nuclear localization of eVP24 remain poorly characterized. Here, we show that trafficking of eVP24 into the nucleus by KPNA5 requires simultaneous binding of cargo. We also describe the conformational dynamics of KPNA5 and interactions with eVP24 and cargo nuclear localization sequences (NLS) using biophysical approaches. Our results reveal that eVP24 binding to KPNA5 does not impact cargo NLS binding to KPNA5, indicating that simultaneous binding of both cellular cargo and eVP24 to KPNA5 is likely required for nuclear trafficking. Together, these results provide a biophysical basis for how Ebola virus VP24 protein gains access to the nucleus during Ebola virus infection. Full article

Background/Objectives: Diatomaceous earth (DE), a natural substance rich in amorphous silica and recognized as a food additive, is gaining attention as a dietary silicon supplement. However, its bioavailability and impact on lipid digestion and absorption remain poorly characterized. This study aimed to investigate silicon bioavailability after short-term DE supplementation and its effects on postprandial glycemia and triglyceridemia, the expression of lipid metabolism-related proteins, and the modulation of the intestinal mucosal barrier. Methods: Female Wistar rats received daily oral supplementation of DE (equivalent to 2 or 4 mg silicon/kg body weight) for one week. Silicon digestibility, excretion, and hepatic accumulation were quantified. Postprandial glycemia and triglyceridemia were monitored. Lipid profile was analyzed by HPSEC in gastric and intestinal contents. Jejunal morphology and mucin-secreting cells were assessed histologically. Lipid metabolism markers were evaluated by immunohistochemistry and Western blot in both intestinal and hepatic tissues. Results: DE supplementation enhanced silicon absorption and increased hepatic levels. Fecal output and moisture content were also elevated, especially at the higher dose. DE significantly reduced postprandial triglyceridemia and consequently increased luminal triglyceride retention. These changes were associated with decreased jejunal levels of IFABP, ACAT2, and MTP, as well as reduced hepatic levels of MTP and LDLr, alongside increased levels of ABCG5/G8 and LXRα/β, indicating a partial blockage of lipid absorption and enhanced cholesterol efflux. The effects on the intestinal barrier were evidenced by villi shortening and an increase in mucin-producing cells. Conclusion: Food-grade DE is a bioavailable source of silicon with hypolipidemic potential, mainly by reducing intestinal lipid absorption. This is supported by lower postprandial triglycerides, increased luminal lipid retention, and decreased expression of lipid transport proteins. The study in healthy female rats underscores the importance of sex-specific responses and supports DE as a dietary strategy to improve lipid metabolism. Full article

Background: Pepper (Capsicum annuum L.) is highly susceptible to various abiotic stresses during their growth and development, leading to severe reductions in both yield and quality. β-Glucosidase (BGLU) is widely involved in plant growth and development, as well as in the response to abiotic stress. Methods: We performed a genome-wide identification of pepper BGLU (CaBGLU) genes. Phylogenetic analysis included BGLU proteins from Arabidopsis, tomato, and pepper. Gene structures, conserved motifs, and promoter cis-elements were analyzed bioinformatically. Synteny within the pepper genome was assessed. Protein-protein interaction potential was predicted. Gene expression patterns were analyzed across tissues and under abiotic stresses using transcriptomic data and qRT-PCR. Subcellular localization of a key candidate protein CaBGLU21 was confirmed experimentally. Results: We identified 32 CaBGLU genes unevenly distributed across eight chromosomes. Phylogenetic classification of 99 BGLU proteins into 12 subfamilies revealed an uneven distribution of CaBGLUs across six subfamilies. Proteins within subfamilies shared conserved motifs and gene structures. CaBGLU promoters harbored abundant light-, hormone- (MeJA, ABA, SA, GA), and stress-responsive elements (including low temperature). A duplicated gene pair (CaBGLU19/CaBGLU24) was identified. 27 CaBGLU proteins showed potential for interactions. Expression analysis indicated CaBGLU5 and CaBGLU30 were mesophyll-specific, while CaBGLU21 was constitutively high in non-leaf tissues. CaBGLU21 was consistently upregulated by cold, heat, and ABA. Subcellular localization confirmed CaBGLU21 resides in the tonoplast. Conclusions: This comprehensive analysis characterizes the pepper BGLU gene family. CaBGLU21, exhibiting constitutive expression in non-leaf tissues, strong upregulation under multiple stresses, and tonoplast localization, emerges as a prime candidate gene for further investigation into abiotic stress tolerance mechanisms in pepper. The findings provide a foundation for future functional studies and stress-resistant pepper breeding. Full article

