The proteolytic activity in inflammatory bowel disease: insight from gut microbiota.

Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease caused by the destruction of the intestinal mucosal epithelium that affects a growing number of people worldwide. Although the etiology of IBD is complex and still elucidated, the role of dysbiosis and dysregulated proteolysis is well recognized. Various studies observed altered composition and diversity of gut microbiota, as well as increased proteolytic activity (PA) in serum, plasma, colonic mucosa, and fecal supernatant of IBD compared to healthy individuals. The imbalance of intestinal microecology and intestinal protein hydrolysis were gradually considered to be closely related to IBD. Notably, the pivotal role of intestinal microbiota in maintaining proteolytic balance received increasing attention. In summary, we have speculated a mesmerizing story, regarding the hidden role of PA and microbiota-derived PA hidden in IBD. Most importantly, we provided the diagnosis and therapeutic targets for IBD as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.

Interplay between gut microbiota and bile acids in diarrhoea-predominant irritable bowel syndrome: a review.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that disturbs the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development, affecting more and more people around the world. Despite the multiple factors that account for IBS remaining incompletely studied, emerging evidence demonstrated the abnormal changes in gut microbiota and bile acids (BAs) metabolism closely associated with IBS. Moreover, microbiota drives significant modifications for BAs, consisting of deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, esterification, and so on, while BAs, in turn, affect the microbiota directly or indirectly. In light of the complex connection among gut microbiota, BAs, and IBS, it is urgent to review the latest research progress in this field. In this review, we described the disorders of intestinal microecology and BAs profiles in IBS-D and also highlighted the cross-talk between gut microbiota and BAs in the context of IBS-D. Integrating these, we suggest that new therapeutic strategies targeting the microbiota-BAs axis for IBS-D, even for other related diseases caused by bacteria-bile acid dysbiosis should be expected.

The relationship between gut microbiota and proteolytic activity in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that affects 3.8-9.2% of the world population. It affects the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development. Presently, a large number of studies have shown that compared to healthy individuals, the composition and diversity of gut microbiota in IBS patients have changed, and the proteolytic activity (PA) in fecal supernatant and colonic mucosa of IBS patients has also increased. These findings indicate that the imbalance of intestinal microecology and intestinal protein hydrolysis is closely related to IBS. Furthermore, the intestinal flora is a key substance that regulates the PA and is associated with IBS. The current review described the intestinal microecology and intestinal proteolytic activity of patients with IBS and also discussed the effect of intestinal flora on PA. In summary, this study proposed a pivotal role of gut microbiota and PA in IBS, respectively, and provided an in-depth insight into the diagnosis and treatment targets of IBS as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.

Effect of interfacial composition and crumbliness on aroma release in soy protein/sugar beet pectin mixed emulsion gels.

BACKGROUND: In this study, soy protein isolate/sugar beet pectin (SPI/SBP) emulsion gels were prepared through an enzymatic gelation process. The effects of emulsifier (SBP, SPI or SPI/SBP complex) and emulsification process on the microstructure, texture, breakdown properties and aroma release behavior of resulting emulsion gels were investigated. RESULTS: Oil emulsification by SBP/SPI complex resulted in a higher amount of emulsifier absorbing on the oil-water interface than by SBP and SPI alone, indicating that a more compact interfacial network was formed. Flocculation of oil droplets was observed and corresponding emulsion gels exhibited lower fracture force and strain when the oil was emulsified by SPI and SBP/SPI complex. Moreover, emulsion gels with small droplets produced a greater quantity of small fragments after mastication. However, microstructure did not have a significant effect on breakdown properties of emulsion gels. Headspace gas chromatography analysis showed that the release rate of ethyl butyrate before and after mastication was significantly lower in emulsion gel with more compact network, but the release of aroma compounds with higher hydrophobicity did not show a significant influence of the microstructure and texture of emulsion gel. CONCLUSION: This finding provides a useful application for designing semi-solid foods with desirable flavor perception. © 2016 Society of Chemical Industry.

[Effect of ASO Blood Stasis Syndrome Serum on Vascular Endothelial Cell Injury and Regulation of Taohong Siwu Decoction on it].

