Search Results (1,887)

The central cholinergic system is an important player in the control of motor function, appetite, the reward system, attention, memory and learning. Its participation in neurological diseases (e.g., Alzheimer’s and Parkinson’s disease, epilepsy) and in psychiatric diseases (e.g., schizophrenia, depression) makes it a preferred study subject for drug development. The present review summarizes salient features of the central cholinergic synapses that will guide future studies. Cholinergic synapses are defined by the presence of choline acetyltransferase (ChAT), the vesicular ACh transporter (VAChT), the high-affinity choline transporter CHT-1 and the presence of PRiMA-coupled acetylcholinesterase (AChE). The firing frequency of cholinergic fibers is reflected in high-affinity choline uptake activity, which also responds to variations in ChAT, VAChT and AChE activities conferring considerable plasticity to cholinergic responses. The availability of glucose and choline can limit ACh synthesis and release under conditions of high ACh turnover. Future studies will focus on rapid methods to measure ACh release and a deeper understanding of cholinergic plasticity during development, aging and dementia. Full article

Alzheimer’s disease (AD) is a progressive neurological condition with limited effective pharmaceutical treatments, often accompanied by side effects. This has increased interest in plant-based alternatives. This study examined the cognitive effects of a Natural Polyherbal Extract (NPX) on scopolamine-induced memory deficits in mice. Male C57BL/6 mice (10 weeks old, n = 36) were divided into four groups: control (saline), scopolamine (1 mg/kg, i.p.), tacrine (10 mg/kg, oral), and NPX (1000 mg/kg, oral). NPX and tacrine were administered daily by oral gavage for two weeks. Cognitive function was assessed weekly using the Y-maze task. Brain tissues were collected for biochemical analysis, including AChE activity and immunohistochemical detection of neurodegeneration-related markers. Results: Mice treated with NPX demonstrated improved spontaneous alternation behavior compared to the scopolamine group. NPX also significantly reduced acetylcholinesterase activity. Immunohistochemistry revealed decreased expression of amyloid-beta (Aβ) and caspase-3, with enhanced choline acetyltransferase levels. These outcomes were comparable to those observed in the tacrine-treated group. Conclusions: NPX alleviated scopolamine-induced memory impairment through enhancement of cholinergic signaling and mitigation of neurodegenerative markers. The findings suggest that NPX may serve as a promising plant-derived candidate for managing memory-related disorders, including AD. Full article

This study establishes an efficient and eco-friendly ultrasound-assisted extraction (UAE) method for total flavonoids present in Cercis chinensis seeds using natural deep eutectic solvents (NADES). Among nine NADES formulations screened, choline chloride–levulinic acid (ChCl–Lev, 1:2) demonstrated optimal performance, yielding 112.1 mg/g total flavonoids. Through Response Surface Methodology (RSM), the ultrasound-assisted extraction (UAE) parameters were explored. Under the optimized conditions (water content of 30%, time of 28 min, temperature of 60 °C, and solvent-to-solid ratio of 1:25 g/mL), the total flavonoid yield reached 128.5 mg/g, representing a 195% improvement compared to conventional ethanol extraction. The recyclability of NADES was successfully achieved via AB-8 macroporous resin, retaining 80.89% efficiency after three cycles. Extraction kinetics, modeled using Fick’s second law, confirmed that the rate constant (k) increased with temperature, highlighting temperature-dependent diffusivity as a key driver of efficiency. The extracted flavonoids exhibited potent antioxidant activity, with IC₅₀ values of 0.86 mg/mL (ABTS•⁺) and 0.69 mg/mL (PTIO•). This work presents a sustainable NADES-UAE platform for flavonoid recovery and offers comprehensive mechanistic and practical insights for green extraction of plant bioactives. Full article

