Caveolin-1 Alleviates Crohn’s Disease–induced Intestinal Fibrosis by Inhibiting Fibroblasts Autophagy Through Modulating Sequestosome 1

Background Intestinal fibrosis is a common complication of Crohn’s disease (CD) and is characterized by the excessive accumulation of extracellular matrix produced by activated myofibroblasts. Caveolin-1 (CAV1) inhibits fibrosis. However, limited data show that CAV1 affects intestinal fibrosis. Methods Human CD tissue samples were gained from patients with CD who underwent surgical resection of the intestine and were defined as stenotic or nonstenotic areas. A dextran sodium sulfate–induced mouse model of intestinal fibrosis was established. For in vitro experiments, we purchased CCD-18Co intestinal fibrosis cells and isolated and cultured human primary colonic fibroblasts. These fibroblasts were activated by transforming growth factor β administration for 48 hours. In the functional experiments, a specific small interfering RNA or overexpression plasmid was transfected into fibroblasts. The messenger RNA levels of fibrosis markers, such as α-smooth muscle actin, fibronectin, connective tissue growth factor, and collagen I1α, were determined using quantitative polymerase chain reaction. Western blot analysis was applied to detect the expression of CAV1, SQSTM1/p62 (sequestosome 1), and other fibrosis markers. Results In human CD samples and the dextran sodium sulfate–induced mouse model of intestinal fibrosis, we observed a downregulation of CAV1 in fibrosis-activated areas. Mechanistically, CAV1 knockdown in both human primary colonic fibroblasts and CCD-18Co cells promoted fibroblast activation, while CAV1 overexpression inhibited fibroblast activation in vitro. We found that SQSTM1/p62 positively correlated with CAV1 expression levels in patients with CD and that it was indirectly modulated by CAV1 expression. Rescue experiments showed that CAV1 decreased primary human intestinal fibroblast activation by inhibiting fibroblast autophagy through the modulation of SQSTM1/p62. Conclusions Our data demonstrate that CAV1 deficiency induces fibroblast activation by indirectly regulating SQSTM1/p62 to promote fibroblast autophagy. CAV1 or SQSTM1/p62 may be potential therapeutic targets for intestinal fibrosis.

Facilitation of colonic T cell immune responses is associated with an exacerbation of dextran sodium sulfate–induced colitis in mice lacking microsomal prostaglandin E synthase-1

Background Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that acts downstream of cyclooxygenase and plays a major role in inflammation by converting prostaglandin (PG) H2 to PGE2. The present study investigated the effect of genetic deletion of mPGES-1 on the development of immunologic responses to experimental colitis induced by dextran sodium sulfate (DSS), a well-established model of inflammatory bowel disease (IBD). Methods Colitis was induced in mice lacking mPGES-1 (mPGES-1−/− mice) and wild-type (WT) mice by administering DSS for 7 days. Colitis was assessed by body weight loss, diarrhea, fecal bleeding, and histological features. The colonic expression of mPGES-1 was determined by real-time PCR, western blotting, and immunohistochemistry. The impact of mPGES-1 deficiency on T cell immunity was determined by flow cytometry and T cell depletion in vivo. Results After administration of DSS, mPGES-1−/− mice exhibited more severe weight loss, diarrhea, and fecal bleeding than WT mice. Histological analysis further showed significant exacerbation of colonic inflammation in mPGES-1−/− mice. In WT mice, the colonic expression of mPGES-1 was highly induced on both mRNA and protein levels and colonic PGE2 increased significantly after DSS administration. Additionally, mPGES-1 protein was localized in the colonic mucosal epithelium and infiltrated inflammatory cells in underlying connective tissues and the lamina propria. The abnormalities consistent with colitis in mPGES-1−/− mice were associated with higher expression of colonic T-helper (Th)17 and Th1 cytokines, including interleukin 17A and interferon-γ. Furthermore, lack of mPGES-1 increased the numbers of Th17 and Th1 cells in the lamina propria mononuclear cells within the colon, even though the number of suppressive regulatory T cells also increased. CD4+ T cell depletion effectively reduced symptoms of colitis as well as colonic expression of Th17 and Th1 cytokines in mPGES-1−/− mice, suggesting the requirement of CD4+ T cells in the exacerbation of DSS-induced colitis under mPGES-1 deficiency. Conclusions These results demonstrate that mPGES-1 is the main enzyme responsible for colonic PGE2 production and deficiency of mPGES-1 facilitates the development of colitis by affecting the development of colonic T cell–mediated immunity. mPGES-1 might therefore impact both the intestinal inflammation and T cell–mediated immunity associated with IBD.

