Sodium Sulfate Research Articles

A comprehensive study of melt foaming in E‐glass batch‐to‐melt conversion process: Effects of sulfate content and chemistry of raw materials

AbstractControl of sulfate‐induced melt fining without excessive foaming is one of the critical steps in maintaining the stability of E‐glass fiber manufacturing processes. Besides, the efficiency of combustion or energy utilization is directly affected by the extent of the melt‐foaming. A fundamental understanding of key factors affecting melt foaming under the simulated oxy‐fuel combustion environment will enable commercial E‐glass fiber production to optimize both batch chemistry and operation conditions to achieve adequate furnace control. In this study, six types of E‐glass batches with the same target glass composition were prepared by using four different CaO sources; calcined limes with different SO3 contents, limestone, limestone with sodium sulfate, and a mixture of limestone and calcined lime. All batch samples were examined by HTMOS‐EGA system (high temperature melting observation system with evolved gas analysis). HTMOS enables monitoring batch‐to‐melt conversation steps by using a high‐resolution camera and EGA detects the evolved reaction gaseous, such as CO, CO2, and SO2 via an Fourier transform infrared (FTIR) gas analyzer. Gases of water vapor, N2, and O2 were introduced accordingly into the fused quartz crucible to simulate similar oxy‐fuel atmosphere of the furnace operation. This study aimed to investigate the effects of different SO3 contents in batches and different raw material chemistries on the foam formation in E‐glass melts under the oxy‐fuel atmosphere. Different raw materials were characterized by mineralogical analysis, chemical analysis, particle size distribution, chemical oxygen demanding (COD) level, and Brunauer–Emmett–Teller (BET) analysis. Although some of the batches contained the same SO3 content, different foam formations resulted from the effect of the batch chemistry. Our detailed HTMOS‐EGA investigations show that not only SO3 content in the batch affects foam formation in E‐glass melts, but also raw material chemistry and particle size have strong effects on the melt foaming in E‐glass batch melting, especially for those of ingredients having hydroxide phases and/or finer particles with higher specific areas.

Oral Administration of PLGA Nanoparticles to Deliver Antisense Oligonucleotides to Inflammatory Lesions in the Gastrointestinal Tract.

In this study, we prepared antisense oligonucleotide (ASO)-encapsulated nanoparticles (NPs) with a suitable profile for oral administration for the treatment of inflammatory bowel disease (IBD). We chose a water-in-oil-in-water (w/o/w) method to prepare the NPs using poly(lactide-co-glycolide) as a matrix and Pluronic as a stabilizer. The obtained NPs had a suitable diameter (158 nm) for the penetration of the mucus layer, endocytic uptake by enterocytes, and accumulation in inflammatory lesions in the intestine. The amount of ASOs in the NPs was relatively large (6.41% (w/w)). When the NPs were stably dispersed in solutions that mimicked gastrointestinal (GI) juice, minimal leakage of ASOs was demonstrated over the required period. The NPs were administered orally to mice with colitis induced by dextran sodium sulfate, which reduced target gene expression in the colons and rectums of the mice, whereas naked ASO administration caused no reduction in gene expression. Thus, the NPs have the potential of promising oral carriers of ASOs for the treatment of IBD that specifically target inflammatory lesions in the GI tract, thereby reducing the non-specific toxic effects of ASOs.

Assessing the effects of Na2SO4 and NaCl on the properties of geopolymer concrete subjected to elevated temperatures

AbstractSince concrete is exposed to chemical, mechanical, or physical deteriorating effects simultaneously or successively under environmental conditions, this study focused on the durability of geopolymer concretes containing ground blast furnace slag (GGBFS) and fly ash (FA) under the effects of sulfate and salt after elevated temperatures. For this aim, five FA‐based geopolymer concrete mixtures with different GGBFS contents were produced and cured at 90°C for 72 h. First, the produced samples were exposed to 200, 400, 600, and 800°C for 2 h. Then, the samples were put into 5% sodium sulfate (Na2SO4) and 5% sodium chloride (NaCl) solutions for 30 days. The impacts of elevated temperature + Na2SO4 and elevated temperature + NaCl on geopolymer concrete were investigated by compressive strength, mass loss, visual examination, capillary water absorption, x‐ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT‐IR). As a result, although cracking or strength decreases in concrete have been observed after only elevated temperatures, it has exhibited significant resistance to the integrated deterioration influences, has not disintegrated, and maintained its integrity under appropriate mix design and curing conditions. Shortly, the results demonstrated the ability of geopolymer concrete subjected to elevated temperatures with acceptable strength and durability under chemical effects, even if left for a short time.

