Effect of the Pseudopleuronectes americanus-derived Pleurocidin on DSS-induced Ulcerative colitis in mice and its preliminary molecular mechanisms.

Pleurocidin is an antimicrobial peptide derived from the mucous membranes of the skin or intestinal secretions of Pseudopleuronectes americanus that has antimicrobial and immunomodulatory activities. Ulcerative colitis is recognized as a widespread human disease that may be influenced by environmental and genetic factors. Evidence emphasizes the critical role of the gut microbiota in UC. Synthetic Pleurocidin was analyzed by a combination of liquid chromatography and mass spectrometry. Pleurocidin pharmacological effects were evaluated by DAI score, colon histological score, cytokine levels, and tight junction protein expression in mice. The preliminary molecular mechanism was explored by the levels of key proteins in the NF-κB and MAPK inflammatory signaling pathways in colon tissues. The main analytical methods such as immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blot were used. We then used 16S rRNA gene sequences to characterize the gut microbiota. Firstly, our study demonstrated that rectal injection of Pleurocidin at 5 mg/kg body weight alleviated clinical symptoms and colonic histopathological changes in UC mice caused by DSS. Secondly, Pleurocidin altered the abnormal levels of inflammatory and immune-related cytokines in serum, modulated the significant down-regulation of tight junction proteins, and inhibited the expression of NF-κB and MAPK inflammatory signaling pathway-related proteins. Finally, Pleurocidin can regulate gut microbiota, increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. In conclusion, Pleurocidin alleviates UC symptoms in mice, and its effects on the gut microbiome may be potential pathways. It is providing a promising therapeutic option for UC.

Oral administration of LfcinB alleviates DSS-induced colitis by improving the intestinal barrier and microbiota.

Ulcerative colitis (UC) is a kind of inflammatory bowel disease (IBD) that often recurs and is difficult to cure, and no drugs with few side effects are available to treat this disease. LfcinB is a small molecular peptide obtained by the hydrolysis of bovine lactoferrin in the digestive tract of animals. It has strong antibacterial and anti-inflammatory activities. However, direct evidence that LfcinB improves the condition of colitis in mice is rarely reported. In this study, UC was induced in mice by adding 2.5% dextran sulfate (DSS) to drinking water and LfcinB was orally administered. The results showed that oral administration of LfcinB improved colonic tissue damage and inflammatory cell infiltration, increased the expression of tight junction proteins, and down-regulated the phosphorylation of proteins related to the NF-κB/MAPK inflammatory signalling pathway in mice. It also significantly suppressed the relative abundance of potentially pathogenic bacteria (Bacteroides, Barnesiella and Escherichia) in the intestinal flora. In conclusion, oral administration of LfcinB significantly alleviated DSS-induced UC. This may be related to the regulation of inflammatory signalling pathways and gut microbial composition by LfcinB.

Hemodynamic force dictates endothelial angiogenesis through MIEN1-ERK/MAPK-signaling axis.

It is well-recognized that blood flow at branches and bends of arteries generates disturbed shear stress, which plays a crucial in driving atherosclerosis. Flow-generated fluid shear stress (FSS), as one of the key hemodynamic factors, is appreciated for its critical involvement in regulating angiogenesis to facilitate wound healing and tissue repair. Endothelial cells can directly sense FSS but the mechanobiological mechanism by which they decode different patterns of FSS to trigger angiogenesis remains unclear. In the current study, laminar shear stress (LSS, 15 dyn/cm2) was employed to mimic physiological blood flow, while disturbed shear stress (DSS, ranging from 0.5 ± 4 dyn/cm2) was applied to simulate pathological conditions. The aim was to investigate how these distinct types of blood flow regulated endothelial angiogenesis. Initially, we observed that DSS impaired angiogenesis and downregulated endogenous vascular endothelial growth factor B (VEGFB) expression compared to LSS. We further found that the changes in membrane protein, migration and invasion enhancer 1 (MIEN1) play a role in regulating ERK/MAPK signaling, thereby contributing to endothelial angiogenesis in response to FSS. We also showed the involvement of MIEN1-directed cytoskeleton organization. These findings suggest the significance of shear stress in endothelial angiogenesis, thereby enhancing our understanding of the alterations in angiogenesis that occur during the transition from physiological to pathological blood flow.