A pathogenic fungus was isolated from the leaves of strawberry black spot in Zhengzhou China. Based on morphological and phylogenetic analysis, the isolate was identified as Alternaria alstroemeriae. Hybrid sequencing and assembly yielded a high-quality 38.7 Mb genome with 12,781 predicted genes and 99.6% Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness. Functional annotation revealed enrichment in carbohydrate metabolism, secondary metabolite biosynthesis, and virulence-associated genes. Strain L6 harbored 45 biosynthetic gene clusters(BGCs), including 12 clusters for terpenes, 7 for non-ribosomal peptide synthetases, and 7 for polyketide synthases. Six BGCs showed high similarity to known pathways producing alternariol (phytotoxic/mycotoxic compound), alternapyrone (phytotoxin), choline (osmoprotectant), terpestacin (anti-angiogenic agent), clavaric acid (anticancer terpenoid), and betaenone derivatives (phytotoxins). CAZyme analysis identified 596 carbohydrate-active enzymes, aligning with L6’s biotrophic lifestyle. Additionally, 996 secreted proteins were predicted, of which five candidate effectors contained the conserved RxLx [EDQ] host-targeting motif, suggesting potential roles in virulence. This genome resource highlights L6’s exceptional secondary metabolites (SMs) diversity, featuring both plant-pathogenic toxins and pharmacologically valuable compounds, indicating that this endophytic fungus is a potential producer of metabolites meriting further exploration and development. Full article

Background: Parathyromatosis, an exceptional clinical and pathological entity, involves multiple small nodules of hyper-functional parathyroid tissue scattered throughout the neck and/or mediastinum, in relationship with a prior parathyroidectomy (mostly) or embryologic remnant. Since its first identification in 1975, many aspects of this condition have remained a matter of debate. Objective: We introduce an updated perspective on parathyromatosis covering the main clinical points for everyday practice, from diagnosis to management, as well as the current level of pathogenic understanding. Methods: A narrative review. Results: A total of 22 patients were identified, with the following characteristics: an age range of 33–68 (mean 46.18) years; 4/22 subjects <40 years; female-to-male ratio = 14:8. Of the 22 subjects, 21 had undergone previous parathyroidectomy for primary (n = 14) or secondary (n = 7) hyperparathyroidism. One case was a surgically naïve patient. Analysis of the surgical procedures (seeding circumstances) revealed the following: parathyroid cyst removal, left/right parathyroidectomy; removal of 3.5 parathyroids ± self-transplantation, VATS for mediastinal parathyroid tumours. Parathyroidectomy was accompanied by thyroid surgery (n = 3 patients), specifically hemi-thyroidectomy, partial left-thyroid lobectomy, and partial thyroidectomy. The shortest timeframe from parathyroidectomy to parathyromatosis-related hyperparathyroidism recognition was 1 year, and the longest was 17 years. The highest number of previous surgeries was four. The recognition of parathyromatosis was due to the clinical picture of associated hyperparathyroidism, except for in 2/21 cases with incidental detection. The implant sites coincided with the prior surgical area, but also with unusual locations (clavicle, pleura, mediastinum, sternocleidomastoid muscle and forearm, thyroid). The imaging evaluation included ultrasound plus CT plus 99m-Tc sestamibi scintigraphy, as well as (variable rates) neck MRI, SPECT/CT, 11-Choline PET-CT, Gallium-68 DOTATATE, and 4D CT. Surgery implied serial procedures in some cases (e.g., up to seven). The surgery spectrum largely varied, including not only cervicotomy, but also thoracoscopy, VATS, pericardial adipose tissue excision and thymectomy, etc. Conclusions: Awareness remains a key factor when approaching such an unusual ailment underlying little-understood pathogenic loops, which, if left unrecognized and untreated, might impair patients’ quality of life and the overall parathyroid disease burden. Full article

Gut microbiota has increasingly been shown to exert effects beyond the gastrointestinal tract, some of which are mediated through its metabolites, such as trimethylamine N-oxide (TMAO)—a compound converted by gut bacteria from dietary choline found predominantly in animal products that is associated with cardiovascular disease (CVD). However, a significant gap persists in human clinical trials assessing its potential causal role. This narrative review aims to present the current understanding of the gut microbiome, TMAO, and their relationship with CVD, while proposing future directions that may support the use of TMAO as a biomarker and guide potential interventions to reduce its harmful impact. Both animal and human studies have demonstrated a link between TMAO and CVD, with animal studies also indicating a causal effect—showing increased cardiovascular risk following TMAO administration and reduced risk when TMAO is eliminated. While direct extrapolation from animal models to humans is limited due to biological differences, these findings offer a foundation for the development of well-designed clinical trials in human populations. Although direct approaches to target TMAO—such as trimethylamine (TMA) lyase inhibitors and antisense oligonucleotide (ASO) therapy—have shown promising results in animal studies, they have yet to be investigated in human trials, leaving indirect strategies such as dietary changes and probiotics as the only currently available options. Full article