Inhibition of Immunoproteasome Attenuates NLRP3 Inflammasome Response by Regulating E3 Ubiquitin Ligase TRIM31

Excessive secretion of pro-inflammatory cytokines leads to the disruption of intestinal barrier in inflammatory bowel disease (IBD). The inflammatory cytokine tumor necrosis factor alpha (TNFα) induces the assembly of the NLRP3 inflammasome, resulting in the augmented secretion of inflammatory cytokines implicated in the pathogenesis of inflammatory bowel disease (IBD). TNFα has also been known to induce the formation of immunoproteasome (IP), which incorporates immunosubunits LMP2, LMP7, and MECL-1. Inhibition of IP activity using the IP subunit LMP2-specific inhibitor YU102, a peptide epoxyketone, decreased the protein levels of NLRP3 and increased the K48-linked polyubiquitination levels of NLRP3 in TNFα-stimulated intestinal epithelial cells. We observed that inhibition of IP activity caused an increase in the protein level of the ubiquitin E3 ligase, tripartite motif-containing protein 31 (TRIM31). TRIM31 facilitated K48-linked polyubiquitination and proteasomal degradation of NLRP3 with an enhanced interaction between NLRP3 and TRIM31 in intestinal epithelial cells. In addition, IP inhibition using YU102 ameliorated the symptoms of colitis in the model mice inflicted with dextran sodium sulfate (DSS). Administration of YU102 in the DSS-treated colitis model mice caused suppression of the NLRP3 protein levels and accompanied inflammatory cytokine release in the intestinal epithelium. Taken together, we demonstrated that inhibiting IP under inflammatory conditions induces E3 ligase TRIM31-mediated NLRP3 degradation, leading to attenuation of the NLRP3 inflammatory response that triggers disruption of intestinal barrier.

Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention

Colorectal cancer stands as the third most prevalent form of cancer worldwide, with a notable increase in incidence in Western countries, mainly attributable to unhealthy dietary habits and other factors, such as smoking or reduced physical activity. Greater consumption of vegetables and fruits has been associated with a lower incidence of colorectal cancer, which is attributed to their high content of fiber and bioactive compounds, such as flavonoids. In this study, we have tested the flavonoids quercetin, luteolin, and xanthohumol as potential antitumor agents in an animal model of colorectal cancer induced by azoxymethane and dodecyl sodium sulphate. Forty rats were divided into four cohorts: Cohort 1 (control cohort), Cohort 2 (quercetin cohort), Cohort 3 (luteolin cohort), and Cohort 4 (xanthohumol cohort). These flavonoids were administered intraperitoneally to evaluate their antitumor potential as pharmaceutical agents. At the end of the experiment, after euthanasia, different physical parameters and the intestinal microbiota populations were analyzed. Luteolin was effective in significantly reducing the number of tumors compared to the control cohort. Furthermore, the main significant differences at the microbiota level were observed between the control cohort and the cohort treated with luteolin, which experienced a significant reduction in the abundance of genera associated with disease or inflammatory conditions, such as Clostridia UCG-014 or Turicibacter. On the other hand, genera associated with a healthy state, such as Muribaculum, showed a significant increase in the luteolin cohort. These results underline the anti-colorectal cancer potential of luteolin, manifested through a modulation of the intestinal microbiota and a reduction in the number of tumors.

H2 Reduction of Na2SO4 to Na2S Based on Dilute-Phase Fluidization

Sodium sulfate (Na2SO4) is used in the ecofriendly production of sodium sulfide (Na2S) through H2 reduction, thereby facilitating the valorization of Na2SO4. However, studies on this technique remain at the laboratory stage. This paper proposes a novel process involving the external circulation of Na2S in a dilute-phase fluidized system to address the low-temperature eutectic formation between Na2S and Na2SO4 during the H2 reduction of Na2SO4 to Na2S. The process aims to increase the reaction temperature of the Na2SO4 while reducing the volume of the liquid phase formed to prevent sintering blockages and enhance the reduction rate. In a proprietary experimental setup, the H2 reduction process in a dilute-phase fluidized system was investigated. The Na2S/Na2SO4 ratio and reaction temperature were determined to be critical factors influencing the Na2SO4 reduction rate. The melting point of the system increased and the amount of liquid phase produced decreased as the Na2S content was increased to more than 60%. The Na2S–Na2SO4 mixture (mass ratio of 80:20) existed as a solid at the reaction temperature of 740 °C. After roasting for 10 s, the Na2SO4 reduction rate reached 93.7% and the Na2S content in the mixture increased to 98.74%.

