Isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate protects lipopolysaccharide-induced acute lung injury in mice by attenuating pyroptosis.

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills (CDDPs). Previous study showed that IDHP exerted anti-inflammatory effects by abolishing the secretion of proinflammatory factors stimulated by lipopolysaccharide (LPS). However, the effects of IDHP on LPS-induced acute lung injury (ALI) are not fully understood. In the present study, we observed the effects of IDHP on mortality and lung injury in LPS-treated mice and on LPS-induced THP-1 macrophages. Pretreatment with high dose of IDHP was found to reduce the mortality of ALI mice, significantly improve LPS-induced pathological changes, and reduce protein leakage and inhibited myeloperoxidase (MPO) activity in lung tissue. IDHP also inhibited the release of inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissue. Meanwhile, IDHP treatment significantly reduced the expression of active-caspase1, Nlrp3, Asc speck formation, Gsdmd (part of the canonical pyroptosis pathway), caspase4 (part of the non-canonical pyroptosis pathway), therefore decreasing IL-1ß, IL-18, and ROS secretion in LPS-stimulated THP-1 macrophages. Moreover, after co-culturing endothelial/epithelial cells with conditioned medium (CM) from LPS-stimulated THP-1 macrophages, we found that the protein levels of occludin and Zonula occludens-1 (Zo-1) were increased in IDHP CM-treated endothelial cells compared to those that were LPS CM-treated. Lactic dehydrogenase (LDH) assay shows that IDHP also alleviated LPS-induced endothelial/epithelial cell injury. These findings indicate that the protective effect of IDHP on LPS-induced lung injury may be partly due to the inhibition of pyroptosis pathways.

Responses of invasive and native plants to different forms and availability of phosphorus.

PREMISE: Many studies have assessed the various responses of alien plants to changes in overall nutrient or different nitrogen (N) availabilities. However, in natural soils, nutrients are present as different elements (e.g., N and phosphorus [P]) and forms (e.g., inorganic and organic). Few studies have explored whether invasive and native species differ in their responses to varying P availability and forms. METHODS: We grew five taxonomically related pairs of common herbaceous, invasive and native species alone or in competition under six different conditions of P availability or forms and assessed their growth performance. RESULTS: Invasive species overall did not produce more biomass than native species did in the various P conditions. However, the biomass response to organic forms of P was, relative to the response to inorganic forms of P, stronger for the invasive species than that for the native species and agreed with invasive species mainly allocating biomass to the root system under organic P conditions. CONCLUSIONS: While invasive species were not more promiscuous than the native species, they took great advantage of the organic P forms. Therefore, the invasion risk of alien species may increase in habitats with more organic P sources.

Dietary supplementation of Aspergillus niger-expressed glucose oxidase ameliorates weaning stress and improves growth performance in weaning pigs.

Weaning is one of the most stressful events in the pig's life, which disrupts physiological balance and leads to oxidative stress. It is reported that glucose oxidase supplementation could alleviate oxidative stress in animals by increasing the concentration of antioxidant enzymes in vivo. The purpose of this study was to evaluate the effects of dietary supplementation of Aspergillus niger-expressed glucose oxidase (AN-GOX) on growth performance, nutrient digestibility, faecal microbiota, faecal gas emission and serum antioxidant enzyme parameters in weaning pigs. A total of 120 21-day-old weaning pigs [(Yorkshire ×Landrace) × Duroc] with an initial body weight of 6.54 ± 0.55 kg were used in a 21-day experiment (phase 1, days 1-7; phase 2, days 8-21) with a completely randomized block design. Pigs were randomly divided into 4 treatment groups with 6 replicate pens per treatment and 5 pigs per pen (2 barrows and 3 gilts). Dietary treatments were corn-soybean meal-based basal diet supplemented with 0, 0.01, 0.03 or 0.05% AN-GOX (1000 unit/g). The results of this study showed that average daily gain during days 1-7 and 1-21 and the concentrations of serum glutathione peroxidase and glutathione increased linearly at graduated doses of AN-GOX increased in the diet. However, dietary supplementation of AN-GOX had no effects on the apparent nutrient digestibility, faecal microbiota and faecal gas emission. In conclusion, supplementing AN-GOX to the diet of weaning pigs ameliorated weaning stress, which manifested as the increase in serum antioxidant enzyme levels, thus improving growth performance. The suitable dosage of AN-GOX used in the diet of weaning pigs was 0.05%.

