ABSTRACT
The Sapindus saponaria (soapberry) kernel is rich in oil that has antibacterial, anti-inflammatory, and antioxidant properties, promotes cell proliferation, cell migration, and stimulates skin wound-healing effects. S. saponaria oil has excellent lubricating properties and is a high-quality raw material for biodiesel and premium lubricants, showing great potential in industrial and medical applications. Metabolite and transcriptome analysis revealed patterns of oil accumulation and composition and differentially expressed genes (DEGs) during seed development. Morphological observations of soapberry fruits at different developmental stages were conducted, and the oil content and fatty acid composition of the kernels were determined. Transcriptome sequencing was performed on kernels at 70, 100, and 130 days after flowering (DAF). The oil content of soapberry kernels was lowest at 60 DAF (5%) and peaked at 130 DAF (31%). Following soapberry fruit-ripening, the primary fatty acids in the kernels were C18:1 (oleic acid) and C18:3 (linolenic acid), accounting for an average proportion of 62% and 18%, respectively. The average contents of unsaturated fatty acids and saturated fatty acids in the kernel were 86% and 14%, respectively. Through the dynamic changes in fatty acid composition and DEGs analysis of soapberry kernels, FATA, KCR1, ECR, FAD2 and FAD3 were identified as candidate genes contributing to a high proportion of C18:1 and C18:3, while DGAT3 emerged as a key candidate gene for TAG biosynthesis. The combined analysis of transcriptome and metabolism unveiled the molecular mechanism of oil accumulation, leading to the creation of a metabolic pathway pattern diagram for oil biosynthesis in S. saponaria kernels. The study of soapberry fruit development, kernel oil accumulation, and the molecular mechanism of oil biosynthesis holds great significance in increasing oil yield and improving oil quality.
ABSTRACT
Chicken meat is highly perishable and mainly preserved by plastic packaging materials, whereas their widely used have increased environmental burden and threatened human health. Bioactive packaging materials fabricated by biopolymers are promising alternatives for meat preservation. Herein, cassava starch (CS)/sodium carboxymethyl cellulose (CMC) edible films fortified with Litsea cubeba essential oil (LC-EO) were fabricated and characterized. Results showed the textural, mechanical and barrier properties of the CS/CMC edible films were significantly improved after incorporating with LC-EO. Moreover, the composite edible films exhibited potent antibacterial properties, biodegradability, hydrophobicity, and thermal stability. Whereas the water solubility and moisture content was reduced up to 29.68 % and 24.37 %, respectively. The release behavior of LC-EO suggested the suitability of the composite edible films for acidic foods. Comparing with the control group, the pH values of the meat samples packaged with CS/CMC/LCEO-4 mg/mL edible films maintained at around 6.7, and weight loss rate was 15 %. The color and texture changes, and the lipid oxidation of the meat samples with CS/CMC/LCEO-4 mg/mL packaging were also markedly delayed. The microbial growth was retarded at 6.35 log CFU/g after storage for 10 days. These findings suggested the CS/CMC/LCEO-4 mg/mL edible films had great potential for chicken meat preservation.
ABSTRACT
Symplocos paniculata are reported to exhibit seed dormancy, which impedes its cultivation and widespread adoption. In this study, a comprehensive method was established to overcome seed dormancy by subjecting seeds to scarification in 98% H2SO4 for 10 min, followed by 1000 mg·L-1 GA3 soaking for 48 h and stratification at 4 °C for 100 days. The seed germination percentage has increased significantly, to a peak of 42.67%, though the seeds could not germinate timely by NaOH scarification. Additionally, the dynamic changes of key stored substances (proteins, soluble sugars, starches, and fats), associated enzyme activities (amylases, peroxidase, and catalase), and endogenous hormones (abscisic acid, gibberellic acid, and indole-3-acetic acid) in seeds were investigated. The results demonstrated a continuous degradation of starch and fat in S. paniculata seeds, while the levels of protein and soluble sugar exhibited fluctuations, which probably facilitated seed dormancy breaking through energy supply and transformation. The enzymatic activities underwent rapid changes, accompanied by a gradual decrease in ABA content within the seeds with increasing stratification time. Notably, GA3, GA3/ABA, and (GA3 + IAA)/ABA showed significant increases, indicating their positive regulatory roles in seed germination. This study clarified the dormancy mechanism and established an effective method for the release dormancy of S. paniculata seeds.