Interphase distribution of a number of polybasic carboxylic acids in aqueous two-phase systems based on polyethylene glycol-1500

In this work, we studied the interphase distribution of a number of polybasic carboxylic acids, in particular, malic, succinic, glutaric, citric, ascorbic and tartaric in two-phase aqueous systems polyethylene glycol-1500 (PEG-1500) - sodium sulfate - water and PEG-1500 - ammonium sulfate - water. Using the spectrophotometric method of analysis, quantitative characteristics (interfacial distribution and degree of recovery) of the extraction of carboxylic acids were determined. In conclusion, it was found that the considered two-phase aqueous systems are promising in the process of extraction of polybasic carboxylic acids. In particular, the system polyethylene glycol 1500 - sodium sulfate - water has effective extraction properties for succinic malic and ascorbic acids. On the other hand, depending on the composition of the extraction systems, the quantitative characteristics for citric, glutaric and tartaric acids practically do not differ.

Reproductive Ability of Doe-Rabbits and Growth and Preservation of the Offspring by Feeding Sulfur Compounds

The use of organic minerals in the form of nanocompounds as a substitute for mineral inorganic salts is promising, but insufficiently studied. Therefore, the purpose of the search was to determine the influence of drinking sulfur citrate and sodium sulfate 14 days before insemination and up to 20th day of lactation on the reproductive capacity of rabbits and the preservation of the offspring up to 40th day of life. The research was carried out on rabbits of the second breed of Hyla breed in “Horlytsia”. Сontrol group were fed without restriction complete ration granular feed with free access to water. 1st experimental group were fed with the ration of the control group and during the day were watered with sulfur citrate, at the rate of 8 μg S/kg of body weight. II experimental group were fed with the ration of the control group and with water was given sodium sulfate in the amount of 40 mg S/kg of body weight. Additives to rabbits were watered 14 days before insemination and for up to 20 days of lactation. It was found that on the first day of life of young rabbits their number in the I and II experimental groups was respectively higher by 8.5 and 4.2% compared to the control. The number of young rabbits at 20 and 40 days of age in the I and II experimental groups was respectively higher by 10.4 and 4.4% and 14.0 and 4.6% compared to the control group. The weight of rabbits in the nest of the II experimental group at 1, 20 and 40 days of life was respectively higher by 2.8; 6.1 and 7.0%, which is based on the average mass of one rabbit for these periods and amounted to 1.1, respectively; 2.7 and 4.3% compared with animals in the control group. The average amount of milk produced by rabbits of I and II experimental groups was respectively higher by 10.2% and 6.6% per day and for 20 days of the lactation period compared to the control. The preservation of rabbits in the I and II experimental groups was respectively higher by 6.4 and 6.4% and 3.6 and 4.4% at 20 and 40 days of life of young rabbits compared to the control group. The results of the research indicate the possibility of additional use in the ration of rabbits of the addition of sulfur citrate in the amount of 8 μg S/kg of body weight to increase metabolism and reproductive capacity during periods of increased physiological load

Durability of Mortars with Fly Ash Subject to Freezing and Thawing Cycles and Sulfate Attack

Destruction of cement composites occurs due to the alternate or simultaneous effects of aggressive media, resulting in the destruction of concrete under the influence of chemical and physical factors. This article presents the results of changes in the measurement of linear strains of samples and changes in the microstructure of cement after 30 freezing and thawing cycles and immersed in 5% sodium sulfate solution. The compressive strengths ratios were carried out at the moment when the samples were moved to the sulfate solution after 30 cycles and at the end of the study when the samples showed visual signs of damage caused by the effect of 5% Na2SO4. The composition of the mixtures was selected based on the Gibbs triangle covering the area up to 40% replacement of Portland cement with low and high-calcium fly ashes or their mixture. Air-entrained and non-air entrained mortars were made of OPC, in which 20%, 26.6%, and 40% of Portland cement were replaced with low and/or high-calcium fly ash. Initial, freezing and thawing cycles accelerated the destruction of non- air-entrained cement mortars immersed in 5% sodium sulfate solution. The sulfate resistance, after the preceding frost damage, decreased along with the increase in the amount of replaced fly ash in the binder. Air-entrained mortars in which 20% of cement was replaced with high-calcium fly ash showed the best resistance to the action of sodium sulfate after 30 freezing and thawing cycles.

Saccharina japonica Ethanol Extract Ameliorates Depression/Anxiety-Like Behavior by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Dextran Sodium Sulfate Induced Ulcerative Colitis Mice

Saccharina japonica is a common marine vegetable in East Asian markets and has a variety of health benefits. This study was focused on the anti-depressant/anxiety effects of Saccharina japonica ethanol extract (SJE) on dextran sodium sulfate (DSS)-induced mice and its potential mechanism in their brain. Male C57BL/6 mice were treated with mesalazine and various doses of SJE (1, 2, and 4 g/kg body weight) for 2 weeks, followed by DSS treatment at the second week. The DSS-induced mice showed depression/anxiety-like behavior, which included shorter path length in the open field test and longer immobility time in the tail suspension test. L-SJE alleviated the depression-like behaviors. In the DSS-induced mice, reduced synaptic plasticity activated microglia, increased proinflammatory cytokines, decreased anti-inflammatory cytokine, and increased expression levels of Toll-like receptors-4, nuclear factor kappa-B, NOD-like receptors 3, apoptosis-associated speck-like protein, and Caspase-1 were observed, most of which were alleviated by SJE treatment. Furthermore, all the SJE groups could significantly enhance superoxide dismutase activity, while the L-SJE treatment decreased the contents of malondialdehyde, and the H-SJE treatment inhibited apoptosis. All these results showed that the SJE might serve as a nutritional agent for protecting the brain in ulcerative colitis mice.