An "all-in-one" strategy based on the organic molecule DCN-4CQA for effective NIR-fluorescence-imaging-guided dual phototherapy.

Dual phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) is considered to be a more effective therapeutic method against cancer than single treatment. Therefore, the development of a single material with both near-infrared (NIR)-laser-triggered PDT and PTT abilities is highly desirable but remains a great challenge. A design philosophy for photosensitizers for integrated PDT and PTT treatment has been put forward: (1) a high molar extinction coefficient in the NIR region; (2) suitable LUMO and T1 energy levels to regulate intersystem crossing for effective singlet oxygen (1O2) generation for PDT; and (3) the suppression of fluorescence emission to enhance the process of nonradiative transition with appropriate chemical modifications. Herein, an "all-in-one" functional material, di-cyan substituted 5,12-dibutylquinacridone (DCN-4CQA), for diagnosis and therapy was obtained. DCN-4CQA possesses dual-functional phototherapeutic activity and NIR fluorescence and it was produced via a facile synthesis process from the classic organic photoelectric material quinacridone. We then prepared smart water-soluble nanoparticles (NPs), DCN-4CQA/F127, using Pluronic® 127 (F127) as a drug carrier. The NPs exhibited excellent biocompatibility, robust photostability, NIR fluorescence, a high photothermal conversion efficiency (η = 47.3%), and sufficient 1O2 generation (ΦΔ = 24.3%) under NIR laser irradiation. Remarkably, the DCN-4CQA/F127 NPs significantly inhibited tumor growth in mice subjected to NIR laser irradiation. This study provides a new route for the development of highly efficient, low-cytotoxicity photosensitizers for fluorescence-imaging-guided PTT/PDT.

Effects of housing systems and glucose oxidase on growth performance and intestinal health of Beijing You Chickens.

We investigated the effects of housing systems and dietary glucose oxidase (GOD) on the growth performance and intestinal health of Beijing You chickens (BYC). The experiment was designed as a factorial arrangement of 2 housing systems × 2 dietary treatments. Chickens were fed a basal diet or a diet with 200 U/kg GOD and were reared on the floor with deep litter or in the cages. Compared with the litter floor groups, the decreased average daily feed intake of 1 to 42 d, decreased feed conversion ratio (FCR), improved average daily gain of 42 to 77 d, and the whole period were identified in the cage rearing groups (P < 0.05). The FCR of 42 to 77 d and the whole period, the 42-d ileal pH, and 77-d jejunal and ileal pH decreased with the supplement of GOD (P < 0.05). Additionally, 16S rRNA gene of ileum contents was sequenced by high-throughput sequencing. Sequencing data indicated that the Firmicutes phylum of 42 d and the Bacteroidetes phylum were significantly higher in the litter group with GOD supplement (P < 0.05). The jejunal Occludin, Mucin-2 mRNA expression levels were higher in the litter floor groups than those in the cage rearing groups on 42 d (P < 0.05). The Mucin-2 and TNF-α mRNA expression levels increased with cage rearing on 77 d (P < 0.05). The Occludin and TLR-4 mRNA expression levels increased with the supplementation of GOD on 77 d (P < 0.05). Moreover, the upregulation effects of Occludin and ZO-1 mRNA expression levels were more obvious in the litter floor group fed with GOD diet on 77 d (P < 0.05). The serum endotoxin content of 42-day-old cage rearing groups were higher than that of the litter floor groups, and the serum endotoxin content significantly decreased with the supplement of GOD on 77 d. The results indicated that the litter floor systems were beneficial to the development of intestinal barrier junction in the early stage, but the cage systems were more conducive to the growth performance of BYC. The dietary GOD could inhibit the harmful bacteria and promote the beneficial bacteria, which might be related to the improvement of the growth performance and intestinal barrier function.