Myeloperoxidase Gene Deletion Causes Drastic Microbiome Shifts in Mice and Does Not Mitigate Dextran Sodium Sulphate-Induced Colitis

Neutrophil-myeloperoxidase (MPO) is a heme-containing peroxidase which produces excess amounts of hypochlorous acid during inflammation. While pharmacological MPO inhibition mitigates all indices of experimental colitis, no studies have corroborated the role of MPO using knockout (KO) models. Therefore, we investigated MPO deficient mice in a murine model of colitis. Wild type (Wt) and MPO-deficient mice were treated with dextran sodium sulphate (DSS) in a chronic model of experimental colitis with three acute cycles of DSS-induced colitis over 63 days, emulating IBD relapse and remission cycles. Mice were immunologically profiled at the gut muscoa and the faecal microbiome was assessed via 16S rRNA amplicon sequencing. Contrary to previous pharmacological antagonist studies targeting MPO, MPO-deficient mice showed no protection from experimental colitis during cyclical DSS-challenge. We are the first to report drastic faecal microbiota shifts in MPO-deficient mice, showing a significantly different microbiome profile on Day 1 of treatment, with a similar shift and distinction on Day 29 (half-way point), via qualitative and quantitative descriptions of phylogenetic distances. Herein, we provide the first evidence of substantial microbiome shifts in MPO-deficiency, which may influence disease progression. Our findings have significant implications for the utility of MPO-KO mice in investigating disease models.

THE CHEMICAL ORIGIN AND GEOTHERMOMETERY OF HOT SPRINGS WATERS IN THE REGION OF KHENCHELA, ALGERIA

Our study is carried out on the trio of thermomineral waters in the region of Khenchela - Hammam Salhin, Hammam Knif, and Hammam Djaarir - Northeast of Algeria. The purpose of this study is to determine the physicochemical and geothermal origin of the thermal spring (temperature, pH, and electrical conductivity). The temperatures of the thermal water samples which were being studied varied from 38 to 72°C; therefore, this variation has a direct relation to the climatic conditions and/or the combination of the water which is derived from various sources in the formation of the thermal spring. Additionally, the pH value of the spring under study is of a neutral to slightly alkaline quality, while its electric conductivities are high, ranging from 3059 μS/Cm to 5007 μS/Cm. The Piper diagrams presented the domination of sodium chloride (Na-Cl) and sodium sulfate (Na-SO4) facies as two types of water in the hydrochemical facies. These facies indicate the mineral composition of the thermal waters, a product from the reservoir by way of geological formations in the subsurface. This is a plausible reason from the chemical changes observed in the fluids and can well be associated with the high influence of water-rock interaction, that is, the formation of sodium bicarbonate water to sodium-chlorinated water formation, where it is linked with the effects of dissolution and salinity in the formation of saliva found in regions with semi-arid climatic conditions. Evaporation would play a major role in increasing the sodium content, while the IIRG plots closer to the industry "α" standard than the other plots. These are the characteristic features of an evaporation-based system. The crucial parameter C serves as a strong indicator of circulation in carbonate reservoirs subject to evaporation.

Sulphate resistance of low-clinker engineered cementitious composites examined by MicroXRF imaging.

Engineered cementitious composites (ECC) are a class of high-performing fibre-reinforced cementitious materials recognised for their increased ductility and durability compared to conventional cement-based materials, owing to their autogenously controlled tight crack widths, even when subjected to high strains. To reduce ECC's environmental impact, this research examines the use of a low-clinker binder - limestone-calcined clay cement (LC3) - as an alternative to portland cement (PC), along with fly ash to further reduce the clinker proportion and the embodied CO2 of the formulations. In conventional concrete, LC3 hydrates to a denser microstructure resulting from the synergistic reaction between limestone and calcined clay. At the lower water contents typical of ECC and with the presence of fly ash, the influence of the binder composition on the microstructure is difficult to anticipate. To examine the influence of these compositional variables on microstructure, permeability and durability, the sulphate resistance of LC3-based ECC is explored. Specifically, the ECC-LC3 blends are designed with high clinker replacement rate of 75% by mass of binder and contain either conventional fly ash or reclaimed fly ash at 50% by mass of binder. Expansion of ECC-LC3 samples subjected to standard sodium sulphate test conditions was measured up to 12 months and the depth of penetration of sulphates into the ECC-LC3 of varying compositions was quantified using micro-X-Ray Fluorescence (microXRF) imaging and modelling. The expansion results show that the ECC-LC3 formulations performed better than the PC samples and can provide adequate resistance to external sulphate attack, even when reclaimed fly ashes are used in place of the conventional ash. In addition, the shallow penetration of sulphate into these cementitious composites demonstrates the low diffusion coefficients values that were determined using the quantitative data from MicroXRF imaging.