The signal transducer and activator of transcription 3 (STAT3) in myeloid cells suppresses proinflammatory cytokine production and reduces collagen deposition. However, its role in methionine- and choline-deficient (MCD) diet-fed mice remains unclear. This study investigates the effects of myeloid-specific STAT3 deficiency on hepatic inflammation and fibrosis in MCD diet-fed mice. Myeloid-specific STAT3 knockout (mSTAT3KO) mice were fed the MCD diet for four weeks to induce metabolic dysfunction-associated steatohepatitis (MASH). MCD diet-fed mice displayed MASH-like pathological phenotypes, including hepatic steatosis, inflammation, and fibrosis. Compared with MCD diet-fed WT mice, mSTAT3KO mice fed the MCD diet exhibited reduced hepatic lipid accumulation but increased fibrosis. Notably, mSTAT3KO mice showed elevated hepatic STAT3 and lipocalin-2 (LCN2) protein levels in hepatocytes. Some proinflammatory cytokines were increased by the MCD diet in mSTAT3KO mice, which also exhibited increased hepatocyte apoptosis. Conversely, MCD diet-induced CD36, perilipin-2, acyl-CoA thioesterase 2, and 4-hydroxynonenal proteins were reduced by mSTAT3KO. Myeloid-specific STAT3 deficiency may induce a compensatory STAT3/LCN2 axis in hepatocytes, thereby exacerbating MASH progression. Full article

Cervical cancer (CC) represents a major public health concern, ranking as the fourth most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among middle-aged women worldwide. CC is caused by persistent infection with high-risk human papillomaviruses (HR-HPVs), with HPV 16 being the cause of more than 50% of CC cases. In this study, the exometabolome of the HPV 16-positive cell lines SiHa and Ca Ski, as well as the HPV 16-negative control cell line C-33 A, was evaluated. The exometabolome was validated through molecular signatures using a transcriptomic approach to identify genes encoding cellular metabolic enzymes. The exometabolome was analyzed using ¹H nuclear magnetic resonance spectroscopy (¹H-NMR). Exometabolomic profiles were subsequently compared through both multivariate and univariate statistical analyses to identify significant differences between cell lines. Molecular signatures were analyzed from the GSE9750 dataset obtained from the GEO database. Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan. An expression analysis showed increased expression of enzymes involved in amino acid synthesis, the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, galactose metabolism, and HIF-1α. These data suggest metabolites and metabolism-associated genes that can be used as non-invasive, stable diagnostic and prognostic biomarkers, as well as therapeutic targets for CC in the presence of HPV 16. Full article

This study presents an integrated valorization strategy for oat husks through microwave-assisted pretreatment using a deep eutectic solvent (DES) composed of choline chloride and glycerol (1:2). The process was designed to enhance the release of fermentable sugars, enable xylooligosaccharide (XOS) production, and support inulinase production by Aspergillus niger A42 via submerged fermentation of the hydrolysate and solid-state fermentation of the residual biomass. Response surface methodology (RSM) was applied to evaluate the effects of microwave power, treatment time, and liquid-to-solid ratio (LSR) on fermentable sugar content (FSC) and total phenolic compounds (TPCs). Following pretreatment, the biomass was hydrolyzed using 1.99% sulfuric acid for 1 min. Optimal pretreatment conditions (350 W, 30 s, LSR 4 w/w) yielded an FSC of 51.14 g/L. Additionally, 230.78 mg/L xylohexaose and 6.47 mg/L xylotetraose were detected. Submerged fermentation of the liquid fraction with A. niger A42 resulted in inulinase and invertase activities of 60.45 U/mL and 21.83 U/mL, respectively. Solid-state fermentation of the pretreated solids produced 37.03 U/mL inulinase and 17.64 U/mL invertase. The integration of microwave-assisted DES pretreatment, dilute acid hydrolysis, and fungal fermentation established a robust strategy for the sequential production of XOS, fermentable sugars, and inulinase from oat husks, supporting their comprehensive utilization within a sustainable biorefinery framework. Full article

