Cubic liquid crystals containing propolis flavonoids as in situ thermo-sensitive hydrogel depots for periodontitis treatment: Preparation, pharmacodynamics and therapeutic mechanisms.

Propolis has a long ethnopharmacological history for oral periodontal diseases treatment. Propolis flavonoids are main active components for anti-inflammation and tissue protection. However, the intractable dissolution properties of propolis flavonoids and complex oral environment pose great challenges for periodontal delivery. In addition, the therapeutic mechanism as well as the therapeutic correlation of inflammation resolution and tissue regeneration remain unclear for propolis flavonoids. In this study, we constructed an in situ thermosensitive depot systems using total flavonoids from propolis-loaded cubic liquid crystals (TFP-CLC) hydrogel for periodontal delivery. TFP-CLC inhibited inflammatory cell infiltration, reactive oxygen species and the expression of inflammatory cytokines of NF-κB and IL-1ß. In addition, alveolar bone and collagen were significantly regenerated after TFP-CLC administration according to micro-CT and immunohistochemistry. Mechanism studies suggested that TFP-CLC alleviated inflammation and promoted alveolar bone repair via regulating TLR4/MyD88/NF-κB p65 and RANK/NF-κB signaling pathways, respectively. Correlation analysis further confirmed that the inflammatory resolution produced by TFP-CLC could accelerate periodontal tissue regeneration. In summary, TFP-CLC is a promising multifunctional in situ thermo-sensitive hydrogel depots for periodontitis treatment.

Orally administered dual-targeted astaxanthin nanoparticles as novel dietary supplements for alleviating hepatocyte oxidative stress.

The enhancement of bioavailability of food bioactive compounds as dietary supplements can be achieved through the development of targeted delivery systems. This study aimed to develop a novel dual-targeted delivery system for hepatocytes and mitochondria using phacoemulsification self-assembly. The delivery systems were engineered by modifying whey protein isolate (WPI) with galactose oligosaccharide (GOS) and triphenylphosphonium (TPP) to improve AXT transport to the liver and promote hepatic well-being. The dual-targeted nanoparticles (AXT@TPP-WPI-GOS) significantly reduced reactive oxygen species in in vitro experiments, thereby slowing down apoptosis. The AXT@TPP-WPI-GOS exhibited a prominent mitochondrial targeting capacity with a Pearson correlation coefficient of 0.76 at 4 h. In vivo pharmacokinetic experiments revealed that AXT@TPP-WPI-GOS could enhance AXT utilization by 28.18 ± 11.69%. Fluorescence imaging in mice demonstrated significantly higher levels of AXT@TPP-WPI-GOS accumulation in the liver compared to that of free AXT. Therefore, these nanoparticles hold promising applications in nutrient fortification, improving the bioavailability of AXT and supporting hepatic well-being.

Amelioration of obesity and inflammation by polysaccharide from unripe fruits of raspberry via gut microbiota regulation.

Raspberry, a traditional medicine food homology species, has important benefits in patients with metabolic syndrome. However, the mechanism of raspberry polysaccharides (RP) on obesity remains unclear. In our study, we showed that RP intervention is negatively associated with body weight gain, hyperlipidemia, inflammation, and fat accumulation in obese mice. RP ameliorated HFD-induced gut microbiota dysbiosis, produced short-chain fatty acids, maintained intestinal barrier integrity, and prevented metabolic endotoxemia, manifested by decreased host lipopolysaccharide level, and increased colon expression of tight junction proteins. These effects might be related with driven by a SCFAs-producing bacterium and downregulation of TLR4/NF-κB signaling transduction. Notably, the abundance of Ruminococcaceae_UCG - 014, Lactobacillus taiwanensis, Bifidobacterium pseudolongum, and Turicibacter are markedly correlated with enhanced intestinal barrier function induced by RP treatment. Thus, we believe that RP could be as a potential health supplement or prebiotic for obesity therapy.

Unveiling mechanisms of silicon-mediated resistance to chromium stress in rice using a newly-developed hierarchical system.