We conducted systematic glycomic and glycoproteomic profiling to characterize the dynamic N-glycosylation landscape of rat serum, with particular focus on sex- and time-dependent variations. MALDI-TOF-MS analysis revealed that rat serum N-glycans are predominantly biantennary, disialylated complex-type structures with extensive O-acetylation of Neu5Ac residues, especially in females. LC-MS/MS-based glycoproteomic analysis of albumin/IgG-depleted serum identified 87 glycoproteins enriched in protease inhibitors (e.g., serine protease inhibitor A3K) and immune-related proteins such as complement C3. Temporal analyses revealed stable sialylation in males but pronounced daily fluctuations in females, suggesting hormonal influence. Neu5Gc-containing glycans were rare and mainly derived from residual IgG, as confirmed by glycomic analysis. In contrast to liver-derived glycoproteins, purified IgG exhibited Neu5Gc-only sialylation without O-acetylation, underscoring distinct sialylation profiles characteristic of B cell-derived glycoproteins. Region-specific glycosylation patterns were observed in IgG, with the Fab region carrying more disialylated structures than Fc. These findings highlight cell-type and sex-specific differences in sialylation patterns between hepatic and immune tissues, with implications for hormonal regulation and biomarker research. This study provides a valuable dataset on rat serum glycoproteins and underscores the distinctive glycosylation features of rats, reinforcing their utility as model organisms in glycobiology and disease research. Full article

Background: During food processing and storage, traditional protein-based delivery systems encounter significant challenges in maintaining the structural and functional integrity of bioactive compounds, primarily due to their temporal instability. Methods: In this study, a nanocomposite hydrogel was prepared through the co-assembly of a self-assembling peptide, 9-Fluorenylmethoxycarbonyl-phenylalanine-arginine-glycine-aspartic acid-phenylalanine (Fmoc-FRGDF), and hyaluronic acid (HA). The stability of this hydrogel as a quercetin (Que) delivery carrier was systematically investigated. Furthermore, the impact of Que co-assembly on the microstructural evolution and physicochemical properties of the hydrogel was characterized. Concurrently, the encapsulation efficiency (EE%) and controlled release kinetics of Que were quantitatively evaluated. Results: The findings indicated that HA significantly reduced the storage modulus (G′) from 256.5 Pa for Fmoc-FRGDF to 21.1 Pa with the addition of 0.1 mg/mL HA. Despite this reduction, HA effectively slowed degradation rates; specifically, residue rates of 5.5% were observed for Fmoc-FRGDF alone compared to 14.1% with 0.5 mg/mL HA present. Notably, Que enhanced G′ within the ternary complex, increasing it from 256.5 Pa in Fmoc-FRGDF to an impressive 7527.0 Pa in the Que/HA/Fmoc-FRGDF hydrogel containing 0.1 mg/mL HA. The interactions among Que, HA, and Fmoc-FRGDF involved hydrogen bonding, electrostatic forces, and hydrophobic interactions; furthermore, the co-assembly process strengthened the β-sheet structure while significantly promoting supramolecular ordering. Interestingly, the release profile of Que adhered to the Korsmeyer–Peppas pharmacokinetic equations. Conclusions: Overall, this study examines the impact of polyphenol on the rheological properties, microstructural features, secondary structure conformation, and supramolecular ordering within peptide–polysaccharide–polyphenol ternary complexes, and the Fmoc-FRGDF/HA hydrogel system demonstrates a superior performance as a delivery vehicle for maintaining quercetin’s bioactivity, thereby establishing a multifunctional platform for bioactive agent encapsulation and controlled release. Full article