The antimicrobial peptide Abaecin alleviates colitis in mice by regulating inflammatory signaling pathways and intestinal microbial composition.

Abaecin is a natural antimicrobial peptide (AMP) rich in proline from bees. It is an important part of the innate humoral immunity of bees and has broad-spectrum antibacterial ability. This study aimed to determine the effect of Abaecin on dextran sulfate sodium (DSS) -induced ulcerative colitis (UC) in mice and to explore its related mechanisms. Twenty-four mice with similar body weight were randomly divided into 4 groups. 2.5% DSS was added to drinking water to induce colitis in mice. Abaecin and PBS were administered rectally on the third, fifth, and seventh days of the experimental period. The results showed that Abaecin significantly alleviated histological damage and intestinal mucosal barrier damage caused by colitis in mice, reduced the concentration of pro-inflammatory cytokines IL-1ß, IL-6, TNF-α, IFN-γ, and the phosphorylation of NF-κB / MAPK inflammatory signaling pathway proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC.

Porcine-derived antimicrobial peptide PR39 alleviates DSS-induced colitis via the NF-κB/MAPK pathway.

PR39 is an antimicrobial peptide (AMP) with a variety of biological functions, including antimicrobial, wound healing, leukocyte chemotaxis, angiogenesis, and immunomodulation; however, its therapeutic efficacy in colitis (IBD) has rarely been reported. For this reason, the present study aimed to investigate the therapeutic effect of PR39 on IBD and its underlying mechanisms. In this experiment, a mouse model of ulcerative colitis (UC) was induced with 3 % dextran sulfate (DSS) and administered by rectal injection of PR39. The results of the study showed that 5 mg/kg of PR39 was able to ameliorate the clinical manifestations of DSS-induced UC mice by improving the clinical symptoms, colonic tissue damage, up-regulating the expression of tight junction proteins, and alleviating the systemic inflammation in mice in various ways. The mechanism of action may involve inhibition of the phosphorylation level of proteins related to the NF-κB/MAPK signaling pathway and modulation of the relative abundance of potentially pathogenic (Bacteroides, Pseudoflavonifractor, Barnesiella, and Oscillibacter) and potentially beneficial bacteria (Candidatus_Saccharibacteria, Desulfovibrio, Saccharibacteria) in the intestinal flora. The results enriched the biological functions of PR-39 and also suggested that PR-39 may be able to be used as a novel drug for the treatment of IBD.

Regulation of the intestinal flora using polysaccharides from Callicarpa nudiflora Hook to alleviate ulcerative colitis and the molecular mechanisms involved.

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that cannot be completely cured by current treatments. C. nudiflora Hook has antibacterial, anti-inflammatory, and hemostatic biological functions; however, the therapeutic role of C. nudiflora Hook or its extracts in IBD remains poorly understood. In this study, we extracted and purified three fractions of C. nudiflora Hook polysaccharides by hydroalcohol precipitation method, which were named as CNLP-1, CNLP-2 and CNLP-3, respectively. CNLP-2, the main component of the polysaccharides of C. nudiflora Hook is an pyranose type acidic polysaccharide composed of Fuc, Rha, Ara, Gal, Glc, Xyl, Man, Gal-UA and Glc-UA, with an Mn of 15.624 kDa; Mw of 31.375 kDa. CNLP-2 was found to have a smooth lamellar structure as observed by scanning electron microscopy. To investigate the effect of CNLP-2 (abbreviated to CNLP) on dextran sodium sulfate (DSS)-induced UC mice and its mechanism of action, we treated DSS-induced UC mice by administering CNLP at a dose of 100 mg/kg every other day. The results of the study showed that CNLP alleviated the clinical symptoms such as body weight (BW) loss, pathological damage, and systemic inflammation. The mechanism may be through the regulation of intestinal flora and its metabolism, which in turn affects the expression of NF-κB/MAPK pathway-related proteins through the metabolites of intestinal flora to further alleviate inflammation and ultimately improve the intestinal barrier function in UC mice. In conclusion, CNLP has great potential for the treatment of IBD.