This study explores the challenge of using anthocyanin-rich natural deep eutectic solvent (NADES) extracts to produce electrospun nanofibers for biodegradable freshness indicators. Red cabbage was extracted with two choline chloride-based NADESs (with citric or lactic acid), modified with 10–50% ethanol to lower viscosity, and compared with a standard 50% ethanol-water solvent. The citric acid NADES with 30% ethanol gave the highest anthocyanin yield (approx. 0.312 mg/mL, more than 20 times higher than the ethanol extract at approx. 0.014 mg/mL). For fiber fabrication, a polymer carrier blend of poly(ethylene oxide) (PEO) and sodium alginate (Alg) was employed, known to form hydrogen-bonded networks that promote chain entanglement and facilitate electrospinning. Despite this, the NADES extracts could not be electrospun into nanofibers, while the ethanol extract produced continuous, smooth fibers with diameters of approximately 100 nm. This highlights a clear trade-off; NADESs improve anthocyanin recovery, but their high viscosity and low volatility prevent fiber formation under standard electrospinning conditions. To leverage the benefits of NADES extracts, future work could focus on hybrid systems, such as multilayer films, core-shell fibers, or microcapsules, where the extracts are stabilized without relying solely on direct electrospinning. In storage tests, ethanol-extract nanofibers acted as effective pH-responsive indicators, showing visible color change from day 4 of meat storage. At the same time, alginate films with NADES extract remained unchanged after 12 days. These results highlight the importance of striking a balance between chemical stability and sensing sensitivity when designing anthocyanin-based smart packaging. Full article

This study reports the synthesis and characterization of well-defined ionic graft conjugates acting as drug delivery systems, based on monomeric ionic units derived from choline methacrylate (TMAMA) biofunctionalized with the anions of ampicillin (AMP) or cloxacillin (CLX). Using the “grafting from” technique with multifunctional macroinitiators, the density of side chains was precisely defined, and the length of side chains was well-controlled during polymerization. The resulting ionic conjugates featured the regulated content of ionic fractions with drug anions reaching up to 55% and drug content up to 48–70% for AMP, 27–65% for CLX, and 47–79% for (CLX + AMP). The drug release behavior was evaluated under physiological conditions using a dialysis method. The ionic conjugates demonstrated release efficiencies of 70–93% for CLX (5–16 µg/mL), 69–98% for AMP (12–13 µg/mL) in single systems, and 61–73% for CLX + AMP (10–15 µg/mL) in dual systems. Additionally, polymer surface properties were evaluated via water contact angle measurements (WCA = 30–54°). In an aqueous solution, the polymer self-assemblies appeared to be nanosized particles (90–360 nm). The results demonstrate that the synthesized TMAMA-based graft copolymers act as effective ionic conjugates and dual drug systems, offering a promising platform for controlled and multi-drug delivery applications. Full article

Parkinson’s Disease (PD) is the fastest-growing neurological disorder, characterized by the degeneration of dopaminergic neurons. Treatments remain symptomatic, and objective biomarkers for therapeutic response are lacking. This review aims to evaluate the potential of Proton Magnetic Resonance Spectroscopy (¹H-MRS) to provide objective and reproducible biomarkers for monitoring treatment response in PD. This systematic review followed PRISMA guidelines. Articles were searched in PubMed, Web of Science, Scopus, and Embase, and studies employing ¹H-MRS to evaluate pharmacological treatments in PD were included, analyzing pre- and post-treatment changes. Six studies were included, investigating cannabinoids, dopamine agonists, monoamine oxidase B inhibitors, and levodopa. Key metabolites analyzed were N-acetylaspartate, Creatine, Choline, myo-Inositol, and Glx (glutamate+glutamine). Increases in NAA, a marker of neuronal integrity and mitochondrial function, suggested neuroprotective mechanisms of dopaminergic drugs, while stable Cho and mI levels, markers of membrane metabolism and inflammatory processes, suggested limited short-term responsiveness. This is the first systematic review evaluating ¹H-MRS for monitoring neurometabolic changes induced by pharmacological treatments in PD. Observed metabolite changes appear to reflect treatment mechanisms and potential neuroprotective properties. Findings suggest that ¹H-MRS may serve as an objective biomarker for assessing therapeutic efficacy and potential neuroprotective drug effects, although further studies are needed to confirm its clinical utility. Full article