Nanoscale Stabilization Mechanism of Sodium Sulfate Decahydrate at Polyelectrolyte Interfaces

Nanoscale Stabilization Mechanism of Sodium Sulfate Decahydrate at Polyelectrolyte Interfaces

Milk and Lacticaseibacillus casei BL23 effects on intestinal responses in a murine model of colitis.

Probiotic-containing fermented dairy foods have the potential to benefit human health, but the importance of the dairy matrix for efficacy remains unclear. We investigated the capacity of Lacticaseibacillus casei BL23 in phosphate-buffered saline (BL23-PBS), BL23-fermented milk (BL23-milk), and milk to modify intestinal and behavioral responses in a Dextran Sodium Sulfate (DSS, 3% w/v) mouse model of colitis. Significant sex-dependent differences were found such that female mice exhibited more severe colitis, greater weight loss, and higher mortality rates. Sex differences were also found for ion transport ex vivo, colonic cytokine and tight junction gene expression, and fecal microbiota composition. Measurements of milk and BL23 effects showed BL23-PBS consumption improved weight recovery in females, while milk resulted in better body weight recovery in males. Occludin and Claudin-2 gene transcript levels indicated barrier function was impaired in males, but BL23-milk was still found to improve colonic ion transport in those mice. Pro-inflammatory and anti-inflammatory gene expression levels were increased in both male and female mice fed BL23, and to a more variable extent, milk, compared to controls. The female mouse fecal microbiota contained high proportions of Akkermansia (average of 18.1%) at baseline, and females exhibited more changes in gut microbiota composition following BL23 and milk intake. Male fecal microbiota harbored significantly more Parasutterella and less Blautia and Roseburia after DSS treatment, independent of BL23 or milk consumption. These findings show the complex interplay between dietary components and sex-dependent responses in mitigating inflammation in the digestive tract.

The effect of novel paraprobiotic cocktail on dextran sodium sulfate induced acute colitis control focusing on autophagy signaling pathway.

Paraprobiotics are a non-viable form of probiotics that are reported to provide significant health benefits. Nevertheless, little is known about the beneficial effects of paraprobiotics on inflammatory bowel disease. Although probiotics show potential as therapeutic agents for a range of diseases, including inflammatory bowel disease (IBD), there are certain risks associated with their use. These risks include toxin production, hemolytic potential, antibiotic resistance, and the need to analyze metabolic activities. Hence Using paraprobiotic with the lower aforementioned risk would therefore be the preferable option. Here, we conducted an in vivo study to evaluate the preventive effect of our native paraprobiotic cocktail against dextran sulfate sodium (DSS)-induced murine colitis by affecting the autophagy signaling pathway. Four-week-old male C57Bl/6 mice were randomly divided into three groups after a two-week acclimation period with normal standard laboratory food diet. Mice were administered PBS (PBS group as control), PBS along with DSS (DSS group, as a control), and a cocktail of paraprobiotics along with DSS (Para group). The severity of colitis, length and histopathology of the colon were evaluated. In addition, the expression of autophagy was assessed using real-time PCR. The results showed that administration of the paraprobiotic cocktail to DSS-treated mice inhibited the severity of colitis symptoms, as evidenced by the inhibition of weight loss and DAI, as well as histopathological scores in the study colon, as well as shortening of colon length caused by DSS. In contrast to the DSS group, the cocktail was able to modulate inflammation through upregulation of autophagy-related genes (becline 1, atg5, atg7, atg12, and atg13). Although there are some limitations in our investigation, such as the dosage and duration of treatments, our native paraprobiotic blend effectively prevented the advancement of colitis. This suggests that it plays a vital role in regulating inflammation and preventing colitis by promoting the autophagy mechanism in cases where the consumption of probiotics may have negative consequences.

Genistein alleviates dextran sulfate sodium-induced colitis in mice through modulation of intestinal microbiota and macrophage polarization.