Impact of anthocyanins derived from Dioscorea alata L. on growth performance, carcass characteristics, antioxidant capacity, and immune function of Hainan black goats.

Dioscorea alata L. anthocyanins (DAC) are natural compounds found in plants and have shown potential health benefits. The objective of this investigation was to assess the impact of anthocyanins sourced from Dioscorea alata L. on the growth, carcass traits, antioxidant potential, and immune response of Hainan black goats. In this study, 30 three-month-old Hainan black goats (with a weight of 11.30 ± 0.82 kg) were selected and randomly divided into two groups, with 15 goats in each group. During the 60-day experiment, the control group (CON) and the treatment group (DAC) were, respectively, supplemented with 0 and 40 mg/kg BW of DAC in the basal diet. The results showed that DAC had no significant impact on the growth performance and body characteristics of Hainan black goats (p > 0.05). However, in terms of meat quality, the addition of DAC significantly increased the pH value and cooking yield 24 h post-slaughter (p < 0.05), while reducing the shear force of the meat (p < 0.05). Compared to the control group, adding DAC to the feed resulted in a significant increase in the total antioxidant capacity (T-AOC) and superoxide dismutase (T-SOD) concentrations in plasma after 30 days of feeding (p < 0.05). After 60 days of feeding, the concentrations of T-AOC, T-SOD, glutathione peroxidase (GSH-Px), and catalase (CAT) in the plasma of the DAC group was higher than that of the control group (p < 0.05), while the concentration of malondialdehyde (MDA) was lower than that of the control group (p < 0.05). In addition, supplementing DAC significantly increased the content of interleukin-10 (IL-10) and immunoglobulin M (IgM) in the plasma of Hainan black goats after 30 days of feeding (p < 0.05), while reducing the content of interleukin-6 (IL-6) (p < 0.05). After 60 days of feeding, the immunoglobulin G (IgG) and IL-10 content in the plasma of the DAC group was significantly increased (p < 0.05), while the concentrations of IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were suppressed (p < 0.05). In summary, these results indicate that supplementing DAC can improve the meat quality, enhance the antioxidant capacity, and immune function of Hainan black goats.

The effect of anthocyanin from Dioscorea alata L. after purification, identification on antioxidant capacity in mice.

Increasing findings devote to searching for natural active compositions as additives to ameliorate health status. Anthocyanin, water-soluble natural pigment, has been concerned due to its favorable antioxidant activity. In this study, we purified anthocyanin from Dioscorea alata L., identified its compounds, and evaluated its antioxidant properties. The results indicated that the purity of anthocyanin increased to 39.59 ± 1.56%, 60.18 ± 1.97%, and 81.08 ± 1.97% after purification via AB-8 macroporous resin, Sep-Pak C18 solid phase, and LH-20 Sephadex stepwise. Ultra-performance liquid chromatography tandem mass spectrometer results indicated that paeoniflorin-3,5-O-dihexoside, petunin-3-O-feruloyl-glucoside-5-O-glucoside, cyanidin-3-O-feruloyl glucoside-5-O-glucoside, cyanidin-3-O-sophoroside, and petunin-3,5-O-dihexoside were the major compounds. The purified anthocyanin exhibited stronger antioxidant activity than the unpurified extract and ascorbic acid, whereas weaker than that of cyanidin-3-O-glucoside in general, which was assessed using DPPH, ABTS, and Fe3+ reducing capacity methods. Moreover, the purified anthocyanin increased GSH-Px, total antioxidant capacity, and superoxide dismutase activities and decreased malondialdehyde concentration on serum in mice after administering lipopolysaccharide for 24 h (p < .05). To summarize, the purified anthocyanin boasts more outstanding antioxidant properties than that of crude extracts. These results provide a reference with source of anthocyanin and it is conducive to use Dioscorea alata L. resources.