Effects of thermostable phytase supplemented in diets on growth performance and nutrient utilization of broilers.

Phytase is an enzyme that has the ability to release phosphorous (P) from phytate by hydrolyzing inositol-phosphate linkages. Recently, thermostable phytases have gained great consideration because the reduction in phytase activity was found when exposed to heat during feed pelleting. In this study, the effects of the granular thermostable phytase (Aspergillus niger) on growth performance and nutrient utilization of broilers were investigated. A total of 96 21-day-old Arbor Acres broilers were randomly distributed into six treatments including basal diet (control) and basal diet supplemented with 500, 1,000, 2,000, 4,000, 8,000 U of phytase/kg. In general, the metabolizable energy (ME) and the apparent and true availability of dry matter (DM), organic matter (OM), ether extract (EE), crude protein (CP), and amino acids (AA) showed both linearly (p < .01) and quadratically (p < .01) increase with increasing levels of phytase in the diet. Additionally, diet supplementation with phytase could improve (p < .05) body weight (BW), average daily gain (ADG), and feed/gain (F/G) on day 42 compared with the control. The results suggested that diet supplementation of the granular thermostable phytase in the crumbled pellets could improve chicken growth performance and nutrient utilization.

Pickering emulsions stabilized by luteolin micro-nano particles to improve the oxidative stability of pine nut oil.

BACKGROUND: Pine oil contains a high percentage of polyunsaturated fatty acids, which make it prone to oxidation. Luteolin (LUT) micro-nano particles with antioxidant properties can be used as stabilizers to form an edible oil-in-water Pickering emulsion to improve the oxidative stability of pine nut oil. RESULTS: Under optimal preparation conditions, the LUT micro-nano particles and pine nut oil account for about 0.44 and 90.9 g·kg-1 of the total mass of the emulsion, respectively. The LUT particles in the suspension have a mean particle size of about 479 nm, present a sheet-like structure with a cut surface of 30-50 nm, and can reduce the surface tension of deionized water. In the optimized Pickering emulsion, the emulsion droplets are approximately spherical and have a mean diameter of about 125.6 nm and uniform distribution. The optimized Pickering emulsion droplets can remain stable for up to 2 h in an environment where the pH levels are 7-8.5, ultraviolet B radiation (UVB) irradiation, of less than 5.0 g·kg-1 , and at a temperature of 80 °C. The stability of the emulsion in simulated digestive fluid changed minimally. In the first 7 days of the accelerated oxidation experiment, LUT micro-nano particles not only successfully protected the integrity of emulsion droplets but also fully inhibited the peroxidation of pine oil. CONCLUSION: The strong antioxidant properties of LUT micro-nano particles, and the dense protective layer they formed, stabilized the Pickering emulsion successfully. The particles also improved the oxidation stability of pine nut oil. © 2020 Society of Chemical Industry.

Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9.

Tumour metastasis is the major cause of breast cancer mortality. Myricetin, a natural polyphenol, is found in teas, wines, and berries. The pharmacodynamic action and molecular mechanism of myricetin on breast cancer metastasis remain unknown. Here, we investigated the effect of myricetin on MDA-Mb-231Br cell viability, migration, invasion, and 4T1 mouse lung metastasis mouse models. MMP-2/9 protein expression and ST6GALNAC5 expression were analysed using western blot assays and quantitative real-time polymerase chain reaction, respectively. Cell migration and invasion were detected by wound-healing and Boyden transwell assays. The antimetastatic effect in vivo was evaluated by lung metastasis model. Myricetin significantly decreased the activities of MMP-2/9 and mRNA levels of ST6GALNAC5. In addition, the migration, invasion, and adhesion were effectively inhibited in a concentration-dependent manner. On the other hand, mice treated with myricetin exhibited smaller tumour nodules compared with the vehicle mice, with only 17.78 ± 15.41% after treatment with 50 mg/kg myricetin. In conclusion, myricetin could significantly block invasion of MDA-Mb-231Br cells through suppressing the protein expression of MMP-2/9 and the expression of ST6GALNAC5, as well as lung metastasis in a mouse model, which suggests that myricetin should be developed as a potential therapeutic candidate for breast cancer.

