Effects of folate-chicory acid liposome on macrophage polarization and TLR4/NF-κB signaling pathway in ulcerative colitis mouse.

BACKGROUND: Chichoric acid (CA) is a major active ingredient found in chicory and Echinacea. As a derivative of caffeic acid, it has various pharmacological effects. PURPOSE: Due to the unclear etiology and disease mechanisms, effective treatment methods for ulcerative colitis (UC) are currently lacking. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and dextran sulfate sodium (DSS)-induced mouse UC models. METHODS: Folate-chicory acid liposome was prepared using the double emulsion ultrasonic method with the aim of targeting folate receptors specifically expressed on macrophages. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and DSS -induced mouse UC models. Furthermore, the effects of the liposomes on macrophage polarization and their underlying mechanisms in UC were explored. RESULTS: The average particle size of folate-chicory acid liposome was 120.4 ± 0.46 nm, with an encapsulation efficiency of 77.32 ± 3.19 %. The folate-chicory acid liposome could alleviate macrophage apoptosis induced by LPS, decrease the expression of inflammatory factors in macrophages, enhance the expression of anti-inflammatory factors, inhibit macrophage polarization towards the M1 phenotype, and mitigate cellular inflammation in vetro. In vivo test, folate-chicory acid liposome could attenuate clinical symptoms, increased colon length, reduced DAI scores, CMDI scores, and alleviated the severity of colonic histopathological damage in UC mice. Furthermore, it inhibited the polarization of macrophages towards the M1 phenotype in the colon and downregulated the TLR4/NF-κB signaling pathway, thereby ameliorating UC in mice. CONCLUSION: Folate-chicory acid liposome exhibited a uniform particle size distribution and high encapsulation efficiency. It effectively treated UC mice by inhibiting the polarization of macrophages towards the M1 phenotype in the colon and downregulating the TLR4/NF-κB signaling pathway.

Enhanced expression of a novel trypsin from Streptomyces fradiae in Komagataella phaffii GS115 through combinational strategies of propeptide engineering and self-degredation sites modification.

This study aimed to enhance the expression level of a novel trypsin gene from Streptomyces fradiae ATCC14544 in Komagataella phaffii GS115 through the combinational use of propeptide engineering and self-degradation residues modification strategies. An artificial propeptide consisted of thioredoxin TrxA, the bovine propeptide DDDDK and the hydrophobic peptide FVEF was introduced to replace the original propeptide while the self-degradation residue sites were predicted and analyzed through alanine screening. The results showed that the quantity and enzymatic activity of asft with engineered propeptide reached 47.02 mg/mL and 33.9 U/mL, which were 9.6 % and 59.29 % higher than those of wild-type (42.9 mg/mL and 13.8 U/mL). Moreover, the introduction of R295A/R315A mutation further enhanced the enzymatic activity (58.86 U/mL) and obviously alleviated the phenomena of self-degradation. The tolerance of trypsin towards alkaline environment was also improved since the optimal pH was shifted from pH 9.0 to pH 9.5 and the half-life value at pH 10 was significantly extended. Finally, the fermentation media composition and condition were optimized and trypsin activity in optimal condition reached 160.58 U/mL, which was 2.73-fold and 11.64-fold of that before optimization or before engineering. The results obtained in this study indicated that the combinational use of propeptide engineering and self-degradation sites modification might have great potential application in production of active trypsins.

Effect of Wu Zhi San supplementation in LPS-induced intestinal inflammation and barrier damage in broilers.

Intestinal inflammation and barrier damage can inhibit the absorption and transportation of nutrients in the small intestine, and lead to various chronic diseases. Wu Zhi San (WZS) is a traditional Chinese formula composed of Schisandrae, Anemarrhenae, Lonicerae, and Glycyrrhizae that was made to cure intestinal inflammation and barrier damage in broilers. To evaluate the protective effect of WZS on intestinal inflammation and barrier damage of broilers under lipopolysaccharide (LPS) stress, a total of 200 one-day-old broilers were randomly divided into five groups, namely, the CON group, LPS group, and three WZS groups (WZS-H, WZS-M, and WZS-L). The groups were designed for stress phase I (days 15, 17, 19, and 21) and stress phase II (days 29, 31, 33, and 35). The protective effect of WZS on the intestinal tract was evaluated by measuring the levels of serum myeloperoxidase (MPO), diamine oxidase (DAO), super oxide dismutase (SOD), and serum D-lactate (D-LA) and the expression of inflammatory factors in jejunum. The results showed that the diet supplemented with WZS could significantly reduce serum MPO, DAO, and D-LA levels and jejunal CD in broilers (p < 0.05), increase serum SOD levels and jejunal VH (p < 0.05), significantly downregulate the expression of NF-κB, TLR4, MyD88, and inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-10), and upregulate Claudin-1, Occludin-1, and ZO-1 in broiler jejunum mucosa (p < 0.05). On the other hand, WZS could significantly reduce the protein expression of NF-κB (p65) in broiler jejunum (p < 0.05). These results indicate that supplementing WZS in the diet can reduce intestinal inflammation and alleviate intestinal barrier damage, and by inhibiting the NF-κB/TLR4/MyD88 signaling pathway, supplementation with WZS intervenes in LPS-induced stress injury in broilers.

Integrative proteomics and metabolomics analysis of non-observable acute effect level PM2.5 induced accumulative effects in AC16 cells.