ABSTRACT
Lead (Pb) affects gene transcription, metabolite biosynthesis and growth in plants. The tung tree (Vernicia fordii) is highly adaptive to adversity, whereas the mechanisms underlying its response to Pb remain uncertain. In this work, transcriptomic and metabolomic analyses were employed to study tung trees under Pb stress. The results showed that the biomass of tung seedlings decreased with increasing Pb doses, and excessive Pb doses resulted in leaf wilting, root rot, and disruption of Pb homeostasis. Under non-excessive Pb stress, a significant change in the expression patterns of flavonoid biosynthesis genes was observed in the roots of tung seedlings, leading to changes in the accumulation of flavonoids in the roots, especially the upregulation of catechins, which can chelate Pb and reduce its toxicity in plants. In addition, Pb-stressed roots showed a large accumulation of VfWRKY55, VfWRKY75, and VfLRR1 transcripts, which were shown to be involved in the flavonoid biosynthesis pathway by gene module analysis. Overexpression of VfWRKY55, VfWRKY75, and VfLRR1 significantly increased catechin concentrations in tung roots, respectively. These data indicate that Pb stress-induced changes in the expression patterns of those genes regulate the accumulation of catechins. Our findings will help to clarify the molecular mechanism of Pb response in plants.
Subject(s)
Catechin , Lead , Transcriptome , Lead/toxicity , Lead/metabolism , Catechin/metabolism , Metabolomics , Gene Expression Regulation, Plant , Soil Pollutants/toxicity , Stress, Physiological , Plant Roots/metabolism , Plant Roots/genetics , Flavonoids/metabolismABSTRACT
BACKGROUND: G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms. METHODS: Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration. Atrial myocyte action potential duration and inward rectifying K+ current (IK1) were recorded using whole-cell patch clamps. Isolated cardiomyocytes were stained with Fluo-3/AM dye, and intracellular Ca2+ handling was examined by CCD camera. A mouse model of AF was established by Ang-II (angiotensin II) infusion. RESULTS: Spexin plasma levels in patients with AF were lower than those in subjects without AF, and knockout of spexin increased AF susceptibility in mice. In the atrium of SPX-KO mice, potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) and sarcolipin (SLN) were upregulated; meanwhile, IK1 current was increased and Ca2+ handling was impaired in isolated atrial myocytes of SPX-KO mice. GALR2-cKO mice, but not GALR1-cKO and GALR3-cKO mice, had a higher incidence of AF, which was associated with higher IK1 current and intracellular Ca2+ overload. The phosphorylation level of CREB (cyclic AMP responsive element binding protein 1) was upregulated in atrial tissues of SPX-KO and GALR2-cKO mice. Chromatin immunoprecipitation confirmed the recruitment of p-CREB to the proximal promoter regions of KCNJ2 and SLN. Finally, spexin treatment suppressed CREB signaling, decreased IK1 current and decreased intracellular Ca2+ overload, which thus reduced the inducibility of AF in Ang-II-infused mice. CONCLUSIONS: Spexin reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and thus downregulating KCNJ2 and SLN transcription by GALR2 receptor. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic avenue in the development of agents against atrial fibrillation.
Subject(s)
Atrial Fibrillation , Mice, Knockout , Myocytes, Cardiac , Peptide Hormones , Receptor, Galanin, Type 2 , Animals , Female , Humans , Male , Mice , Action Potentials/drug effects , Atrial Fibrillation/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Myocytes, Cardiac/metabolism , Peptide Hormones/metabolism , Receptor, Galanin, Type 2/metabolism , Receptor, Galanin, Type 2/genetics , Signal TransductionABSTRACT
Active packaging is a novel technology that utilizes active materials to interact with products and the environment, improving food shelf life. The purpose of this work was to fabricate a multifunctional film using Litsea cubeba essential oil (LC-EO) (1 %, 3 %, 5 %, and 7 %) as the active ingredient and pullulan(P)/tapioca starch (TS) as the carrier material. Adding essential oil improves the films properties, such as barrier ability, anti-oxidant, and antibacterial activity. However, tensile strength (TS) and elongation at break (EAB) were slightly reduced from 28.94 MPa to 11.29 MPa and 15.36 % to 12.19 %. The developed PTS3% films showed the best performance in mechanical properties, especially EAB (14.26 %), WVP (3.26 %) and OP (3.13 %), respectively. The inhibitory zone diameters in the agar-well diffusion test were 18.59 mm for Staphylococcus aureus and 17.32 mm for Escherichia coli. Further study was conducted to compare the preservation effects of film with low-density polyethylene bag (LDPE) on chilled beef. Remarkably, PTS3% film decreased the bacterial population in beef meat while maintaining the pH, color, texture, and TBARS levels within an acceptable range for ten days of storage at 4 °C rather than in a low-density polyethylene bag. The outcomes indicated the potential of PTS3% films in food packaging applications.
