Search Results (337)

In recent years, as the number of cats has increased, the intestinal health of cats has receied increasing amounts of attention. Probiotics have positive effects on maintaining intestinal homeostasis. This study was conducted to investigate the effects of probiotics Bacillus licheniformis (B. licheniformis) and Bacillus subtilis (B. subtilis) on cat immunity, inflammation, antioxidants, intestinal barrier and microbiota, and serum metabolites. Thirty-six cats (over one year old, 3.48 ± 0.71 kg) were randomly divided into 3 groups and fed with a basal diet (CON group), a basal diet + B. licheniformis (BL group), and a basal diet + B. subtilis (BS Group). The experiment lasted 35 days. Fecal scoring indicates that B. licheniformis and B. subtilis can improve fecal scores. Serum analysis indicated that the addition of both substances increased levels of IgA, IgM, T-AOC, and SOD, while reducing levels of the pro-inflammatory factor TNF-α. Moreover, 16S rRNA gene sequencing revealed that B. licheniformis and B. subtilis altered the fecal microbiota composition, characterized by the elevated abundance of Bacillus. Adding B. licheniformis to the diet increased the level of Faecalibacterium and decreased the level of Mogibacterium. Serum metabolomics revealed that levels of L-Glycine and Sn-Glycero-3-phosphocholine exhibited marked elevation in both the BL and BS groups, respectively. Furthermore, the study demonstrated that differential metabolites in the BL group were mainly enriched in amino acid metabolism pathways, while those in the BS group were chiefly concentrated in lipid metabolism pathways. However, this study acknowledges the limitations of its exclusive use of Ragdoll cats and its 35-day intervention period. It highlights the need for future research involving diverse breeds and longer durations. Overall, the data highlight B. licheniformis and B. subtilis as cat nutritional supplements that improve immunity and maintain intestinal health. Full article

Background/Objectives: The prebiotic effect of resistant potato starch (RPS) has been demonstrated, but the role of this nutrient in choline metabolism and the production of microbially modified choline-derived toxins is unknown. Methods: We performed post hoc analysis comparing changes in choline and related metabolites in serum from baseline to the week 4 time point in a human clinical trial evaluating daily consumption of 3.5 g RPS versus a placebo. Results: Choline levels increased in the RPS consuming group, while levels of trimethylamine decreased and levels of the cardiovascular toxin trimethylamine oxide were unaffected by RPS consumption. Increases in choline were positively correlated with increases in Akkermansia in the gut. Oxidation of choline to betaine was unaffected by RPS, as was acetylcholine metabolism. Levels of various saturated even acyl chain and hydroxylated acyl chain sphingomyelins were increased in RPS consuming participants, and levels of phospholipid degradation products phosphocholine and glycerophosphocholine were decreased. Conclusions: These data suggest that RPS enhances choline absorption without increasing TMAO and stimulates the incorporation of choline into sphingomyelins containing saturated even acyl chains and hydroxylated acyl chains. Future studies assessing the physiological consequences, such as cognitive or neurological benefits, of enhanced choline absorption and sphingomyelin levels in people consuming RPS are warranted. Full article