OBJECTIVE: To explore the effect of arteriosclerosis obliterans (ASO) blood stasis syndrome (BSS) serum on vascular endothelial cell injury and to study the regulation of Taohong Siwu Decoction (TSD) on it. METHODS: Umbilical vein endothelial cell culture system was established. The serum endothelial cell injury model with ASO BSS was prepared. Low, medium, and high concentrations TSD containing serums were respectively added. The endothelial cell proliferation activity was observed by MTT method. Ultrastructures of endothelial cells were observed under transmission electron microscope. Changes of intracellular calcium ion concentration and the cytoskeleton were observed under laser confocal microscope. Contents of ET, NO, and transforming growth factor beta1 (TGF-beta1) in endothelial cell culture supernatant were detected by ELISA. RESULTS: In ASO BSS serum group endothelial cell proliferation activities decreased, the cell structure was obviously destroyed, calcium ion concentration increased, contents of ET, NO and TGF-beta1 increased significantly (P < 0.01), and ET/NO ratio was imbalanced. After incubating with TSD drug containing serum, endothelial cell proliferation activities and injured cell structures were obviously improved; ET, NO and TGF-beta1 levels decreased (P < 0.05, P < 0.01), ET/NO ratios approximated to the normal level. CONCLUSION: The main mechanism of TSD for treating ASO ASS lied in improving injured vascular endothelial cells and endocrine disorder.

[Chemical constituents from stems of Hedyotis hedyotidea and their immunosuppressive activity].

Hedyotis hedyotidea has been traditionally used for the treatment of arthritis, cold, cough, gastro-enteritis, headstroke, etc. But few studies have screened the active compounds from extracts of H. hedyotidea. In this study, the structure of the chemical constituents from stems of H. hedyotidea were determined and the immunosuppressive activity of the compounds was evaluated. The compounds were separated and purified with silica gel, gel column chromatographies and preparative HPLC, and their structures were identified by spectral methods such as MS and NMR. Eleven compounds were obtained and identified as(6S,9S) -vomifoliol (1), betulonic acid (2), betulinic acid (3), betulin(4), 3-epi-betulinic acid (5), ursolic acid (6), ß-sitosterol (7), stigmast-4-en-3-one (8), 7ß-hydroxysitosterol (9), (3ß,7ß) -7-methoxystigmast-5-en-3-ol (10) and morindacin (11). This is the first report of compounds 1, 2, 4, 8, 9, 10 and 11 from H. hedyotidea. Compounds 1, 2 and 8-11 were firstly isolated from the genus Hedyotis, and compounds 9 and 10 were isolated from the family Rubiaceae for the first time. The immunosuppressive activity of these compounds was tested using the lymphocyte transsormationtest. Compounds 4, 6 and 9 showed significant immunosuppressive activity.

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects more than 3.5 million people, with rising prevalence. It deeply affects patients' daily life, increasing the burden on patients, families, and society. Presently, the etiology of IBD remains incompletely clarified, while emerging evidence has demonstrated that altered gut microbiota and decreased aryl hydrocarbon receptor (AHR) activity are closely associated with IBD. Furthermore, microbial metabolites are capable of AHR activation as AHR ligands, while the AHR, in turn, affects the microbiota through various pathways. In light of the complex connection among gut microbiota, the AHR, and IBD, it is urgent to review the latest research progress in this field. In this review, we describe the role of gut microbiota and AHR activation in IBD and discussed the crosstalk between gut microbiota and the AHR in the context of IBD. Taken as a whole, we propose new therapeutic strategies targeting the AHR-microbiota axis for IBD, even for other related diseases caused by AHR-microbiota dysbiosis.

Efficacy of extracellular vesicles as a cell-free therapy in colitis: a systematic review and meta-analysis of animal studies.

Background: Extracellular vesicles (EVs) mediate inflammation, immune responses, gut barrier integrity, and intestinal homeostasis. Recently, the application of EVs in the treatment of inflammatory bowel disease (IBD) has been under intensive focus. Some studies have been conducted in animal models of colitis, while systematic reviews and meta-analyses are lacking. The current study aimed to conduct a systematic review and meta-analysis of studies investigating the efficacy of EVs on IBD. Methods: A systematic retrieval of all studies in PubMed, EMBASE, MEDLINE, Web of Science, and Cochrane Library reported the effects of EVs in the colitis model up to 22 June 2023. The methodological quality was assessed based on SYRCLE's risk of bias (RoB) tool. Disease activity index (DAI), myeloperoxidase activity (MPO), histopathological score (HS), and inflammatory cytokines (TNF-α, NF-κB, IL-1ß, IL-6, and IL-10) were extracted as analysis indicators by Web Plot Digitizer 4.5. A meta-analysis was performed to calculate the standardized mean difference and 95% confidence interval using random-effect models by Review Manager 5.3 and STATA 14.0 software. Results: A total of 21 studies were included in this meta-analysis. Although the heterogeneity between studies and the potential publication bias limits confidence in the extent of the benefit, EV treatment was superior to the control in the colitis evaluation with reduced DAI, HS, MPO activity, and pro-inflammatory cytokines, including TNF-α, NF-κB, IL-1ß, and IL-6, while increasing the content of anti-inflammatory cytokine IL-10 (all p < 0.05). Conclusion: Our meta-analysis results supported the protective effect of EVs on colitis rodent models based on their potential role in IBD therapy and propelling the field toward clinical studies.