Silicon (Si) has been well-known to enhance plant resistance to heavy-metal stress. However, the mechanisms by which silicon mitigates heavy-metal stress in plants are not clear. In particular, information regarding the role of Si in mediating resistance to heavy-metal stress at a single cell level is still lacking. Here, we developed a hierarchical system comprising the plant, protoplast, and suspension cell subsystems to investigate the mechanisms by which silicon helps to alleviate the toxic effects of trivalent chromium [Cr(III)] in rice. Our results showed that in whole-plant subsystem silicon reduced shoot Cr(III) concentration, effectively alleviating Cr(III) stress in seedlings and causing changes in antioxidant enzyme activities similar to those observed at lower Cr(III) concentrations without silicon added. However, in protoplast subsystem lacking the cell wall, no silicon deposition occurred, leading to insignificant changes in cell survival or antioxidation processes under Cr(III) stress. Conversely, in suspension cell subsystem, silicon supplementation substantially improved cell survival and changes in antioxidant enzyme activities under Cr(III) stress. This is due to the fact that >95% of silicon was on the cell wall, reducing Cr(III) concentration in cells by 7.7%-10.4%. Collectively, the results suggested that the silicon deposited on the cell wall hindered Cr(III) bio-uptake, which consequently delayed Cr(III)-induced changes in antioxidant enzyme activities. This research emphasizes the significance of cell walls in Si-alleviated heavy-metal stress and deepens our understanding of silicon functioning in plants. Furthermore, the hierarchical system has great potential for application in studying the functioning of other elements in plant cell walls.

Flavonoid extract from propolis alleviates periodontitis by boosting periodontium regeneration and inflammation resolution via regulating TLR4/MyD88/NF-κB and RANK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, propolis has been used for treating oral diseases for centuries, widely. Flavonoid extract is the main active ingredient in propolis, which has attracted extensive attention in recent years. AIM OF THE STUDY: The objective and novelty of the current study aims to identify the mechanism of total flavonoid extract of propolis (TFP) for the treatment of periodontitis, and evaluate the therapeutic effect of TFP-loaded liquid crystal hydrogel (TFP-LLC) in rats with periodontitis. METHODS: In this study, we used lipopolysaccharide-stimulated periodontal ligament stem cells (PDLSCs) to construct in vitro inflammation model, and investigated the anti-inflammatory effect of TFP by expression levels of inflammatory factors. Osteogenic differentiation was assessed using alkaline phosphatase activity and alizarin red staining. Meanwhile, the expression of toll like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB), receptor activator of NF-κB (RANK) etc, were quantitated to investigate the therapeutic mechanism of TFP. Finally, we constructed TFP-LLC using a self-emulsification method and administered it to rats with periodontitis via periodontal pocket injection to evaluate the therapeutic effects. The therapeutic index, microcomputed tomography (Micro-CT), H&E staining, TRAP staining, and Masson staining were used for this evaluation. RESULTS: TFP reduced the expression of TLR4, MyD88, NF-κB and inflammatory factor in lipopolysaccharide-stimulated PDLSCs. Meanwhile, TFP simultaneously regulating alkaline phosphatase, RANK, runt-associated transcription factor-2 and matrix metalloproteinase production to accelerate osteogenic differentiation and collagen secretion. In addition, TFP-LLC can stably anchor to the periodontal lesion site and sustainably release TFP. After four weeks of treatment with TFP-LLC, we observed a decrease in the levels of NF-κB and interleukin-1ß (IL-1ß) in the periodontal tissues of rats, as well as a significant reduction in inflammation in HE staining. Similarly, Micro CT results showed that TFP-LLC could significantly inhibit alveolar bone resorption, increase bone mineral density (BMD) and reduce trabecular bone space (Tb.Sp) in rats with periodontitis. CONCLUSION: Collectively, we have firstly verified the therapeutic effects and mechanisms of TFP in PDLSCs for periodontitis treatment. Our results indicate that TFP perform anti-inflammatory and tissue repair activities through TLR4/MyD88/NF-κB and RANK/NF-κB pathways in PDLSCs. Meanwhile, for the first time, we employed LLC delivery system to load TFP for periodontitis treatment. The results showed that TFP-LLC could be effectively retained in the periodontal pocket and exerted a crucial role in inflammation resolution and periodontal tissue regeneration.

Silicon-phosphorus pathway mitigates heavy metal stress by buffering rhizosphere acidification.