Subject(s)
Anti-Bacterial Agents , Food Packaging , Food Preservation , Glucans , Litsea , Manihot , Oils, Volatile , Starch , Starch/chemistry , Glucans/chemistry , Glucans/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Food Preservation/methods , Manihot/chemistry , Food Packaging/methods , Litsea/chemistry , Staphylococcus aureus/drug effects , Animals , Escherichia coli/drug effects , Microbial Sensitivity Tests , Antioxidants/chemistry , Antioxidants/pharmacology , Tensile Strength , Meat/microbiologyABSTRACT
The main objective of this study is to investigate the impact and mechanism of soy lecithin incorporation into the gelatin-cinnamaldehyde emulsion, focusing on how it influences emulsion stability during the electrospinning process. In this work, a cinnamaldehyde/gelatin/soy lecithin (CGS) fiber membrane with excellent antibacterial properties was successfully created. The addition of soy lecithin improves the stability of the emulsion and improves the loading performance and fiber morphology of the CGS fiber membrane. Fourier Transform infrared spectroscopy (FTIR) and urea addition confirmed that soy lecithin may strengthen the interface structure of gelatin in the oil and water phases through hydrogen bonds, thus enhancing the stability of the emulsion in electrospinning. The application tests also revealed that the CGS fiber membrane effectively preserved the sensory quality of beef. This study indicates that the vector construction method can extend the utilization of cinnamaldehyde in food industry.
Subject(s)
Acrolein , Acrolein/analogs & derivatives , Emulsions , Gelatin , Glycine max , Lecithins , Nanofibers , Acrolein/chemistry , Acrolein/pharmacology , Gelatin/chemistry , Emulsions/chemistry , Lecithins/chemistry , Nanofibers/chemistry , Glycine max/chemistry , Animals , Cattle , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacologyABSTRACT
Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.
Subject(s)
Body Temperature , Nociception , TRPV Cation Channels , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Animals , Mice , Allosteric Regulation/drug effects , Nociception/drug effects , Nociception/physiology , Body Temperature/drug effects , Analgesics/pharmacology , Male , Humans , Mice, Inbred C57BL , Mice, Knockout , Pain/metabolism , Pain/drug therapyABSTRACT
The objective of this study was to systematically elucidate the effects of conventional (Cold Pressing, CP; Hot Pressing, HP; Soxhlet Extraction; SE) and novel methods (Microwave-Assisted Extraction, MAE) on the physicochemical properties, bio-active substances, flavor and lipidomics of Camellia oleifera oil (COO). The cold-pressed COO contained the highest contents of squalene (176.38 mg/kg), α-tocopherol (330.52 mg/kg), polyphenols (68.33 mg/kg) and phytosterols (2782.55 mg/kg). Oleic acid was observed as the predominant fatty acid with the content of approximately 80%. HS-GC-IMS identified 47 volatile compounds, including 11 aldehydes, 11 ketones, 11 alcohols, 2 acids, 8 esters, 2 pyrazines, 1 furan, and 1 thiophene. A total of 5 lipid classes and 30 lipid subclasses of 339 lipids were identifed, among which TGs and DGs were observed as the major lipids. In summary, both cold-pressed and microwave-assisted technologies provided high-quality COO with high content of bio-active substances and diglycerides/triglycerides.