Ulcerative colitis (UC) is a colonic immune system disorder, manifested with long duration and easy relapse. Genistein has been reported to possess various biological activities. However, it remains unclear whether genistein can ameliorate UC by modulating the homeostasis of the intestinal bacterial community. The dextran sodium sulfate (DSS)-induced UC mice were administrated with genistein (20mg/kg/day) or genistein (40mg/kg/day) for ten days. The general physical condition of the mice was monitored. After sacrifice, the changes in colon length and colonic pathological morphology were observed. The expression of intestinal barrier proteins, inflammatory cytokines, and macrophage markers in the colon was detected. The composition and metabolic products of the intestinal microbiota were analyzed. Genistein treatment visibly improved body weight change and disease activity index in DSS-induced mice. Genistein treatment ameliorated colonic pathological alterations and promoted the expression of mucin-2 and tight junction proteins. Genistein administration inhibited myeloperoxidase activity and colonic inflammatory cytokines. Furthermore, genistein administration improved the structure of the intestinal microbial community, promoted the production of short-chain fatty acids, and modulated macrophage polarization. These results revealed that genistein mediated macrophage polarization balance by improving intestinal microbiota and its metabolites, thereby alleviating DSS-induced colitis.

Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Effect of water content and sodium sulfate concentration on the resistivity of red clay

Effect of water content and sodium sulfate concentration on the resistivity of red clay

So Shiho Tang Reduces Inflammation in Lipopolysaccharide-Induced RAW 264.7 Macrophages and Dextran Sodium Sulfate-Induced Colitis Mice

So Shiho Tang (SSHT) is a traditional herbal medicine commonly used in Asian countries. This study evaluated the anti-inflammatory effect of SSHT and the associated mechanism using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and murine dextran sodium sulfate (DSS)-induced ulcerative colitis models. Pre-treatment of RAW 264.7 macrophages with SSHT significantly reduced LPS-induced inflammation by decreasing nitrite production and regulating the mitogen-activated protein kinase pathway. Meanwhile, in mice, DSS-induced colitis symptoms, including colon shortening and body weight loss, were attenuated by SSHT. Moreover, representative compounds of SSHT, including glycyrrhizic acid, ginsenoside Rb1, baicalin, saikosaponin A, and saikosaponin B2, were quantified, and their effects on nitrite production were measured. A potential anti-inflammatory effect was detected in LPS-induced RAW 264.7 cells. Our findings suggest that SSHT is a promising anti-inflammatory agent. Its representative components, including saikosaponin B2, ginsenoside Rb1, and baicalin, may represent the key active compounds responsible for eliciting the anti-inflammatory effects and can, therefore, serve as quality control markers in SSHT preparations.

Abstract LB349: Cysteine restriction enhances antitumor immunity in colorectal cancer

Abstract Background: Colon cancer is the second leading cause of cancer mortality worldwide, however, there are still issues with multidrug resistance and severe adverse reactions. Previous studies have shown that sulfur-containing amino acids are involved in cancer development, drug resistance, and immune evasion. Here, Our experimental findings suggested that restricting the intake of sulfur-containing amino acids may present a novel strategy for treating colorectal cancer. Methods: We assessed the impact of sulfur-containing amino acid restriction (SAR) on distinct cellular subpopulations within the tumor microenvironment through single-cell sequencing on colon carcinogenesis induced by azoxymethane/dextran sodium sulfate (AOM/DSS). Employing our custom-produced neutralizing antibodies against SLC7A11 to restrict cysteine intake, we examined the therapeutic implications and underlying molecular mechanisms by RNA-seq, Multiplexed immunofluorescence staining and Western blotting. Results: In the AOM/DSS model, SAR led to a slight reduction in mouse body weight compared to the normal diet. However, this dietary restriction significantly enhanced the survival rate of mice and effectively suppressed tumor growth. The single-cell sequencing results indicated a significant increase in the proportion of T cells within the tumor microenvironment in response to SAR. This suggested that restricting the intake of sulfur-containing amino acids may be a promising anti-tumor strategy. Previous studies have indicated high expression of the SLC7A11, a cysteine transporter protein, in various cancers, including colorectal cancer. To further investigate the role of cysteine in colorectal cancer, we developed the neutralizing antibody 1A4 against SLC7A11. Our results indicated that 1A4 markedly inhibited colorectal cancer development in mice. As known, 85% of colorectal cancers are microsatellite stable, which hardly benefit from treatment with immune checkpoint inhibitors (ICIs). Compared to anti-PD-1 and anti-CTLA4, 1A4 significantly inhibited the growth of CT26 in vivo. Multiplexed immunofluorescence staining results demonstrated that 1A4 significantly increased the proportion of CD8+ T cells in colorectal cancer tissues. Conclusion: Limiting cysteine intake significantly inhibits the growth of colorectal cancer, increases the proportion of CD8+ T cells, and enhances anti-tumor immunity. Citation Format: Jichang Li, Kang Xia, Zeruo Yang, Xiaoxue Pan, Xiaojing Yang, Pengyuan Wang, Shanwen Chen. Cysteine restriction enhances antitumor immunity in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB349.