Heavy metal pollution threatens food security, and rhizosphere acidification will increase the bioavailability of heavy metals. As a beneficial element in plants, silicon can relieve heavy metal stress. However, less attention has been paid to its effects on plant rhizosphere processes. Here, we show that for Japonica (Nipponbare and Oochikara) and Indica (Jinzao 47) rice cultivars, the degree of root acidification was significantly reduced after silicon uptake, and the total organic carbon, citric acid, and malic acid concentrations in rice root exudates were significantly reduced. We further confirmed the results by q-PCR that the expressions of proton pump and organic acid secretion genes were down-regulated by 35-61 % after silicon treatment. Intriguingly, phosphorus allocation, an intensively studied mechanism of rhizosphere acidification, was altered by silicon treatment. Specifically, among total phosphorus in rice seedlings, the soluble proportion increased from 52.0 % to 61.7 %, while cell wall phosphorus decreased from 48.0 % to 32.3 %. Additionally, silicon-mediated alleviation of rhizosphere acidification has positive effects on relieving heavy metal stress. Simulation revealed that low acidification of the nutrient solution resulted in a decrease in bioavailable heavy metal concentrations, thereby reducing rice uptake. We further confirmed that the impediment of rhizosphere acidification led to free-state Cr3+ in solutions decreasing by 43 % and contributed up to 63 % of silicon's mitigation of Cr(III) stress. Overall, we propose a novel mechanism in which silicon reduces heavy metal absorption by increasing plant soluble phosphorus concentration and buffering rhizosphere acidification. This paper provides a unique insight into the role of silicon in plants and, more importantly, a theoretical reference for the rational application of silicon fertilizer to improve phosphorus utilization efficiency, alleviate heavy metal stress, and balance soil pH.

Assembly and comparative analysis of the first complete mitochondrial genome of Acer truncatum Bunge: a woody oil-tree species producing nervonic acid.

BACKGROUND: Acer truncatum (purpleblow maple) is a woody tree species that produces seeds with high levels of valuable fatty acids (especially nervonic acid). The species is admired as a landscape plant with high developmental prospects and scientific research value. The A. truncatum chloroplast genome has recently been reported; however, the mitochondrial genome (mitogenome) is still unexplored. RESULTS: We characterized the A. truncatum mitogenome, which was assembled using reads from PacBio and Illumina sequencing platforms, performed a comparative analysis against different species of Acer. The circular mitogenome of A. truncatum has a length of 791,052 bp, with a base composition of 27.11% A, 27.21% T, 22.79% G, and 22.89% C. The A. truncatum mitogenome contains 62 genes, including 35 protein-coding genes, 23 tRNA genes and 4 rRNA genes. We also examined codon usage, sequence repeats, RNA editing and selective pressure in the A. truncatum mitogenome. To determine the evolutionary and taxonomic status of A. truncatum, we conducted a phylogenetic analysis based on the mitogenomes of A. truncatum and 25 other taxa. In addition, the gene migration from chloroplast and nuclear genomes to the mitogenome were analyzed. Finally, we developed a novel NAD1 intron indel marker for distinguishing several Acer species. CONCLUSIONS: In this study, we assembled and annotated the mitogenome of A. truncatum, a woody oil-tree species producing nervonic acid. The results of our analyses provide comprehensive information on the A. truncatum mitogenome, which would facilitate evolutionary research and molecular barcoding in Acer.

The formation process of green substances in Chrysanthemum morifolium tea.

One interesting phenomenon of Chrysanthemum morifolium tea is its formation of a green or dark green color after hours of brewing, and it is important to study the compounds that form this color and whether they might be involved in health benefits. Non-targeted metabolomics could clearly distinguish between green and non-green species by sparse partial least squares discriminant analysis (sPLS-DA) and heat-mapping. We found that the pH was the primary factor in the formation of the green color. Two green precursors (GP1 and GP2) were separated and purified with preparative HPLC. FT-IR analysis and the saccharide content analysis showed that GP1 had the typical characteristics of saccharides. GP2 was identified as chlorogenic acid by ESI-Q-TOF/MS and NMR. We raised the formation process of green substances was caused by the hydrolysates of chlorogenic acid reacting with glycosides or groups attached to the saccharides, which suggests a new mechanism for color-forming reactions.

Physicochemical and rheological properties of pomelo albedo pectin and its interaction with konjac glucomannan.