The Effects of Sishen Wan on T Cell Responses in Mice Models of Ulcerative Colitis Induced by Dextran Sodium Sulfate

Currently, it is unclear whether Sishen Wan (SSW) could modulate the balance of Th1 cells, Th17 cells, and Tregs and we evaluated the effects of SSW on T cell responses in mice models of ulcerative colitis (UC). The mice models of acute UC (4% dextran sodium sulfate (DSS), 8 days) and chronic UC (3% DSS, 16 days) with SSW were assayed. Colon tissues were collected for immunohistochemical analysis, enzyme linked immunosorbent assay (ELISA), and flow cytometry (FCM). The expressions of cytokines associated with Tregs, transcription factors of Th17 cells, the frequencies of Th1 cells, Th17 cells, and Tregs, and the functional plasticity of Th17 cells were detected. The frequency of IFN-γ+ T cells was not changed significantly with SSW treatment in acute DSS. In chronic models, the frequency of IFN-γ+ T cells was downregulated with SSW. Meanwhile, the levels of RORγt and the frequency of IL-17A+ Th17 cells showed no significant differences after SSW treatment. Despite no significant effect on the transdifferentiation of Th17 cells in chronic UC models, SSW transdifferentiated Th17 cells into IL-10+ Th17 cells and downregulated IFN-γ+ Th17 cells/IL-10+ Th17 cells in acute DSS. Moreover, there were no significant changes of cytokines secreted by Tregs in acute DSS after SSW treatment, but SSW facilitated the expressions of IL-10 and IL-35, as well as development of IL-10+ Tregs in chronic DSS. SSW showed depressive effects on the immunoreaction of Th17 cells and might promote the conversion of Th17 cells into IL-10+ Th17 cells in acute UC, while it inhibited the excessive reaction of Th1 cells, facilitated the development of Tregs, and enhanced the anti-inflammatory effects in chronic UC.

Alkali-Activated Hybrid Cements Based on Fly Ash and Construction and Demolition Wastes Using Sodium Sulfate and Sodium Carbonate

This article demonstrates the possibility of producing alkali-activated hybrid cements based on fly ash (FA), and construction and demolition wastes (concrete waste, COW; ceramic waste, CEW; and masonry waste, MAW) using sodium sulfate (Na2SO4) (2–6%) and sodium carbonate (Na2CO3) (5–10%) as activators. From a mixture of COW, CEW, and MAW in equal proportions (33.33%), a new precursor called CDW was generated. The precursors were mixed with ordinary Portland cement (OPC) (10–30%). Curing of the materials was performed at room temperature (25 °C). The hybrid cements activated with Na2SO4 reached compressive strengths of up to 31 MPa at 28 days of curing, and the hybrid cements activated with Na2CO3 yielded compressive strengths of up to 22 MPa. Based on their mechanical performance, the optimal mixtures were selected: FA/30OPC-4%Na2SO4, CDW/30OPC-4%Na2SO4, FA/30OPC-10%Na2CO3, and CDW/30OPC-10%Na2CO3. At prolonged ages (180 days), these mixtures reached compressive strength values similar to those reported for pastes based on 100% OPC. A notable advantage is the reduction of the heat of the reaction, which can be reduced by up to 10 times relative to that reported for the hydration of Portland cement. These results show the feasibility of manufacturing alkaline-activated hybrid cements using alternative activators with a lower environmental impact.

The Equilibrium Time and Salt Expansion Characteristic of Sulfate Saline Soil upon Cooling

The salt expansion disease is severe for the soil containing sodium sulfate in cold regions. This paper carried out one-dimensional salt expansion tests of saline soil, the crystallization test of saturated sodium sulfate solution, and the numerical cooling tests to explore the stability time of the salt expansion test and determine the standard procedure of salt expansion tests. The test results demonstrate that (i) the temperature equilibrium and the crystallization process are almost simultaneously completed in both sulfate saline soil and sulfate solution upon cooling; (ii) referring to the deformation equilibrium standard used in soil consolidation test, an expansion rate of less than 0.02 mm/h is suggested in the saline expansion test; and (iii) the equilibrium time is found to have a quadratic polynomial relationship to sample size and is much shorter under liquid bath conditions than under gas bath conditions. Based on these findings, a standard procedure of the one-dimensional salt expansion test is proposed, in which the test equipment, the test process, the deformation stabilization time of salt expansion, and the data processing method are provided. As the deformation and the temperature are synchronized, the deformation stabilization time of samples with different sizes in different cooling media is recommended.