Subject(s)
Camellia , Lipidomics , Plant Oils/chemistry , Fatty Acids , Oleic Acid , Camellia/chemistryABSTRACT
Foaming pretreatment has been proven effective in promoting sludge drying, however, the variation in sludge properties significantly influences the foaming efficiency. Inspired by foam stabilizer of solid particles, Camellia oleifera shells (COS) was screened out from various biomasses as an additive incorporated with the CaO for promoting the sludge foaming. For the introduction of COS, this study analyzed the drying behaviors of foamed sludge, quantified the surface cracks information, characterized the combustion performance, and evaluated the energy consumption. The results indicated that 46.72-50.10% of time could be saved in foaming the sludge to 0.70 g/mL by addition of 3.0 wt% COS. Compared with the original sludge (OS), the 0.70 g/mL foamed sludge saved 47.43% of time for sludge drying at 80 °C, and this value further increased to 53.14% with 3.0 wt% COS addition. Combining the multifractal spectra and drying kinetics analysis, the foaming promoted the formation of complex surface cracks in the warm-up period, while COS further improved the complexity of cracks in the constant rate period, and the shrinkage of isolated sludge blocks in the falling rate period, thus enhanced the moisture diffusion and heat transfer. Furthermore, the appropriate porous structure and additional volatile matters promoted the combustion performance. The 0.90 g/mL foamed sludge with COS presented the lowest activation energy of 180.362 kJ/mol in combustion. Overall, compared with OS, the 0.70 g/mL foamed sludge with COS saved 40.65% energy consumption during the foaming, drying and combustion processes, providing an energy-efficient solution for the sludge treatment and disposal.
Subject(s)
Camellia , Sewage , Sewage/chemistry , Desiccation/methods , Hot Temperature , KineticsABSTRACT
The increasing risk of food poisoning caused by Staphylococcus aureus (S. aureus) contamination has aroused great concern about food safety. Eugenol is highly favored due to its broad-spectrum antibacterial activity and non-drug resistance property. The study aimed to reveal the anti-bacterial and anti-virulence mechanisms of eugenol against S. aureus using phosphoproteomics. The results indicated that eugenol could inhibit the phosphorylation levels of enzyme I in the bacterial phosphotransferase system (PTS). Meanwhile, it could also inhibit the phosphorylation levels of key enzymes in bacterial carbon metabolism (such as glucose-6-phosphate isomerase of glycolysis and succinyl-CoA synthetase of tricarboxylic acid cycle), thereby decreasing the content of ATP and accelerating bacterial death. In addition, eugenol could inhibit the phosphorylation of AgrA in the quorum sensing system, thereby inhibiting the expression of agr operons (agrA and agrC) and downstream virulence genes (RNAIII, hla and seb). Finally, the application on beef indicated that eugenol could effectively decrease the content of enterotoxins and improve its storage quality. These findings provide a new way for eugenol to prevent S. aureus contamination and food poisoning in meat products.
Subject(s)
Foodborne Diseases , Meat Products , Staphylococcal Infections , Animals , Cattle , Humans , Staphylococcus aureus , Virulence , Eugenol/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Staphylococcal Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Quorum SensingABSTRACT
Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen often found in ready-to-eat (RTE) foods, posing significant threats to human health. In this study, an active film based on cross-linking via Schiff base and electrostatic interaction to inactivate L. monocytogenes on RTE foods was constructed. Zinc-casein hydrolysate chelates (Zn-HCas) was prepared and blended with cationic starch (CSt) to form the substrates of the film. Then, Citral (CI) with excellent antibacterial properties was added to enhance the biological and packaging properties of the film through covalent cross-linking (Schiff base). Based on the zinc ion-activated metalloproteinases produced by L. monocytogenes, the cross-linked film could be disrupted and the release of CI was accelerated. The variation in color, FTIR, and amino group content proved that Schiff base reaction had taken place. Enhanced mechanical properties, barrier properties, thermal stability and antimicrobial activity against L. monocytogenes (exceed 99.99 %) were obtained from the CI/Zn-HCas/CSt film. The application on RTE cheese results demonstrated that the cross-linked film could be employed in active packaging field with the ability in maintaining the original chroma and texture properties of RTE cheese. In summary, the prepared cross-linked film could be used as an active packaging against L. monocytogenes contamination with great potential.