Pomelo albedo was extracted with water to obtain the high methoxyl pectin, labeled as PAP. The physicochemical and rheological properties of PAP were determined. The effects of PAP addition on rheological property and thermal stability of konjac glucomannan (KGM) were evaluated. Results indicated that PAP was composed of arabinose, glucose and galacturonic acid with a relative mass percentage of 7.2%: 9.5%: 83.3%, and exhibited an average molecular weight of 56.6 kDa. The degree of esterification of PAP was 65.5%, showing PAP was a kind of high methoxyl pectin. Apparent viscosity of PAP was concentration-dependently increased, while it was slightly enhanced with salt (NaCl or CaCl2) addition. Moreover, the addition of PAP declined the apparent viscosity, elastic property and thermal stability of KGM. It can be concluded that interaction was occurred between KGM and PAP. Meanwhile, the interaction mechanism between KGM and PAP has been preliminarily proposed. The present study can provide some references for the application of PAP and support the combination usage of this pectin and KGM in food and other industries.

The formation and bioactivities of green substances in Chrysanthemum morifolium tea.

One interesting phenomenon of Chrysanthemum morifolium tea is its formation of green or dark green color after hours of brewing. We investigated the greening reaction and its bioactivities, including an analysis of the green compounds. Results showed that the green color was due to a decrease in the L* (lightness), b* (yellowness/blueness), chroma values and an increase in hue angle. The green substances were found to be substances with similar polarities and unstable in acidic conditions. There was no significant difference (p < 0.01) in antioxidant activity between non-green and green samples. The green substances did not lead to cytotoxicity in PC12 cells at low concentrations, but at high concentrations, they caused a significant (p < 0.01) decrease in cell viability. The saccharide percentage and FT-IR results showed that the greening reaction was affected by the glycosides or groups attached to the saccharides, which might suggest a new mechanism for color-forming reactions.

Effect of Weakly Basic Conditions on the Separation and Purification of Flavonoids and Glycosides from Chrysanthemum morifolium Tea.

Tea brewed from chrysanthemum flowers has been widely used in Chinese medicine. The possibly medicinal compounds in Chrysanthemum morifolium tea can be purified by preparative high performance liquid chromatography (HPLC), but this is usually done with acidic conditions, which leads to the hydrolysis of glycosides. In hopes of avoiding this hydrolysis, we explored the effect of weakly basic conditions on the separation and purification of flavonoids and glycosides from Chrysanthemum morifolium. We also explored the effects of weakly basic conditions on chlorogenic acid (3-CQA) and apigenin-7-O-glucoside (A7G). Our results show that the concentration of the weakly basic ammonium hydrogen carbonate and time had no significant effect on A7G, p < 0.01, but it had a significant effect on 3-CQA, p < 0.01. HPLC and ultraviolet (UV) analysis showed that the structure of 3-CQA is destroyed in weakly basic conditions. Caffeic acid, quinic acid, and 3,4-dihydroxymandelic acid, which is a hydrolysate of 3-CQA, were identified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The results showed that weakly basic conditions could be used for the purification of flavonoids and glycosides but not for caffeoylquinic acids. Moreover, our work clarified the hydrolysis behaviour of caffeoylquinic acids, which can be helpful for research into their functional aspects.

Extraction, Purification, and Hydrolysis Behavior of Apigenin-7-O-Glucoside from Chrysanthemum Morifolium Tea.

Apigenin-7-O-glucoside is an active phenolic compound in Asteraceae flowers and possesses remarkable therapeutic applications. However, its high price and low abundance in plants limit its use, meanwhile it would hydrolyze in the purification process. In this study, apigenin-7-O-glucoside extracted with ultrasound and purified with preparative HPLC from Chrysanthemum morifolium 'Huangju' was investigated, as well as its hydrolysis behavior and bioactivities. The optimized extraction conditions were: solid/liquid ratio: 1:20, extraction time: 35 min, temperature: 50 °C, and ultrasound power: 350 W. The content of apigenin-7-O-glucoside was up to 16.04 mg/g. Apigenin-7-O-glucoside was then purified with preparative HPLC from the extract, and confirmed by Q-TOF/MS. Apigenin-7-O-glucoside was partially hydrolyzed in acidic condition, and the hydrolysis rate depended on the pH value and temperature. The antioxidant activity increased as a result of the hydrolysis process. This study provided a green and effective way to obtain apigenin-7-O-glucoside and would be beneficial for further investigations into nutritional and functional aspects apigenin-7-O-glucoside and other glycosides.