Protein degradation plays a fundamental role in maintaining protein homeostasis and ensures proper cellular function by regulating protein quality and quantity. Heat shock protein 100 (Hsp100), found in bacteria, plants, and fungi, is a unique chaperone family responsible for rescuing misfolded proteins from aggregated states in an ATP-dependent manner. To date, they are primarily known to mediate heat stress adaptation and enhance cellular survival under extreme conditions in higher plants and algae. Resting cyst formation in dinoflagellates is widely recognized as a response to adverse conditions, which offers an adaptive advantage to endure harsh environmental extremes that are unsuitable for vegetative cell growth and survival. In this study, based on a full-length cDNA sequence, we characterized an Hsp100 gene (SaHsp100) from the cosmopolitan bloom-forming dinoflagellate Scrippsiella acuminata, aiming to examine its life stage-specific expression patterns and preliminarily explore its potential functions. The qPCR results revealed that Hsp100 transcript levels were significantly elevated in newly formed resting cysts compared to vegetative cells and continued to increase during storage under simulated marine sediment conditions (darkness, low temperature, and anoxia). Parallel reaction monitoring (PRM)-based quantification further confirmed that Hsp100 protein levels were significantly higher in resting cysts than in vegetative cells and increased after three months of storage. These findings collectively highlighted the fundamental role of Hsp100 in the alteration of the life cycle and dormancy maintenance of S. acuminata, likely by enhancing stress adaptation and promoting cell survival through participation in proteostasis maintenance, particularly under natural sediment-like conditions that trigger severe abiotic stress. Our work deepens the current understanding of Hsp family members in dinoflagellates, paving the way for future investigations into their ecological relevance within this ecologically significant group. Full article

Alzheimer’s disease (AD) is one of the most common chronic neurodegenerative disorders worldwide. It is characterized by progressive memory loss and cognitive decline, leading to dementia. The pathogenesis of the disease is primarily attributed to two pathological protein structures: amyloid-beta (Aβ) plaques and tau protein neurofibrils. The current treatment strategies for AD are mainly symptomatic, highlighting the urgent need for the development of new, more effective therapies for the disease. The purpose of this paper is to provide a comprehensive and scientific review of the latest research regarding novel therapeutic options in the treatment of AD. In recent years, research has focused on more advanced and diversified strategies, including immunotherapy, gene therapy, tyrosine kinase inhibitors, therapies targeting mitochondrial function, and neurogenesis-related process modulation. One of the most promising treatment strategies for AD is immunotherapy. Intensive research is currently underway on both passive immunization, which involves the administration of monoclonal antibodies, and active immunization through vaccinations that stimulate the body to produce specific antibodies. Further research into novel therapeutic directions is essential, particularly concerning the role of the immune system in the pathogenesis of AD. Immunization appears to be a highly promising approach to developing effective methods for preventing AD or delaying the progression of this disease. Full article

Cucurbita pepo (CP) seeds are traditionally used to alleviate lower urinary tract symptoms associated with benign prostatic hyperplasia and overactive bladder. While these effects are often attributed to lipophilic constituents, recent studies have highlighted the therapeutic potential of oil-free hydroethanolic extracts. However, their composition remains insufficiently characterized, considering the species’ significant phenotypic and phytochemical variability. This study aimed to characterize the phytochemical profile of hydrophilic hydroethanolic seed extracts from ten CP cultivars originating from different European regions, with a focus on compositional variability. The elemental composition, along with primary and secondary metabolites, was analyzed using established spectroscopic and chromatographic methods. The extracts showed considerable variation in protein (45.39 to 114.58 mg/g dw) and free amino acid content (46.51 to 111.10 mg/g dw), as well as differences in elemental composition. Principal component analysis revealed distinct clustering patterns, with several samples displaying metabolite profiles comparable to the Cucurbita pepo var. styriaca variety currently recommended by the European Pharmacopoeia (Ph. Eur.) and the Committee on Herbal Medicinal Products (HMPC). These findings open the possibility of using other CP varieties as alternative sources for extract preparation and offer novel insights into the composition of less explored hydrophilic extracts derived from CP seeds. Full article

Osteoporosis is a multifactorial, polygenic disease characterized by reduced bone mineral density (BMD) and increased fracture risk. Genome-wide association studies (GWASs) have identified numerous loci associated with BMD and/or bone fractures, but functional characterization of these target genes is essential to understand the biological mechanisms underlying osteoporosis. This review focuses on current methodologies and key examples of successful functional studies aimed at evaluating gene function in osteoporosis research. Functional evaluation typically follows a multi-step approach. In silico analyses using omics datasets expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and DNA methylation quantitative trait loci (mQTLs) help prioritize candidate genes and predict relevant biological pathways. In vitro models, including immortalized bone-derived cell lines and primary mesenchymal stem cells (MSCs), are used to explore gene function in osteogenesis. Advanced three-dimensional culture systems provide additional physiological relevance for studying bone-related cellular processes. In situ analyses of patient-derived bone and muscle tissues offer validation in a disease-relevant context, while in vivo studies using mouse and zebrafish models enable comprehensive assessment of gene function in skeletal development and maintenance. Integration of these complementary methodologies helps translate GWAS findings into biological insights and supports the identification of novel therapeutic targets for osteoporosis. Full article