Phosphoethanolamine N-methyltransferase (PEAMT) is a key enzyme that catalyzes three successive methylation steps of phosphoethanolamine (P-EA) to phosphocholine (P-Cho). Meanwhile, P-Cho is a major precursor of phosphatidylcholine (PC) and glycine betaine (GB), which are involved in cell signal transduction, stress response, etc. Therefore, the PEAMT gene plays an essential role in plant growth and development as well as stress resistance. There are two homologous PEAMT genes in rice (Oryza sativa L. ssp. japonica), namely, OsPEAMT1 and OsPEAMT2. However, there has not been any comprehensive functional analysis of these two genes. Here, we employed bioinformatics methods to analyze the amino acid sequences and promoters of OsPEAMT1 and OsPEAMT2, and found that both proteins contain two methyltransferase domains. OsPEAMT1 is highly similar with ZmPEAMT, and OsPEAMT2 is closely related to LmPEAMT and TaPEAMT. There are abundant plant hormone response elements, stress response elements and low-temperature response elements in the promoters of OsPEAMT1 and OsPEAMT2. The in vitro enzymatic activity assays of recombinant proteins of OsPEAMT1 and OsPEAMT2 indicated that they can catalyze the production of P-Cho from P-EA, respectively. Meanwhile, the endogenous P-Cho content increased significantly (p < 0.05) when exogenous P-EA was added to rice. These indicate that OsPEAMT1 and OsPEAMT2 proteins have catalytic functions in vivo and in vitro. The expression patterns of both genes are different in different tissues, flowers and seeds at various developmental stages. Additionally, both genes have different responses to salt and low-temperature stress. This study supplies valuable insights into the function of OsPEAMT1 and OsPEAMT2, and it will provide key targets for rice molecular breeding, offering important insights for the development of rice with stress resistance and high yield. Full article

The interaction between carbon nanoparticles (CNs) and Langmuir monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a model pulmonary surfactant (PS) film was studied to shed light on the physicochemical bases underlying the potential adverse effects associated with pollutant inhalation. The results indicated that the surface pressure–area isotherms of the DPPC monolayers shifted toward lower molecular areas, and the compression modulus was reduced in the presence of CNs, hindering the ability of the DPPC monolayers to reduce the surface tension. The relaxation process of the DPPC monolayers were influenced, and the surface morphology and the continuity of the monolayers were destroyed by the penetration of CNs into the DPPC monolayers. The molecular dynamics simulation revealed that particle incorporation into the DPPC monolayers reduced the packing density of the DPPC molecules, worsening the mechanical performance of the monolayers. This effect was attributed to the strong binding trend between the CNs and the DPPC molecules. These results demonstrated that CNs could alter the relaxation mechanisms of the PS film, and this may cause a modification of the inhaled particle transport at the PS film and contribute to adverse health effects in the respiratory system of workers involved in the CN production process. Full article

This study used NMR-based metabolomics to investigate the mode of action (MoA) of 6-hydroxydopamine (6-OHDA) toxicity in the SH-SY5Y neuroblastoma cell model. 6-OHDA, a structural analogue of dopamine, has been used to create a Parkinson’s disease model since 1968. Its selective uptake via catecholaminergic transporters leads to intracellular oxidative stress and mitochondrial dysfunction. SH-SY5Y cells were treated with 6-OHDA at its IC₅₀ concentration of 60 μM, and samples of treated and untreated groups were collected after 24 h. The endo metabolome was extracted using a methanol–water mixture, while the exo metabolome was represented by the culture media. Further, endo- and exo metabolomes of treated and untreated cells were analysed for metabolic changes. Our results demonstrated significantly high levels of glutathione, acetate, propionate, and NAD⁺, which are oxidative stress markers, enhanced due to ROS production in the system. In addition, alteration of myoinositol, taurine, and o-phosphocholine could be due to oxidative stress-induced membrane potential disturbance. Mitochondrial complex I inhibition causes electron transport chain (ETC) dysfunction. Changes in key metabolites of glycolysis and energy metabolism, such as glucose, pyruvate, lactate, creatine, creatine phosphate, glycine, and methionine, respectively, demonstrated ETC dysfunction. We also identified changes in amino acids such as glutamine, glutamate, and proline, followed by nucleotide metabolism such as uridine and uridine monophosphate levels, which were decreased in the treated group. Full article

Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article

Bestrophinopathies are a group of inherited retinal diseases caused by mutations in the BEST1 gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells. We have already demonstrated the surface behavior and organization of recombinant hBest1 and its interactions with membrane lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM) and cholesterol (Chol) in models of biological membranes, which affect the hBest1 structure–function relationship. The main aim of our current investigation is to integrate pure hBest1 protein into lipid bilayer nanostructures. We synthesized and characterized various hBest1-containing nanostructures based on 1,2-Dipalmitoylphosphatidylcholine (DPPC), SM, glycerol monooleate (GMO) and Chol in different ratios and determined their cytotoxicity and incorporation into cell membranes and/or cells by immunofluorescence staining. Our results show that these newly designed nanoparticles are not cytotoxic and that their incorporation into MDCK II cell membranes (used as a model system) may provide a mechanism that could be applied to RPE cells expressing mutated hBest1 in order to restore their ion transport functions, affected by mutated and malfunctioning hBest1 molecules. Full article

The amyloid-beta 1-42 (Aβ1-42) oligomers are the most cytotoxic species of the amyloid family and play a key role in the pathology of Alzheimer’s Disease (AD). They have been shown to damage cellular membranes, but the exact mechanism is complex and not well understood. Multiple routes of membrane damage have been proposed, including the formation of pores and ion channels. In this work, we study the membrane damage induced by Aβ1-42 oligomers using black lipid membrane (BLM) electrophysiology and compare their action with gramicidin, known to form ion channels. Our data show that Aβ1-42 oligomers can induce a variety of damage in the lipid membranes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and cholesterol (CHOL), including small ion channels, similar to the gramicidin channels, with an average inner diameter smaller than 5 Å. These channels have a short retaining time in lipid membranes, suggesting that they are highly dynamic. Our studies provide new insights into the mechanism of membrane damage caused by Aβ1-42 oligomers and extend the current perception of the Aβ channelopathy hypothesis. It provides a more in-depth understanding of the molecular mechanism by which small Aβ oligomers induce cytotoxicity by interacting with lipid membranes in AD. Full article

Monomeric C-reactive protein (mCRP), derived from the dissociation of the native pentameric CRP (pCRP), has been implicated in the pathophysiology of various neurological conditions, particularly intracerebral hemorrhage (ICH) and neurodegenerative diseases. mCRP accumulates in the brain after hemorrhagic stroke, contributing to the formation of the metabolic penumbra and promoting inflammation. Recent studies have linked mCRP to the activation of microglia, endothelial cells, and complement pathways, which collectively intensify neuroinflammation and disrupt tissue repair mechanisms. Additionally, mCRP is associated with cognitive decline, particularly in ICH survivors, by promoting microvascular damage, neurodegeneration, and vascular instability. The presence of mCRP in distant regions of the brain, including the hypothalamus, suggests its potential role in spreading inflammation and exacerbating long-term neurological damage. This review synthesizes findings on the pathogenic role of mCRP in stroke and neurodegeneration, proposing that mCRP could serve as both a biomarker and a therapeutic target for improving outcomes in stroke patients. Emerging immunopharmacological strategies are being actively pursued to mitigate the pathogenic activity of mCRP, a potent pro-inflammatory effector implicated in a variety of immune-mediated and neuroinflammatory conditions. These approaches encompass the inhibition of native pentameric CRP dissociation into its monomeric isoform, the disruption of mCRP’s high-affinity interactions with lipid rafts and cell surface receptors involved in innate immune activation, and the enhancement of its clearance through mechanisms such as solubilization, opsonin-mediated tagging, and phagocytic engagement. Targeting these immunoregulatory pathways offers a compelling therapeutic framework for attenuating mCRP-driven inflammatory cascades in both systemic and CNS-specific pathologies. Full article