Recombinant probiotic Lactococcus lactis delivering P62 mitigates moderate colitis in mice

Introduction and objectivep62 is a human multifunctional adaptor protein involved in key cellular processes such as tissue homeostasis, inflammation, and cancer. It acts as a negative regulator of inflammasome complexes. It may thus be considered a good candidate for therapeutic use in inflammatory bowel diseases (IBD), such as colitis. Probiotics, including recombinant probiotic strains producing or delivering therapeutic biomolecules to the host mucosal surfaces, could help prevent and mitigate chronic intestinal inflammation. The objective of the present study was to combine the intrinsic immunomodulatory properties of the probiotic Lactococcus lactis NCDO2118 with its ability to deliver health-promoting molecules to enhance its protective and preventive effects in the context of ulcerative colitis (UC).Material and methodsThis study was realized in vivo in which mice were supplemented with the recombinant strain. The intestinal barrier function was analyzed by monitoring permeability, secretory IgA total levels, mucin expression, and tight junction genes. Its integrity was evaluated by histological analyses. Regarding inflammation, colonic cytokine levels, myeloperoxidase (MPO), and expression of key genes were monitored. The intestinal microbiota composition was investigated using 16S rRNA Gene Sequencing.Results and discussionNo protective effect of L. lactis NCDO2118 pExu:p62 was observed regarding mice clinical parameters compared to the L. lactis NCDO2118 pExu: empty. However, the recombinant strain, expressing p62, increased the goblet cell counts, upregulated Muc2 gene expression in the colon, and downregulated pro-inflammatory cytokines Tnf and Ifng when compared to L. lactis NCDO2118 pExu: empty and inflamed groups. This recombinant strain also decreased colonic MPO activity. No difference in the intestinal microbiota was observed between all treatments. Altogether, our results show that recombinant L. lactis NCDO2118 delivering p62 protein protected the intestinal mucosa and mitigated inflammatory damages caused by dextran sodium sulfate (DSS). We thus suggest that p62 may constitute part of a therapeutic approach targeting inflammation.

Sedanolide alleviated DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice

IntroductionInflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear. ObjectivesIn this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice. MethodsThe mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed. ResultsSedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2. ConclusionSedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.

Anticolorectal Cancer Activity of Bilobalide in Patient-Derived Colorectal Cancer Organoids and AOM/DSS Mouse Model

Bilobalide has shown strong anti-inflammatory activity. Colorectal cancer (CRC) is closely associated with inflammation. However, no studies have reported on the use of bilobalide for treating CRC. This study aims to evaluate the effect of bilobalide on CRC prevention. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunofluorescence showed that bilobalide significantly inhibits the M2 polarization of macrophages dependent on phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4). Analysis of signaling pathways showed that the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) was regulated. In particular, human CRC organoids were established. Western blotting, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and analysis of cell viability and morphology further supported the hypothesis that the anti-CRC effects of bilobalide could be explained by its ability to suppress M2 macrophage polarization and promote M1 transformation. C57BL/6 mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) were divided into three groups, i.e., control, AOM/DSS, low (2.5 mg/kg), and high (5 mg/kg). High-dose bilobalide markedly inhibited the progression of CRC, as evidenced by the increased body weight, decrease in disease activity index (DAI) death rate, and alleviation of colon length reduction and tumorigenesis. According to the in vivo results, reduced levels of inflammatory cytokines in the serum included tumor necrosis factor (TNF-α), IL-6, IL-1β, and IL-10. Bilobalide reduced oxidative stress indices, lipid peroxide (LPO), and malondialdehyde (MDA) and increased reduced glutathione (GSH). In addition, the expression of proliferating cell nuclear antigen (PCNA), Ki67, cellular Myc (c-Myc), and CD206 was downregulated in the drug-treated groups, as confirmed by the immunohistochemical staining. Collectively, these results indicated that bilobalide administration improve experimental CRC by inhibiting M2 macrophage polarization and oxidative stress. Thus, bilobalide may prevent CRC and serve as a potential therapeutic target for CRC.