Chronic exposure to very low ambient PM2.5 has been linked to cardiovascular risks in epidemiological observation, which also brought doubts on its safety threshold. In this study, we approached this question by chronic exposure of AC16 to the non-observable acute effect level (NOAEL) PM2.5 5 µg/mL and its positive reference 50 µg/mL, respectively. The doses were respectively defined on the cell viabilities >95% (p = 0.354) and >90% (p = 0.004) when treated acutely (24 h). To mimic the long-term exposure, AC16 was cultured from the 1st to 30th generations and treated with PM2.5 24 h in every three generations. The integration of proteomic and metabolomic analysis was applied, and 212 proteins and 172 metabolites were significantly altered during the experiments. The NOAEL PM2.5 induced both dose- and time-dependent disruption, which showed the dynamic cellular proteomic response and oxidation accumulation, the main metabolomics changes were ribonucleotide, amino acid, and lipid metabolism that have involved in stressed gene expression, and starving for energy metabolism and lipid oxidation. In summary, these pathways interacted with the monotonically increasing oxidative stress and led to the accumulated damage in AC16 and implied that the safe threshold of PM2.5 may be non-existent when a long-term exposure occurred.

Echinacea purpurea (L.) Moench extract suppresses inflammation by inhibition of C3a/C3aR signaling pathway in TNBS-induced ulcerative colitis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinacea purpurea (L.) Moench (EP) is a perennial herbaceous flowering plant, commonly known as purple conical flower. It was widely used to treat skin inflammation and gastrointestinal diseases. AIM OF STUDY: Ulcerative colitis (UC) is a chronic and nonspecific inflammatory disease. Recent evidence shows that immune disorders are involved in the pathogenesis of UC. To evaluate the protective effect of Echinacea purpurea (L.) Moench exact (EE) on UC and explore the role of complement system in the treatment of UC. MATERIALS AND METHODS: UC model was induced in rats by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and then rats were administered with EE for 10 days. Collect colon tissues for analysis of relevant mechanisms. RESULTS: EE could reduce the weight loss and diarrhea of UC rats. In addition, EE could improve the integrity of intestinal epithelial barrier in UC rats. EE inhibited the level of proinflammatory cytokines and promoted the antioxidation. Furthermore, EE suppressed the expression of C3aR, CFB, CD55, TLR4 and NLRP3. CONCLUSION: These results indicate that EE may achieve therapeutic effect by inhibiting C3a/C3aR signal pathway, suggesting that EE may be used as a medicinal plant to alleviate UC.

Antioxidant activities of sulfated Codonopsis polysaccharides in acute oxidative stress.

This study aimed to explore the protective effect of sulfated Codonopsis polysaccharides (SCP) on acute oxidative stress. SCP was modified by chlorosulfonic acid-pyridine method from Codonopsis polysaccharides (CP), which had 34.48% of sulfate content determined by ultrasonic-acidic barium chromate spectrophotometry. The analysis of Fourier transform-infrared spectroscopy (FT-IR) appeared an absorption peak of SCP at 811.91 cm-1 , which related to C-O-SO3 . In vitro test, the antioxidant activities of CP and SCP was induced by H2 O2 in RAW264.7 cells, results indicated that SCP and CP could significantly enhance the activity of superoxide dismutase (SOD), glutathione peroxidase (GDH-Px) and catalase (CAT), and nitric oxide (NO) and decrease the level of malondialdehyde (MDA), reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) secreted by RAW264.7 cells compared with modeling group (p < .05). The flow cytometry results also revealed that SCP and CP could markedly inhibit the apoptosis of macrophage induced by acute oxidative stress. In vivo test, 50% ethanol was used to induce mice acute oxidative stress, results indicated that the blood biochemical parameters in mice were restored to normal levels following administration of SCP and CP, and alanine aminotransferase (ALT), aspartate transaminase (AST), total protein (TP), albumin (ALB), glucose (GLU), and creatinine (UREA) had significant differences compared with modeling group (p < .05). Quantitative real-time PCR analysis revealed that SCP and CP could promote the expression of Keap1 and Nrf2. In summary, both SCP and CP had protective effects against acute oxidative stress. PRACTICAL APPLICATIONS: Oxidative stress is a kind of stress injury, which can cause a variety of diseases and accelerate physical aging. Codonopsis has many active components, among which Codonopsis polysaccharide has antioxidant effect. Recent studies have found that Codonopsis polysaccharides could be modified by sulfate molecules to obtain higher antioxidant activity. The modified Codonopsis polysaccharides could significantly promote the production of antioxidant enzymes (SOD, CAT, GDH-Px) and reduce the content of oxidative stress marks (ROS, MDA). Moreover, its antioxidant mechanism may be related to the Keap1 /Nrf2 signaling pathway. Therefore, SCP was an effective antioxidant, and could be used as a potential health food with antioxidant and anti-aging effects.

Developing A Case-Based Reasoning Model for Safety Accident Pre-Control and Decision Making in the Construction Industry.

Case-based reasoning (CBR) has been extensively employed in various construction management areas, involving construction cost prediction, duration estimation, risk management, tendering, bidding and procurement. However, there has been a dearth of research integrating CBR with construction safety management for preventing safety accidents. This paper proposes a CBR model which focuses on case retrieval and reuse to provide safety solutions for new problems. It begins with the identification of case problem attribute and solution attribute, the state of hazard is used to describe the problem attribute based on principles of people's unsafe behavior and objective's unsafe state. Frame-based knowledge representation method is adopted to establish the case database from dimensions of slot, facet and facet's value. Besides, cloud graph method is introduced to determine the attribute weight through analyzing the numerical characteristics of expectation value, entropy value and hyper entropy value. Next, thesaurus method is employed to calculate the similarity between cases including word level similarity and sentence level similarity. Principles and procedures have been provided on case revise and case retain. Finally, a real-world case is conducted to illustrate the applicability and effectiveness of the proposed model. Considering the high potential for pre-control and decision-making of construction safety accident, the proposed model is expected to contribute safety managers to take decisions on prevention measures more efficiently.