Pre-Protection and Mechanism of Crude Extracts from Dioscorea alata L. on H2O2-Induced IPEC-J2 Cells Oxidative Damage.

The purple tubers of Dioscorea alata L. have been found to contain a variety of bioactive chemical components, including anthocyanins, which make it significant to investigate the pre-protective effects of Dioscorea alata L. and its crude extracts on cells prior to oxidative stress. To establish a suitable oxidative damage model, an injured model of IPEC-J2 cells was created using H2O2 as the oxidant. Specifically, when the concentration of H2O2 was 120 µmol/L and the injured time was 8 h, the survival rate of cells decreased to approximately 70%, and the cells exhibited a noticeable oxidative stress reaction. Moreover, the crude extracts of Dioscorea alata L. demonstrated beneficial pre-protective effects on IPEC-J2 cells by increasing the total antioxidant capacity (T-AOC) and catalase (CAT) activities, augmenting the expression of total superoxide dismutase (T-SOD) and its genes, reducing the content of malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-PX) and its expression of genes, and promoting the expression of glucose transporter SGLT1 gene while reducing that of GULT2 gene, thereby facilitating the entry of anthocyanins into cells. In addition, the 50 µg/mL crude extracts effectively inhibited the phosphorylation of IκB and the p65 protein, thus reducing cellular oxidative stress. Given these findings, Dioscorea alata L. can be considered a natural antioxidant for practical breeding and production purposes, with an optimal concentration of crude extracts in this experiment being 50 µg/mL.

The Effect of Anthocyanins from Dioscorea alata L. on Antioxidant Properties of Perinatal Hainan Black Goats and Its Possible Mechanism in the Mammary Gland.

(1) Background: The mammary glands of the perinatal goats are susceptible to reactive oxygen species (ROS) leading to oxidative injury. Although Dioscorea alata L. is rich in anthocyanins with high safety and excellent free-radical-scavenging ability, the effect and mechanism of Dioscorea alata L. anthocyanins (DAC) on the antioxidant capacity of the black Hainan goat has been the subject of few studies to date; (2) Methods: For this reason, feeding experiments were performed by feeding experimental diets, and the pre-protective capacity of DAC on goat mammary epithelial cells was explored on the basis of the established model of H2O2 injury; (3) Results: As well as altering rumen fermentation parameters in perinatal female goats, dietary challenge also improves antioxidant capacity in their blood and milk. thereby enhancing children's antioxidant capacity and increasing their resistance to oxidative stress. However, we also found that DAC pretreatment was capable of activating both Nrf2 and MAPK/JNK pathways, which results in enhanced antioxidase activity and elimination of ROS; (4) Conclusions: Together, these findings suggest that DAC may have a pre-protective role on perinatal Hainan black goats through the regulation of Nrf2 and MAPK/JNK pathways in GMEC.

Nitinol Release of Nickel under Physiological Conditions: Effects of Surface Oxide, pH, Hydrogen Peroxide, and Sodium Hypochlorite.