Protein kinase A-mediated 14-3-3 association impedes human Dapper1 to promote dishevelled degradation.

Wnt signaling regulates embryo development and tissue homeostasis, and its deregulation leads to an array of diseases, including cancer. Dapper1 has been shown to be a key negative regulator of Wnt signaling. However, its function and regulation remain poorly understood. In this study, we report that 14-3-3ß interacts with human Dapper1 (hDpr1). The interaction is dependent on protein kinase A (PKA)-mediated phosphorylation of hDpr1 at Ser-237 and Ser-827. 14-3-3ß binding attenuates the ability of hDpr1 to promote Dishevelled (Dvl) degradation, thus enhancing Wnt signaling. We further provide evidence that PKA-mediated Dpr1 phosphorylation may contribute to growth and tumor formation of colon cancer Caco2 cells. Finally, we show that cyclooxygenase-2 expression and PKA activation are positively correlated with Dvl protein levels in colon cancer samples. Together, our findings establish a novel layer of regulation of Wnt signaling by PKA via the 14-3-3-Dpr1-Dvl axis.

[The expressions of periostin and the related factors during healing process of full-thickness cutaneous wound in rat].

OBJECTIVE: To observe the expression of osteoblast-specific factor 2 (periostin, PN), angiopoietin-1 (Ang-1), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 [VEGFR-2/fetal liver kinase-1 (FLK-1)] in wound surface and its peripheral skin, and their effects on wound healing in rats. METHODS: Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups, with 8 rats in each group. An area of 2 cm×2 cm full-thickness skin was excised on both sides of the back of rats. Specimens from wounds were obtained on 1, 4, 7, 10, 14, 21 days after operation, and histological evaluation and immunohistochemical staining of PN, Ang-1, VEGF and FLK-1 were made to determine their expression levels. Normal skin specimens were obtained as normal controls. RESULTS: The expressions of PN, Ang-1, VEGF and FLK-1 were significantly increased in wound surface after operation. Compared with the skin of normal controls, the expression of PN in the tissues of wound increased by 234.4% on the 1st day, and then increased continuously up to 597.9% on the 7th day (reaching the peak) after operation, followed by a decrease, the increase rate was 280.9% on the 21st day, and still remained at a high level (all P < 0.05). The expression of Ang-1 in the tissue of wound increased by 128.1% on the 1st day and 327.5% on the 4th day (reaching the peak), and then, it was gradually decreased. The increase rate was only 80.5% on the 14th day and it rose slightly later (all P < 0.05). The expression of VEGF in the tissues of wound reached the peak (165.8%) on the 7th day. Then it decreased with a slight fluctuation (all P < 0.05). The expression of FLK-1 in the tissues of wound was increased by 56.1% on the 1st day, and the level remained. It reached the peak by an increase of 70.1% on the 7th day (both P < 0.05). Then, it was lowered after the 10th day (all P > 0.05). CONCLUSIONS: The expressions of PN, Ang-1, VEGF, FLK-1 were obviously increased during healing of skin wound, with different peaking time and expressing rates. The increase in expression of PN showed the longest duration and highest peak value. The PN, Ang-1, VEGF, FLK-1 all play a role in the wound healing process, and PN might play an important role during the healing process of a full-thickness cutaneous wound.

A Deep Neural Network-Based Model for Quantitative Evaluation of the Effects of Swimming Training.