Subject(s)
Acyclic Monoterpenes , Caseins , Listeria monocytogenes , Meat Products , Humans , Starch , Food Packaging/methods , Zinc , Schiff Bases , Food Microbiology , Meat Products/microbiologyABSTRACT
Staphylococcus aureus (S. aureus) enterotoxins have aroused great concern to food safety owing to its increased risk of food poisoning. The current research aimed to investigate the anti-virulence mechanisms of phloretin against S. aureus in terms of toxin activity and gene expression. The results indicated that phloretin could effectively inhibit the production of hemolysins and enterotoxins, and its anti-virulence effect was exerted in a concentration-dependent manner. Transcriptome results indicated that phloretin could downregulate the transcription level of majority virulence factors related genes (68 %) of S. aureus, including the quorum sensing-related genes (agrB, agrC, agrA, sspA, splF, splD and others) and bacterial secretion system-related genes (secDF, secY2, and yidC). In addition, it was speculated that phloretin was most likely to bind to the AgrA DNA binding domain, thereby affecting the expression of downstream virulence genes (hla, seb, spa, rot, geh, etc) based on molecular docking. Finally, the application in cooked chicken indicated that phloretin could effectively decrease the content of enterotoxins and improve the storage quality of cooked chicken. These findings not only evidenced the feasible anti-virulence activity of phloretin, but also provided a new strategy to prevent S. aureus food poisoning in cooked meat preservation.
Subject(s)
Foodborne Diseases , Staphylococcal Infections , Animals , Staphylococcus aureus , Virulence/genetics , Chickens/microbiology , Molecular Docking Simulation , Phloretin/pharmacology , Phloretin/metabolism , Enterotoxins/genetics , Enterotoxins/metabolism , Staphylococcal Infections/microbiology , Gene Expression Profiling , Anti-Bacterial Agents/pharmacologyABSTRACT
Cardiomyocyte maturation is the final stage of heart development, and abnormal cardiomyocyte maturation will lead to serious heart diseases. CXXC zinc finger protein 1 (Cfp1), a key epigenetic factor in multi-lineage cell development, remains underexplored in its influence on cardiomyocyte maturation. This study investigates the role and mechanisms of Cfp1 in this context. Cardiomyocyte-specific Cfp1 knockout (Cfp1-cKO) mice died within 4 weeks of birth. Cardiomyocytes derived from Cfp1-cKO mice showed an inhibited maturation phenotype, characterized by structural, metabolic, contractile, and cell cycle abnormalities. In contrast, cardiomyocyte-specific Cfp1 transgenic (Cfp1-TG) mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) overexpressing Cfp1 displayed a more mature phenotype. Mechanistically, deficiency of Cfp1 led to a reduction in trimethylation on lysine 4 of histone H3 (H3K4me3) modification, accompanied by the formation of ectopic H3K4me3. Furthermore, Cfp1 deletion decreased the level of H3K4me3 modification in adult genes and increased the level of H3K4me3 modification in fetal genes. Collectively, Cfp1 modulates the expression of genes crucial to cardiomyocyte maturation by regulating histone H3K4me3 modification, thereby intricately influencing the maturation process. This study implicates Cfp1 as an important molecule regulating cardiomyocyte maturation, with its dysfunction strongly linked to cardiac disease.
Subject(s)
Histones , Induced Pluripotent Stem Cells , Animals , Humans , Mice , Histones/genetics , Induced Pluripotent Stem Cells/metabolism , Myocytes, Cardiac/metabolism , Trans-Activators/genetics , Trans-Activators/metabolismABSTRACT
Lotus seed drill core powder starch (LCPS)-based active packaging films incorporated with cellulose nanocrystals (CNC) and grapefruit essential oil-corn nanostarch Pickering emulsion (ECPE) were characterized, and their pork preservation effects were investigated in this study. In contrast with corn, potato and rice starches, LCPS showed higher amylose content, elliptical and circular shape with more uniform size distribution. Furthermore, LCPS film exhibited lower light transmittance, stronger tensile strength, and smaller elongation at break compared to the other starch films. Then, the LCPS film containing 4 % CNC and 9 % ECPE was fabricated which had stronger mechanical properties, lower water vapor permeability and oxygen transmission rate, and denser network structure. FTIR and XRD analyses also confirmed that CNC and ECPE were successfully implanted into the LCPS matrix without damaging the crystalline structure of LCPS. Herein, the LCPS/CNC/ECPE film exerted potential antibacterial activity against Escherichia coli and Staphylococcus aureus. Besides, packaging with this composite film significantly preserved the pork during cold storage via decreasing its juice loss rate, pH value, total number of colonies, total volatile base nitrogen and thiobarbituric acid reactive substance values. The present study will provide a theoretical basis for the application of LCPS as new biodegradable active films.