Background: We report the successful formulation of a bone-targeted vancomycin-loaded liposomal carrier. Method: The basic liposomal structure is composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and dicetyl phosphate (DCP) in a molar ratio of 3:1:0.25, respectively. The dehydration–rehydration method was used to maximize the liposomal-encapsulation efficiency of vancomycin after the initial preparation using thin-film hydration. Results: Sodium alendronate was used as a targeting moiety and was successfully conjugated to DSPE–PEG–COOH via carbodiimide chemistry, as was confirmed using IR spectroscopy. The resulting conjugate, DSPE–PEG-alendronate, was subsequently used in the formulation of bone-targeting vancomycin-loaded liposomes. In vitro binding assays with hydroxyapatite demonstrated preferential binding of the surface-modified liposomes to hydroxyapatite crystals. Furthermore, ex vivo studies revealed that the surface-modified liposomes exhibited enhanced binding affinity to the tibial bone tissue of 4-week-old male CD1 mice, in comparison to unmodified liposomes. Conclusions: The successfully formulated surface-modified vancomycin loaded liposomes showed enhanced bone affinity with a great potential for targeting the antibiotic to infected bones. Full article

Peptides designed to interfere with specific steps of viral infection mechanisms have shown promising antiviral potential. In this study, we investigated the ability of a synthetic peptide (peptide 303), derived from the fusion protein sequence of the Infectious Salmon Anemia Virus (ISAV), to inhibit membrane fusion mediated by the ISAV fusion peptide (ISAV-FP1). To assess this, we employed a model membrane system consisting of large unilamellar vesicles (LUVs) composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), and cholesterol. Membrane fusion kinetics were monitored via R18 fluorescence dequenching. Additionally, the interaction of peptide 303 with lipid membranes was evaluated using fluorescence anisotropy measurements. The potential direct interaction between peptide 303 and ISAV-FP1 was further examined through Förster Resonance Energy Transfer (FRET) assays. Our results demonstrate that peptide 303 effectively inhibits ISAV-FP1-mediated membrane fusion. Furthermore, peptide 303 was shown to interact with lipid bilayers and with ISAV-FP1 itself. These findings suggest a dual inhibitory mechanism in which peptide 303 both prevents ISAV-FP1 binding to the membrane and directly interacts with the fusion peptide, thereby disrupting its fusogenic activity. Full article

Accurate diagnosis of diseases in patients is crucial, particularly in older individuals, where the focus is often placed primarily on advanced age and its associated symptoms. However, advancements in technology and research have revealed that certain diseases traditionally linked to aging can also manifest in younger populations, demonstrating similar bodily changes. One such condition is sarcopenia, a degenerative disease of skeletal muscle that arises from various pathological processes affecting the tissues. In this study, we developed a liposomal formulation based on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), in which both nicotinamide mononucleotide (NMN) and Matrigel (Mgel) were co-encapsulated, each playing a distinct role in the management of sarcopenia. NMN is known to stimulate the increase of NAD+ levels, while Matrigel enhances the activity of satellite cells, thereby facilitating muscle fiber regeneration and stabilizing protein levels. Results from the DLS, SEM, and TEM analyses revealed significant differences attributed to the type of therapeutic agent used and the synthesis parameters. Additionally, the drug release profile underscored the complementary nature and significance of selecting the appropriate active substances for effective treatment strategies. The in vitro investigations aimed to assess the potential of DMPC lipid vesicles loaded with NMN, either alone or in combination with Matrigel, to counteract sarcopenia-associated oxidative stress and mitochondrial dysfunction. The results showed that both NMN-based formulations reduced oxidative damage, preserved mitochondrial function, and maintained cytoskeletal integrity in a hydrogen peroxide-induced model of sarcopenia. Importantly, the formulation containing both NMN and Matrigel demonstrated superior protective effects, suggesting a synergistic role of the extracellular matrix components in enhancing muscle cell resilience. These findings support the use of DMPC-based delivery systems as promising candidates for sarcopenia therapy and warrant further investigation into their mechanisms of action in preventing muscle cell degeneration. Full article