This paper analyzes the quantitative assessment model of the swimming training effect based on the deep neural network by constructing a deep neural network model and designing a quantitative assessment model of the swimming training effect. This paper addresses the problem of not considering the influence of the uncertainties existing in the virtual environment when evaluating swimming training and adds the power of the delays in the actual training operation environment, which is used to improve the objectivity and usability of swimming training evaluation results. To better measure the degree of influence of uncertainties, a training evaluation software module is developed to validate the usability of the simulated training evaluation method using simulated case data and compare it with the data after training evaluation using the unimproved evaluation method to verify the correctness and objectivity of the evaluation method in this paper. In the experiments, the feature extractor is a deep neural network, and the classifier is a gradient-boosting decision tree with integrated learning advantages. In the experimental comparison, we can achieve more than 60% accuracy and no more than a 1.00% decrease in recognition rate on DBPNN + GBDT, 78.5% parameter reduction, and 54.5% floating-point reduction on DPBNN. We can effectively reduce 32.1% of video memory occupation. It can be concluded from the experiments that deep neural network models are more effective and easier to obtain relatively accurate experimental results than shallow learning when facing high-dimensional sparse features. At the same time, deep neural networks can also improve the prediction results of external learning models. Therefore, the experimental results of this model are most intuitively accurate when combining deep neural networks with gradient boosting decision trees.

Effect of Bacillus subtilis, Enterococcus faecium, and Enterococcus faecalis supernatants on serotonin transporter expression in cells and tissues.

BACKGROUND: Bacillus subtilis (B. subtilis), Enterococcus faecium (E. faecium), and Enterococcus faecalis (E. faecalis) are probiotics that are widely used in the clinical treatment of irritable bowel syndrome (IBS). Whether the supernatants of these three probiotics can improve gastrointestinal sensation and movement by regulating the serotonin transporter (SERT) expression needs to be clarified. AIM: To investigate whether B. subtilis, E. faecium, and E. faecalis supernatants can upregulate SERT expression in vitro and in vivo. METHODS: Caco-2 and HT-29 cells were stimulated with probiotic culture supernatants for 12 and 24 h, respectively. A male Sprague-Dawley rat model of post-infectious irritable bowel syndrome (PI-IBS) was established and the rats were treated with phosphate-buffered saline (group A) and three probiotics culture supernatants (groups B, C, and D) for 4 wk. The levels of SERT were detected by quantitative PCR and western blotting. RESULTS: The levels of SERT at post-treatment 12 and 24 h were significantly elevated in Caco-2 cells treated with B. subtilis supernatant compared with those in the control group (a P < 0.05). Those levels were markedly upregulated in Caco-2 cells stimulated with E. faecium and E. faecalis supernatants at 24 h (a P < 0.05). In addition, SERT expression in groups B, C, and D was significantly higher than that in group A in the 2nd wk (a P < 0.05). Increased SERT expression was only found in group D in the 3rd wk (a P < 0.05). However, there was no significant difference in SERT expression between the groups in the last week (P > 0.05). CONCLUSION: The supernatants of B. subtilis, E. faecium, and E. faecalis can upregulate SERT expression in intestinal epithelial cells and the intestinal tissues in the rat model of PI-IBS.

Efficacy of combined naikan and morita therapies on psychological distress and posttraumatic growth in Chinese patients with advanced cancer: A randomized controlled trial.

BACKGROUND: Advanced cancer (AC) patients experience serious physical and psychological problems with the disease progression. When approaching the end of life, these patients have to cope with not only the bodily illness, but also the spiritual crisis. Conventional psychological treatments reduce distress to a certain extent, but for patients with AC, especially when they face progressive illness and are approaching death, their psychological problems are complex, and no simple solutions are in sight. Therefore, we designed this study to evaluate the efficacy of the combined Naikan therapy (NT) and Morita therapy (MT) on psychological distress and posttraumatic growth in patients with AC. METHOD: One hundred thirty patients newly diagnosed with AC were allocated randomly into treatment (n = 65) and control (n = 65) groups. Patients in the treatment group received combined NT and MT for 7 consecutive weeks, while the control group received normal medical treatments without NT and MT. Patients were assessed before and after the therapies. The primary outcome measures include distress thermometer (DT) and posttraumatic growth, and the secondary outcome measure contains the list of distress problems. RESULTS: At the post-treatment stage, the treatment group displayed a decreased score of psychological distress as compared to that in the control group, which accompanied by a higher post-traumatic growth total score and subscale scores in relationship to others, new possibilities, personal strength, spiritual changes, and appreciation of life. A significant decrease in fear, sleeping difficulty/insomnia, nervousness/anxiety, and loss of appetite was also observed in the treatment group. CONCLUSION: The results proved that the combined Naikan and Morita therapies decreased the psychological distress and improved the posttraumatic growth of the patients with AC. TRIAL REGISTRATION: ChiCTR1900026691.

Zein based oil-in-glycerol emulgels enriched with ß-carotene as margarine alternatives.