Nitinol is a nickel-titanium alloy widely used in medical devices for its unique pseudoelastic and shape-memory properties. However, nitinol can release potentially hazardous amounts of nickel, depending on surface manufacturing yielding different oxide thicknesses and compositions. Furthermore, nitinol medical devices can be implanted throughout the body and exposed to extremes in pH and reactive oxygen species (ROS), but few tools exist for evaluating nickel release under such physiological conditions. Even in cardiovascular applications, where nitinol medical devices are relatively common and the blood environment is well understood, there is a lack of information on how local inflammatory conditions after implantation might affect nickel ion release. For this study, nickel release from nitinol wires of different finishes was measured in pH conditions and at ROS concentrations selected to encompass and exceed literature reports of extracellular pH and ROS. Results showed increased nickel release at levels of pH and ROS reported to be physiological, with decreasing pH and increasing concentrations of hydrogen peroxide and NaOCl/HOCl having the greatest effects. The results support the importance of considering the implantation site when designing studies to predict nickel release from nitinol and underscore the value of understanding the chemical milieu at the device-tissue interface.

Temperature dependence of nickel ion release from nitinol medical devices.

Nitinol exhibits unique (thermo)mechanical properties that make it central to the design of many medical devices. However, nitinol nominally contains 50 atomic percent nickel, which if released in sufficient quantities, can lead to adverse health effects. While nickel release from nitinol devices is typically characterized using in vitro immersion tests, these evaluations require lengthy time periods. We have explored elevated temperature as a potential method to expedite this testing. Nickel release was characterized in nitinol materials with surface oxide thickness ranging from 12 to 1564 nm at four different temperatures from 310 to 360 K. We found that for three of the materials with relatively thin oxide layers, ≤ 87 nm nickel release exhibited Arrhenius behavior over the entire temperature range with activation energies of 80 to 85 kJ/mol. Conversely, the fourth ''black-oxide'' material, with a much thicker, complex oxide layer, was not well characterized by an Arrhenius relationship. Power law release profiles were observed in all four materials; however, the exponent from the thin oxide materials was approximately 1/4 compared with 3/4 for the black-oxide material. To illustrate the potential benefit of using elevated temperature to abbreviate nickel release testing, we demonstrated that a > 50 day 310 K release profile could be accurately recovered by testing for less than 1 week at 340 K. However, because the materials explored in this study were limited, additional testing and mechanistic insight are needed to establish a protective temperature scaling that can be applied to all nitinol medical device components.

Hemispheric Asymmetry of Functional Brain Networks under Different Emotions Using EEG Data.

Despite many studies reporting hemispheric asymmetry in the representation and processing of emotions, the essence of the asymmetry remains controversial. Brain network analysis based on electroencephalography (EEG) is a useful biological method to study brain function. Here, EEG data were recorded while participants watched different emotional videos. According to the videos' emotional categories, the data were divided into four categories: high arousal high valence (HAHV), low arousal high valence (LAHV), low arousal low valence (LALV) and high arousal low valence (HALV). The phase lag index as a connectivity index was calculated in theta (4-7 Hz), alpha (8-13 Hz), beta (14-30 Hz) and gamma (31-45 Hz) bands. Hemispheric networks were constructed for each trial, and graph theory was applied to quantify the hemispheric networks' topological properties. Statistical analyses showed significant topological differences in the gamma band. The left hemispheric network showed significantly higher clustering coefficient (Cp), global efficiency (Eg) and local efficiency (Eloc) and lower characteristic path length (Lp) under HAHV emotion. The right hemispheric network showed significantly higher Cp and Eloc and lower Lp under HALV emotion. The results showed that the left hemisphere was dominant for HAHV emotion, while the right hemisphere was dominant for HALV emotion. The research revealed the relationship between emotion and hemispheric asymmetry from the perspective of brain networks.

EEG Functional Connectivity Underlying Emotional Valance and Arousal Using Minimum Spanning Trees.