Considering the increased risk of cognitive deficits and mood disorders programming associated with bisphenol exposure, we used a preclinical model to identify short- and long-term effects of early exposure to Bisphenol A (BPA) and its replacement, Bisphenol S (BPS), on the central cholinergic and serotonergic systems. Wistar female and male rats born to dams exposed to BPA or BPS (both at 10 μg/kg/day or 50 μg/kg/day) during pregnancy and lactation were euthanized at weaning or adulthood. Cholinergic and serotonergic biomarkers were assessed in the frontal cortex and pons + medulla oblongata. BPA and BPS disrupted these systems, with outcomes depending on the specific bisphenol, biomarker, and time point. Effects also varied across brain regions and between sexes. The nicotinic cholinergic receptor showed more pronounced alterations than the presynaptic choline transporter. Both serotonergic receptors—5-HT1AR and 5-HT2R—were affected; however, the serotonergic transporter remained unchanged. Increased binding was the predominant effect for both systems. Maternal exposure to BPA, even at low doses, induces sex-dependent short- and long-term changes in the cholinergic and serotonergic systems of the progeny. BPS affects these same neurotransmitter systems, although leading to compound-specific outcomes. These results pose both BPA and BPS as neurotoxicants that compromise neurodevelopment and program disorders later in life. Full article

Sperm membrane lipids play a crucial role in male fertility, influencing sperm motility, viability, and functional competence. This study comprehensively characterizes the phospholipid and sphingolipid composition in highly motile human spermatozoa obtained through the swim-up method, a widely used technique in assisted reproductive technology (ART). Using two-dimensional thin-layer chromatography and phosphorus analysis, we identified choline glycerophospholipids (CGP, 45%), ethanolamine glycerophospholipids (EGP, 26%), and sphingomyelin (SM, 17%) as predominant phospholipids, with minor components including cardiolipin, lysophospholipids, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and neutral lipids. Gas chromatography analysis of glycerophospholipids (GPL) revealed a high long chain (C20–C22) polyunsaturated fatty acids (PUFA) content (46.3%), particularly docosahexaenoic acid (DHA, 22:6n-3), which was more abundant in CGP (46%) than EGP (26%). Sphingolipid analysis indicated that ceramide (Cer) and SM shared similar fatty acid profiles due to their metabolic relationship, with very-long-chain (VLC) PUFA (≥C26) being more prevalent in SM (10%) than in Cer (6%). Additionally, argentation chromatography identified highly unsaturated VLCPUFA species in Cer, including 28:3n-6, 28:4n-6, and 30:4n-6, which had not been previously quantified in motile human spermatozoa. Given the essential function of sphingolipid metabolism in spermatogenesis, capacitation, and acrosomal exocytosis, our findings suggest that the balance of VLCPUFA-containing SM and Cer could play a role in sperm performance and fertilization potential. This study provides novel insights into the lipid signature of human sperm and highlights the relevance of membrane lipid remodeling for male fertility and ART outcomes. Full article

As a major source of high-quality protein in China, duck meat such as the renowned Beijing Duck plays a critical role in the poultry industry. Sansui duck, a prized native breed, is valued for its tender meat and rich flavor, yet molecular mechanisms underlying its meat quality remain poorly studied. This study employed metabolomics and proteomics techniques to conduct a comprehensive comparative analysis of the breast and thigh muscles from 90-day-old (90X, 90T) and 468-day-old (468X, 468T) Sansui ducks. The meat quality traits indicated that the shear force and redness (a*) were significantly higher in the 468T and 468X groups compared to the 90X and 90T groups (p < 0.05). Similarly, the shear force values of the 90T and 468T groups were significantly higher than those of the 90X and 468X groups (p < 0.05). Quantitative proteomics analysis revealed differentially expressed proteins (DEPs) significantly enriched in oxidative phosphorylation and ribosomal biogenesis pathways. Non-targeted metabolomics identified differentially expressed metabolites (DEMs) concentrated in amino acid and lipid metabolism pathways. Correlation analysis indicated that in the comparison between 90X and 468X, 18 DEPs and 10 DEMs were closely associated with fleshiness, whereas in the comparison between 468X and 468T, 23 DEPs and 19 DEMs were closely associated with fleshiness. Integrating proteomics and metabolomics data analysis, proteins such as A0A8B9TTI1, R0JRM6, and A0A8B9SQI5, along with metabolites including L-lysine, L-pyrrolidone, and γ-aminobutyric acid from lysine degradation, butanoate metabolism, and 2-oxocarboxylic acid metabolism pathways, can be proposed as key factors influencing meat quality through pathways including lysine degradation, butanoate metabolism, and 2-oxocarboxylic acid metabolism in older ducks. In contrast, the protein R0JXJ3 and metabolites choline and L-glutamine may determine meat quality differences between anatomical sites through the ABC transporter pathway. These findings provide molecular insights and potential biomarkers for genetic breeding and meat quality improvement in Sansui ducks. Full article