Structuring edible oils into solid lipids without saturated and trans fats has attracted increasing interest due to the benefits for human health and promises potential as novel delivery systems for lipophilic bioactive ingredients. The study shows that a zein stabilized high (ϕ=0.6) oil-in-glycerol (O/G) emulgels enriched with ß-carotene was performed, by a facile one-step homogenization. Rheological measurements and morphologies observations indicated that increasing ß-carotene resulted in a progressive strengthening of gel-like network and improving their spreadability in the O/G emulgels stabilized by zein, which was closely related to the hydrophobic interaction of zein and ß-carotene. The formation of emulgels significantly enhanced the UV photo-stability of ß-carotene, and more than 88% of ß-carotene was retained in 64h storage under UV exposure, and consequently retarded oil oxidation while storage. Further, cakes prepared using zein-based O/G emulgels as a margarine alternative showed comparable functionalities (texture and sensory attributes) to the standard cake.

Subcritical Water Induced Complexation of Soy Protein and Rutin: Improved Interfacial Properties and Emulsion Stability.

Rutin is a common dietary flavonoid with important antioxidant and pharmacological activities. However, its application in the food industry is limited mainly because of its poor water solubility. The subcritical water (SW) treatment provides an efficient technique to solubilize and achieve the enrichment of rutin in soy protein isolate (SPI) by inducing their complexation. The physicochemical, interfacial, and emulsifying properties of the complex were investigated and compared to the mixtures. SW treatment had much enhanced rutin-combined capacity of SPI than that of conventional method, ascribing to the well-contacted for higher water solubility of rutin with stronger collision-induced hydrophobic interactions. Compared to the mixtures of rutin with proteins, the complex exhibited an excellent surface activity and improved the physical and oxidative stability of its stabilized emulsions. This improving effect could be attributed to the targeted accumulation of rutin at the oil-water interface accompanied by the adsorption of SPI resulting in the thicker interfacial layer, as evidenced by higher interfacial protein and rutin concentrations. This study provides a novel strategy for the design and enrichment of nanovehicle providing water-insoluble hydrophobic polyphenols for interfacial delivery in food emulsified systems.

[Variations in expressions of periostin and related factors in early stage of wound healing and scar remodeling in rats].

OBJECTIVE: To investigate the expressions of periostin (PN), angiopoietin-1 (Ang-1), vascular epithelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1) during the processes of scar formation and modulation in rat cutaneous wounds and probe into their roles in wound healing and scaring. METHODS: Eighty-two male Sprague-Dawley (SD) rats were randomly divided into 10 groups with 8-9 rats in each group. Two 2 cm×2 cm full-thickness excisional wounds in the back were created in each rat. The wound surface was observed, and the healing area was measured. The pathological change was observed after hematoxylin and eosin (HE) staining. The expressions of PN, Ang-1, VEGF and Flk-1 in wound surface scar at 4-8 weeks were determined with immunohistochemistry. The expressions of PN, Ang-1 and VEGF were determined by Western blotting. The normal skin was served as control. RESULTS: HE staining showed that the wound surface tissue had healed with epithelization at 4-8 weeks. Immunohistochemistry results showed that there was no significant difference in Flk-1 expression between wound surface tissue and normal skin. The PN expression (A value/µm(2)) in wound surface tissue was significantly lower than that in normal skin at 5 weeks (2.43±0.44 vs. 4.24±0.50, P<0.05), and the expression of Ang-1 and VEGF (A value/µm(2)) at 4, 5, 6, 8 weeks was significantly lower than that in normal skin (Ang-1: 3.51±0.93, 3.10±0.57, 2.77±0.59, 2.77±1.26 vs. 4.89±0.48; VEGF: 1.76±0.68, 1.75±0.49, 1.99±0.42, 1.94±0.86 vs. 4.86±1.63, all P<0.05). In wound surface scar, PN and Flk-1 positive signal was found in cell, and the Ang-1 and VEGF positive signal in extracellular matrix. Western blotting data demonstrated that the expressions of PN, Ang-1 and VEGF peaked at the 10th day after excision with increases to 7.90-22.56 folds compared with normal skin (PN: 2.45±1.51 vs. 0.31±0.19, Ang-1: 18.43±15.20 vs. 1.53±1.42, VEGF: 6.09±4.66 vs. 0.27±0.13, P<0.05 or P<0.01), and then followed with a decrease. CONCLUSIONS: PN, Ang-1, VEGF and Flk-1 are transiently overexpressed in early stage of full-thickness cutaneous wound healing in rats. Their expressions vary in wounds and scars. They participate in the healing of full-thickness cutaneous wounds together and may be essential for the proliferation stage during wound healing.