Salvianolic acid Y: a new protector of PC12 cells against hydrogen peroxide-induced injury from Salvia officinalis.

Salvianolic acid Y (TSL 1), a new phenolic acid with the same planar structure as salvianolic acid B, was isolated from Salvia officinalis. The structural elucidation and stereochemistry determination were achieved by spectroscopic and chemical methods, including 1D, 2D-NMR (1H-1H COSY, HMQC and HMBC) and circular dichroism (CD) experiments. The biosynthesis pathway of salvianolic acid B and salvianolic acid Y (TSL 1) was proposed based on structural analysis. The protection of PC12 cells from injury induced by H2O2 was assessed in vitro using a cell viability assay. Salvianolic acid Y (TSL 1) protected cells from injury by 54.2%, which was significantly higher than salvianolic acid B (35.2%).

Formula optimization of the Jiashitang scar removal ointment and antiinflammatory compounds screening by NF-κB bioactivity-guided dual-luciferase reporter assay system.

Inflammation plays a role in scar formation; therefore, decreasing inflammation benefits scar removal. Jiashitang scar removal ointment (JST) is a commercially available traditional Chinese medicinal formulation. It is composed of extracts from Carthamus tinctorius L. (Car), Rheum officinale Baill. (Rhe), Salvia miltiorrhiza Beg. (Sal), and Panax notoginseng (Burk.) F. H. Chen (Pan), which are all herbs with potent antiinflammatory activities. Our aims are to optimize the formula of JST and to elucidate its antiinflammatory active components. Response surface methodology was applied to optimize proportions of the four herb extracts. The antiinflammatory effects were evaluated using in vitro and in vivo models. To screen for active components in this formula, a bioactivity-based ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry analysis was performed. After optimization, the antiinflammatory effects of the new formula were significantly superior to the original one. Screening identified 13 active ingredients: a series of saffiomin, emodin, salvianolic acid, tanshinone, and triterpenoid saponin derivatives. These active ingredients were predicted to exert nuclear factor-κB inhibiting effects through MAPK, PI3K/AKT, and NIK-IKK pathways. In conclusion, the original formula was successfully optimized with more potent antiinflammatory activity. These methods can be applied to researches of other formulas.

Evaluation of simultaneous nutrient removal and sludge reduction using laboratory scale sequencing batch reactors.

The treatment and disposal of excess sludge has been a rising challenge for wastewater treatment plants worldwide. In this study, simultaneous sludge reduction and nutrient removal was evaluated in laboratory scale sequencing batch reactors (SBRs). Two SBRs were operated alongside for a duration of 370d. One SBR was operated to achieve nutrient removal (control-SBR) at 10d solids retention time (SRT), while the other (modified-SBR) was operated to achieve nutrient removal along with sludge reduction. Sludge reduction in the modified-SBR was accomplished by subjecting the recycled biomass to feasting and fasting at sufficiently high SRT close to infinity (phase I and II) and finite SRT (phase III). The observed biomass yield in the modified-SBR was estimated to be 0.17mg TSSmg(-1) COD, representing 63% sludge reduction compared to the control-SBR. The NH(3) levels in the effluents from both SBRs always remained below detection limit. The average dissolved phosphorus removal efficiencies in the control-SBR and the modified-SBR were 87% and 84%, respectively, during phase II. However, the biomass of the modified-SBR increased during phase II. To control this, biomass wastage was initiated directly from the modified-SBR during phase III at a rate equivalent to the observed biomass accumulation rate in the system in phase II. This resulted in an overall 100d SRT for the modified-SBR system. Following this change, biomass accumulation in the modified-SBR was controlled, and a net 63% sludge reduction could be sustained along with 90% phosphorus and 100% NH3 removal. Consistent denitrification activities were also noticed in both SBRs despite the absence of any carbon source during the anoxic phase of every cycle.