Subject(s)
Pork Meat , Red Meat , Animals , Swine , Starch/chemistry , Powders , Food Packaging , Cellulose/chemistry , Escherichia coli , PermeabilityABSTRACT
`The objective of current research was to encapsulate citrus bergamia essential oil (CBEO) in nanocomplexes composed of sodium caseinate (SC) and peach gum polysaccharide (PG) in various ratios (SC/PG-1:0, 0:1, 1:1, 1:3, and 3:1). The nanocomplexes formed by the combination of SC and PG in a ratio of 1:3 exhibited a zeta potential of -21.36 mV and a PDI of 0.25. The CBEO-loaded SC/PG (1:3) nanocomplexes revealed the maximum encapsulation efficiency (82.47 %) and loading capacity (1.85 %). FTIR also confirmed the secondary structure variations in response to different ratios of CBEO-loaded SC/PG nanocomplexes. In addition, the XRD and fluorescence spectroscopy analysis also revealed structural changes among CBEO nanocomplexes. The thermal capability of CBEO-loaded SC/PG (1:3) nanocomplexes via TGA showed the minimum weight loss among other complexes. SEM and CLSM analysis demonstrated the uniform distribution and spherical morphology of CBEO-loaded SC/PG (1:3) nanocomplexes. The antioxidant activity of free CBEO was significantly improved in CBEO-loaded nanocomplexes. Likewise, the inhibitory activity of CBEO-loaded nanocomplexes exhibited significantly higher antibacterial action against S. aureus and E. coli. The aforementioned perspective suggests that SC/PG nanocomplexes have potent potential to serve as highly effective nanocarriers with a broad spectrum of uses in the pharmaceutical and food sectors.
Subject(s)
Citrus , Oils, Volatile , Prunus persica , Caseins/chemistry , Escherichia coli , Staphylococcus aureus , Oils, Volatile/pharmacology , Oils, Volatile/chemistryABSTRACT
Apricot polysaccharides (APs) as new types of natural carriers for encapsulating and delivering active pharmaceutical ingredients can achieve high-value utilization of apricot pulp and improve the solubility, the stability, and the antibacterial activity of insoluble compounds simultaneously. In this research, the purified APs reacted with bovine serum albumin (BSA) by the Maillard reaction, and with d-α-tocopheryl succinate (TOS) and pheophorbide A (PheoA) by grafting to fabricate two materials for the preparation of curcumin (Cur)-encapsulated AP-BSA nanoparticles (CABNs) and Cur-embedded TOS-AP-PheoA micelles (CTAPMs), respectively. The biological activities of two Cur nano-delivery systems were evaluated. APs consisted of arabinose (22.36%), galactose (7.88%), glucose (34.46%), and galacturonic acid (31.32%) after the optimized extraction. Transmission electron microscopy characterization of CABNs and CTAPMs displayed a discrete and non-aggregated morphology with a spherical shape. Compared to the unencapsulated Cur, the release rates of CABNs and CTAPMs decreased from 87% to 70% at 3 h and from 92% to 25% at 48 h, respectively. The antioxidant capacities of CABNs and CTAPMs were significantly improved. The CTAPMs exhibited a better antibacterial effect against Escherichia coli than CABNs due to the synergistic photosensitive effect between Cur and PheoA.
Subject(s)
Curcumin , Nanoparticles , Prunus armeniaca , Curcumin/pharmacology , Drug Carriers , Polysaccharides/pharmacology , Particle SizeABSTRACT
Foodborne diseases caused by Staphylococcus aureus contamination on meat and meat products has gained increasing attention in recent years, while the pathogenicity of S. aureus is mainly attributed to its virulence factors production, which is primarily regulated by quorum sensing (QS) system. Herein, we aimed to uncover the inhibitory effects and mechanisms of citral (CIT) on virulence factors production by S. aureus, and further explore its potential application in pork preservation. Susceptibility test confirmed the antibacterial properties of CIT against S. aureus, the minimal inhibitory concentration (MIC) was 0.25 mg/mL. Treatment with sub-MICs of CIT reduced the hemolytic activity by inhibiting the production of α-hemolysin, and staphylococcal enterotoxins (SEs) production was significantly inhibited by CIT in both culture medium and pork without affecting bacterial growth. Transcriptomic analysis indicated that the differentially expression genes encoding α-hemolysin, SEs, and other virulence factors were down-regulated after treatment with 1/2MIC CIT. Moreover, the genes related to QS including agrA and agrC were also down-regulated, while the global transcriptional regulator sarA was up-regulated. Data here demonstrated that CIT could inhibited S. aureus virulence factors production through disturbing QS systems. In a challenge test, the addition of CIT caused a remarkable inhibition of S. aureus population and delay in lipid oxidation and color change on pork after 15 days incubation at 4 °C. These findings demonstrated that CIT could not only efficiently restrain the production of S. aureus virulence factors by disturbing QS, but also exhibit the potential application on the preservation of meat products.
