Sodium sulphate ameliorates hypercholesterolemia via the upregulation of Cyp7a1 in hepatocytes and alleviates hepatic insulin resistance via the downregulation of Trib3 in mice with high cholesterol diets.

Amelioration of hypercholesterolemia is essential for the treatment of atherosclerotic cardiovascular disease. Sodium sulphate is the effective component of mirabilite, which has been used in traditional Chinese medicine for the treatment of various diseases. In the present study, C57BL/6 mice were fed with a high-cholesterol diet (HCD) for 7 weeks and were treated with sodium sulphate in the last three of those weeks. Sodium sulphate significantly reduced the total cholesterol level and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in the serum of mice fed the HCD. In addition, cytochrome P450 7a1 and 39a1 were significantly upregulated in the livers of mice treated with sodium sulphate. Furthermore, tribbles pseudokinase 3 expression was significantly increased in the livers of mice fed the HCD, but was significantly reduced by sodium sulphate treatment. In terms of the insulin signaling pathway, the ratio of phosphorylated AKT to total AKT in the livers of mice fed the HCD was significantly lower compared with that of control mice fed a normal diet, but was significantly increased by sodium sulphate treatment. Sodium sulphate treatment also reduced the levels of fibroblast growth factor (FGF)15 in the ileum and inhibited the FGF15/FGF receptor 4-Klotho ß/c-Jun N-terminal kinase/c-Jun signaling pathway in the livers of mice fed the HCD. In addition, sodium sulphate changed the composition of the gut microbiota of mice fed the HCD. In conclusion, sodium sulphate may mitigate hypercholesterolemia and hepatic insulin resistance in mice fed an HCD.

Dietary sodium sulphate supplementation during mid-to-late gestation improves placental angiogenesis, bile acid metabolism, and serum amino acid concentrations of sows.

Sulphate plays a vital role in the growth and development of the foetus. Sodium sulphate (Na2SO4) is utilised as a dietary protein nutrient factor and helps replenish sulphur elements in livestock and poultry. Therefore, this study aimed to investigate the effects of Na2SO4 supplementation in mid to late pregnancy on bile acid metabolism, amino acid metabolism, placental vascular development and antioxidant capacity of sows. At day 1 of gestation (G1), a total of twenty-six primiparous sows were carefully chosen and randomised into two groups: (1) control group, (2) Na2SO4 group (1.40 g/kg). Blood samples and placentas from sows were collected to measure biochemistry parameters, antioxidant indexes, placental vascular density, and indicators related to bile acid metabolism and amino acid concentrations, respectively. We found that dietary supplementation with Na2SO4 had a tendency for a reduction of incidence of stillborn at farrowing. Further observation showed that sows supplemented with Na2SO4 had decreased total bile acid level in cord blood, and increased placental gene expression of sulphotransferase and organic anion transport peptide. Na2SO4 supplementation increased catalase and total superoxide dismutase activity in cord blood, decreased placental malondialdehyde content, and enhanced placental protein expression of Sirtuin 1. Moreover, Na2SO4 consumption resulted in increased vascular density of placental stroma and elevated amino acid levels in sows and cord blood. Furthermore, maternal Na2SO4 consumption reduced serum urea concentrations of sows and umbilical cord blood at G114. In addition, dietary supplementation with Na2SO4 activated the protein expression of the placental mechanistic target of rapamycin complex 1. Collectively, these findings indicated that maternal supplementation with Na2SO4 during mid-to-late gestation elevated foetal survival via improving placental angiogenesis, bile acid metabolism and amino acid utilisation.

Huangqin tang alleviates colitis-associated colorectal cancer via amino acids homeostasisand PI3K/AKT/mtor pathway modulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. AIMS OF THE STUDY: The purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. METHODS: We established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. RESULTS: The data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. CONCLUSION: HQT is effective in alleviating and delaying the colon "inflammation-to-cancer". The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC.

Solute Transporter OCTN1/Slc22a4 Affects Disease Severity and Response to Infliximab in Experimental Colitis: Role of Gut Microbiota and Immune Modulation.

BACKGROUND: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis. METHODS: A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively. RESULTS: Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells. CONCLUSIONS: Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies.