Raman spectroscopy is one of the best techniques for obtaining information concerning the physical–chemical interactions between a lipid and a solvent. Phospholipids in water are the main elements of cell membranes and, by means of their chemical and physical structures, their cells can interact with other biological molecules (i.e., proteins and vitamins) and express their own biological functions. Phospholipids, due to their amphiphilic structure, form biomimetic membranes which are useful for studying cellular interactions and drug delivery. Synthetic systems such as DPhPC-based liposomes replicate the key properties of biological membranes. Among the different models, phospholipid mimetic membrane models of lamellar vesicles have been greatly supported. In this work, a biomimetic system, a deuterium solution (50 mM) of the synthetic phospholipid 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhDC), is studied using μ-Raman spectroscopy in a wide temperature range from −181.15 °C up to 22.15 °C, including the following temperatures: −181.15 °C, −146.15 °C, −111.15 °C, −76.15 °C, −61.15 °C, −46.15 °C, −31.15 °C, −16.15 °C, −1.15 °C, 14.15 °C, and 22.15 °C. Based on the Raman evidence, phase transitions as a function of temperature are shown and grouped into five classes, where the corresponding Raman modes describe the stretching of the (C−N) bond in the choline head group (gauche) and the asymmetric stretching of the (O−P−O) bond. The acquisition temperature of each Raman spectrum characterizes the rocking mode of the methylene of the acyl chain. These findings enhance our understanding of the role of artificial biomimetic lipids in complex phospholipid membranes and provide valuable insights for optimizing their use in biosensing applications. Although the phase stability of DPhPC is known, the collected Raman data suggest subtle molecular rearrangements, possibly due to hydration and second-order transitions, which are relevant for membrane modeling and biosensing applications. Full article

Gibberella root rot (GRR), caused by Fusarium graminearum, is one of the major threats to maize production. However, the mechanism underlying maize’s response to GRR is not fully understood. Multi-omics study incorporating metabolomics reveals insights into maize–pathogen interactions. Using metabolomics and mass spectrometry imaging (MSI), maize inbred lines with GRR resistance (W438) and susceptibility (335M) were deployed to characterize specific metabolites associated with GRR. Analysis of significantly altered metabolites suggested that glycerophospholipid metabolism was highly associated with GRR resistance or susceptibility. Furthermore, the distinct accumulation of lysophosphatidylethanolamine (lysoPE) and lysophosphatidylcholine (lysoPC) from glycerophospholipid metabolism, along with the significant up-regulation of phospholipase (PLA) gene in the susceptible line, suggested that high levels of lysoPC and lysoPE contributed to GRR susceptibility. Meanwhile, genes encoding lysophospholipase (LPLA), the detoxification enzymes of lysoPC, were significantly activated in both genotypes. However, the significantly higher expression of LPLAs in the resistant line corresponded to a significant increase in the content of non-toxic sn-glycero-3-phosphocholine, whereas this increase was not observed in the susceptible line. MSI analysis revealed the involvement of other potential phospholipids in GRR susceptibility. Taken together, maintaining an appropriate concentration of lysophospholipids is crucial for their role in the signaling pathway that triggers GRR resistance without causing damage to maize roots. Full article

Growing neurochemical evidence highlights cerebral lipid dysregulation as a key factor in the pathophysiology of major depressive disorder (MDD). This review systematically explores the dual roles of lipid species in both normal behavioral regulation and MDD development. By critically examining the recent literature, we classify these lipid species into two functional categories based on their functional neuroactivity: (1) neuroprotective lipids (sphingomyelin, cholesterol, cardiolipin, sphingosine, phosphatidic acid, and phosphatidylserine), which exert neuroprotective effects by modulating membrane fluidity and supporting synaptic vesicle trafficking; and (2) neurotoxic lipids (ceramides, phosphatidylinositol, phosphocholine, and phosphatidylethanolamine), which promote apoptotic signaling cascades and disrupt mitochondrial bioenergetics. An unresolved but critical question pertains to the maintenance of homeostatic equilibrium between these opposing lipid classes. This balance is essential, given their significant impact on membrane protein localization and function, monoaminergic neurotransmitter metabolism, energy homeostasis, and redox balance in neural circuits involved in mood regulation. This emerging framework positions cerebral lipidomics as a promising avenue for identifying novel therapeutic targets and developing biomarker-based diagnostic approaches for MDD treatment. Full article