Screening of critical factors influencing the efficient hydrolysis of zeaxanthin dipalmitate in an adapted in vitro- digestion model.

As hydrolysis of carotenoid esters is believed to be highly efficient in vivo, their insufficient hydrolysis in in vitro-digestion models, particularly, regarding zeaxanthin diesters, is a current issue. Therefore, in this study, several factors related to the enzymatic hydrolysis were investigated in an adapted version of the standardized INFOGEST in vitro-digestion model, using zeaxanthin dipalmitate (ZDP) as a substrate. The results showed that pancreatic lipase was able to hydrolyze ZDP, whereas carboxyl ester lipase (CEL) substantially contributed to ZDP cleavage. Replacement of commonly used porcine with bovine bile extracts and the substitution of coffee creamer for soybean oil at identical fat contents both significantly improved hydrolysis efficiency and bioaccessibility of total zeaxanthin to better mimic in vivo conditions. Thus, bile and lipids selection for in vitro digestion of carotenoid esters was crucial. The combined use of coffee creamer, pancreatin, CEL, and bovine bile led to the highest hydrolysis efficiency of 29.5%.

Bidirectional Estrogen-Like Effects of Genistein on Murine Experimental Autoimmune Ovarian Disease.

This study was to investigate the bidirectional estrogen-like effects of genistein on murine experimental autoimmune ovarian disease (AOD). Female BALB/c mice were induced by immunization with a peptide from murine zona pellucida. The changes of estrous cycle, ovarian histomorphology were measured, and the levels of serum sex hormone were analyzed using radioimmunoassay. Proliferative responses of the ovary were also determined by immunohistochemistry. Administration of 25 or 45 mg/kg body weight genistein enhanced ovary development with changes in serum sex hormone levels and proliferative responses. Meanwhile, the proportions of growing and mature follicles increased and the incidence of autoimmune oophoritis decreased, which exhibited normal ovarian morphology in administration of 25 or 45 mg/kg body weight genistein, while a lower dose (5 mg/kg body weight genistein) produced the opposite effect. These findings suggest that genistein exerts bidirectional estrogen-like effects on murine experimental AOD, while a high dose (45 mg/kg body weight) of genistein may suppress AOD.

Separation and preparation of 6-gingerol from molecular distillation residue of Yunnan ginger rhizomes by high-speed counter-current chromatography and the antioxidant activity of ginger oils in vitro.

Molecular distillation residue (MD-R) from ginger had the most total phenol content of 247.6mg gallic acid equivalents per gram (GAE/g) among the ginger oils. High-speed counter-current chromatography (HSCCC) technique in semi-preparative scale was successfully performed in separation and purification of 6-gingerol from MD-R by using a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (10:2:5:7, v/v/v/v). The target compound was isolated, collected, purified by HSCCC in the head-tail mode, and then analyzed by HPLC. A total of 90.38±0.53mg 6-gingerol was obtained from 600mg MD-R, with purity of 99.6%. In addition, the structural identification of 6-gingerol was performed by EI/MS, (1)H NMR and (13)C NMR. Moreover, the orders of antioxidant activity were vitamin E (VE)>supercritical fluid extraction oleoresin (SFE-O)=MD-R=6-gingerol>molecular distillation essential oil (MD-EO) and butylated hydroxytoluene (BHT)=VE>6-gingerol>MD-R=SFE-O>MD-EO, respectively in 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging and ß-Carotene bleaching.

[Computer simulation study on physiological feedback parameters during chest compression].

To have a thorough understanding of the CPR quality based on patients' various physiological states, the doctors must do something to simulate the chest compression physiological feedback parameters (CCPFP). The CCPFP simulation plays an important role in raising efficiency of CPR training and improving chest compression quality. In this study, the CCPFP, including cardiac output (CO), coronary perfusion pressure (CPP), partial pressure of End-tidal CO2 (PETCO2) and mean arterial relaxation pressure (MARP), was simulated using Charles F. Babbs' Model. Simulation results showed that the effect of compression depth upon CCPFP was important in the range of 2-6 cm, whereas compression rate had little effect on the CCPFP higher than 100/min; the thoracic factor is inversely proportional to the CCPFP with fixed compression depth and compression rate. The CCPFP simulation can be implemented at the various physiological statuses, and verified well with the animal experimental results and the clinical results.