In recent years, traditional methods such as power spectrum and amplitude analysis have been used to research the emotional electroencephalogram (EEG). The brain network method is also used in emotional EEG research, which can better reflect the activity of brains. A minimum spanning tree (MST) represents the key information flow in the weighted brain network, and it provides a sensitive method to capture subtle information in network organization while effectively avoiding the shortcomings of traditional brain networks. The DEAP dataset provides electroencephalogram (EEG) data for four categories of emotions: high arousal and high valence (HAHV), high arousal and low valence (HALV), low arousal and high valence (LAHV), and low arousal and low valence (LALV). Phase lag index (PLI) weighted matrices were calculated in five frequency bands. On this basis, the minimum spanning trees were constructed. At the same valence level in the gamma (γ) band, HAHV and HALV showed significant higher mean PLI (MPLI), maximum degree (Degreemax) and leaf fraction and significant lower diameter and eccentricity than LAHV and LALV. At the same arousal level in the γ band, HALV showed significant higher MPLI, Degreemax and leaf fraction and significant lower diameter and eccentricity than HAHV. These results indicate that the low-arousal showed more line-shaped configurations than the high-arousal. Additionally, in the high-arousal condition, a shift toward more star-shaped trees from high-valence to low-valence supports the trend toward randomness of the brain network with negative emotions and that the brain is more activated when faced with negative emotions. From a brain network perspective, this phenomenon provides a theoretical basis for negative bias.

The in vitro effect of lipopolysaccharide on proliferation, inflammatory factors and antioxidant enzyme activity in bovine mammary epithelial cells.

Lipopolysaccharide (LPS) was selected as a stimulus to investigate its effect on cell viability and oxidative stress in bovine mammary epithelial cells (BMEC) by detecting the cell relative growth rate (RGR), antioxidant indicators and inflammatory factors. This information was used to provide the theoretical basis for the establishment of a LPS-induced oxidative damage model. The experiment was divided into two parts. The first part used a two-factor experimental design to determine the appropriate incubation time of LPS by detecting the RGR. The third-passage BMEC were divided into 24 groups with six replicates in each group. The first factor was LPS concentration, which was 0 (control), 0.1, 1.0 and 10.0 µg/mL; the second factor was LPS incubation time (2, 4, 6, 8, 12 and 24 h). The optimum LPS incubation time was 6 h according to the results of the first part of the experiment. The second part of the experiment was conducted using a single-factor experimental design, and the third-passage cells were divided into four groups with six replicates in each group. The cells were incubated with culture medium containing different concentrations of LPS (0 [control], 0.1, 1.0 and 10.0 µg/mL) for 6 h to select the appropriate concentration of LPS to measure the antioxidant indicators and inflammatory factors. The results showed the RGR was significantly reduced as the concentration of LPS and the incubation time increased; the interaction between concentration and incubation time was also significant. The cells treated with 0.1 µg/mL of LPS for 6 h had no significant difference in the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) (P > 0.05) compared with the cells in the control group. On the contrary, catalase (CAT) activity and malondialdehyde (MDA) content were markedly lower and higher, respectively, in the 0.1 µg/mL LPS-treated group for 6 h compared with the control group (P < 0.05). The activities of GPx, CAT and SOD in the BMEC treated with 1.0 or 10.0 µg/mL of LPS were significantly lower compared with the cells treated with 0.1 µg/mL of LPS and cells in the control group after 6 h of incubation; however, the opposite trend was detected in MDA content. There was no significant (P > 0.05) difference between the 10.0 and 1.0 µg/mL LPS-treated groups. Compared with the control group, interleukin-1, interleukin-6 and nitric oxide concentrations and the activity of inducible nitric oxide synthase in the 0.1 µg/mL LPS-treated group significantly increased (P < 0.0001), but the levels of tumour necrosis factor did not significantly change (P > 0.05). All of observed indicators were higher in the 1.0 and 10.0 µg/mL LPS-treated groups (P < 0.0001) compared with the other groups, but there was no significant (P > 0.05) difference between the 1.0 and 10.0 µg/mL LPS-treated groups. The results indicated that a concentration of 1.0 µg/mL of LPS and an incubation time of 6 h were the optimum conditions necessary to induce oxidative stress in the BMEC and establish a model for oxidative damage.