Subject(s)
Acyclic Monoterpenes , Staphylococcal Infections , Staphylococcus aureus , Humans , Virulence Factors/genetics , Virulence Factors/metabolism , Hemolysin Proteins , Bacterial Proteins/metabolism , Enterotoxins/metabolism , Meat , Staphylococcal Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolismABSTRACT
P2X receptors (P2X1-7) are non-selective cation channels involved in many physiological activities such as synaptic transmission, immunological modulation, and cardiovascular function. These receptors share a conserved mechanism to sense extracellular ATP. TNP-ATP is an ATP derivative acting as a nonselective competitive P2X antagonist. Understanding how it occupies the orthosteric site in the absence of agonism may help reveal the key allostery during P2X gating. However, TNP-ATP/P2X complexes (TNP-ATP/human P2X3 (hP2X3) and TNP-ATP/chicken P2X7 (ckP2X7)) with distinct conformations and different mechanisms of action have been proposed. Whether these represent species and subtype variations or experimental differences remains unclear. Here, we show that a common mechanism of TNP-ATP recognition exists for the P2X family members by combining enhanced conformation sampling, engineered disulfide bond analysis, and covalent occupancy. In this model, the polar triphosphate moiety of TNP-ATP interacts with the orthosteric site, while its TNP-moiety is deeply embedded in the head and dorsal fin (DF) interface, creating a restrictive allostery in these two domains that results in a partly enlarged yet ion-impermeable pore. Similar results were obtained from multiple P2X subtypes of different species, including ckP2X7, hP2X3, rat P2X2 (rP2X2), and human P2X1 (hP2X1). Thus, TNP-ATP uses a common mechanism for P2X recognition and modulation by restricting the movements of the head and DF domains which are essential for P2X activation. This knowledge is applicable to the development of new P2X inhibitors.
ABSTRACT
BACKGROUND AND PURPOSE: The P2X3 receptor, a trimeric ionotropic purinergic receptor, has emerged as a potential therapeutic target for refractory chronic cough (RCC). Nevertheless, gefapixant/AF-219, the only marketed P2X3 receptor antagonist, might lead taste disorders by modulating the human P2X2/3 (hP2X2/3) heterotrimer. Hence, in RCC drug development, compounds exhibiting strong affinity for the hP2X3 homotrimer and a weak affinity for the hP2X2/3 heterotrimer hold promise. An example of such a molecule is sivopixant/S-600918, a clinical Phase II RCC candidate with a reduced incidence of taste disturbance compared to gefapixant. Sivopixant and its analogue, (3-(4-([3-chloro-4-isopropoxyphenyl]amino)-3-(4-methylbenzyl)-2,6-dioxo-3,6-dihydro-1,3,5-triazin-1(2H)-yl)propanoic acid (DDTPA), exhibit both high affinity and high selectivity for hP2X3 homotrimers, compared with hP2X2/3 heterotrimers. The mechanism underlying the druggable site and its high selectivity remains unclear. EXPERIMENTAL APPROACH: To analyse mechanisms that distinguish this drug candidate from other inhibitors of the P2X3 receptors we used a combination of chimera construction, site covalent occupation, metadynamics, mutagenesis and whole-cell recording. KEY RESULTS: The high affinity and selectivity of sivopixant/DDTPA for hP2X3 receptors was determined by the tri-symmetric site located close to the upper vestibule. Substitution of only four amino acids inside the upper body domain of hP2X2 with those of hP2X3, enabled the hP2X2/3 heterotrimer to exhibit a similar level of apparent affinity for sivopixant/DDTPA as the hP2X3 homotrimer. CONCLUSION AND IMPLICATIONS: From the receptor-ligand recognition perspective, we have elucidated the molecular basis of novel RCC clinical candidates' cough-suppressing properties and reduced side effects, offering a promising approach to the discovery of novel drugs that specifically target P2X3 receptors.