In this article, we evaluated the role of OCTN1, an organic cation transporter, in modifying gut microbiota and immune T cell populations, as well as its effects on experimental colitis and the response to infliximab treatment.

Influence of Carboxymethyl Cellulose as a Thickening Agent for Glauber's Salt-Based Low Temperature PCM.

This work is focused on a novel, promising low temperature phase change material (PCM), based on the eutectic Glauber's salt composition. To allow phase transition within the refrigeration range of temperatures of +5 °C to +12 °C, combined with a high repeatability of melting-freezing processes, and minimized subcooling, the application of three variants of sodium carboxymethyl cellulose (Na-CMC) with distinct molecular weights (700,000, 250,000, and 90,000) is considered. The primary objective is to optimize the stabilization of this eutectic PCM formulation, while maintaining the desired enthalpy level. Preparation methods are refined to ensure repeatability in mixing components, thereby optimizing performance and stability. Additionally, the influence of Na-CMC molecular weight on stabilization is examined through differential scanning calorimetry (DSC), T-history, and rheology tests. The PCM formulation of interest builds upon prior research in which borax, ammonium chloride, and potassium chloride were used as additives to sodium sulfate decahydrate (Glauber's salt), prioritizing environmentally responsible materials. The results reveal that CMC with molecular weights of 250 kg/mol and 90 kg/mol effectively stabilize the PCM without phase separation issues, slowing crystallization kinetics. Conversely, CMC of 700 kg/mol proved ineffective due to the disruption of gel formation at its low gel point, hindering higher concentrations. Calculations of ionic concentration indicate higher Na ion content in PCM stabilized with 90 kg/mol CMC, suggesting increased ionic interactions and gel strength. A tradeoff is discovered between the faster crystallization in lower molecular weight CMC and the higher concentration required, which increases the amount of inert material that does not participate in the phase transition. After thermal cycling, the best formulation had a latent heat of 130 J/g with no supercooling, demonstrating excellent performance. This work advances PCM's reliability as a thermal energy storage solution for diverse applications and highlights the complex relationship between Na-CMC molecular weight and PCM stabilization.

The immunomodulatory effects of probiotics and azithromycin in dextran sodium sulfate-induced ulcerative colitis in rats via TLR4-NF-κB and p38-MAPK pathway.

Ulcerative colitis (UC), a chronic autoimmune disease of the gut with a relapsing and remitting nature, considers a major health-care problem. DSS is a well-studied pharmacologically-induced model for UC. Toll-Like Receptor 4 (TLR4) and its close association with p-38-Mitogen-Activated Protein Kinase (p-38 MAPK) and nuclear factor kappa B (NF-κB) has important regulatory roles in inflammation and developing UC. Probiotics are gaining popularity for their potential in UC therapy. The immunomodulatory and anti-inflammatory role of azithromycin in UC remains a knowledge need. In the present rats-established UC, the therapeutic roles of oral probiotics (60 billion probiotic bacteria per kg per day) and azithromycin (40 mg per kg per day) regimens were evaluated by measuring changes in disease activity index, macroscopic damage index, oxidative stress markers, TLR4, p-38 MAPK, NF-κB signaling pathway in addition to their molecular downstream; tumor necrosis factor alpha (TNFα), interleukin (IL)1ß, IL6, IL10 and inducible nitric oxide synthase (iNOS). After individual and combination therapy with probiotics and azithromycin regimens, the histological architecture of the UC improved with restoration of intestinal tissue normal architecture. These findings were consistent with the histopathological score of colon tissues. Each separate regimen lowered the remarkable TLR4, p-38 MAPK, iNOS, NF-κB as well as TNFα, IL1ß, IL6 and MDA expressions and elevated the low IL10, glutathione and superoxide dismutase expressions in UC tissues. The combination regimen possesses the most synergistic beneficial effects in UC that, following thorough research, should be incorporated into the therapeutic approach in UC to boost the patients' quality of life.

Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-ß, Hp-TGM.

In animal models of inflammatory colitis, pathology can be ameliorated by several intestinal helminth parasites, including the mouse nematode Heligmosomoides polygyrus. To identify parasite products that may exert anti-inflammatory effects in vivo, we tested H. polygyrus excretory-secretory (HES) products, as well as a recombinantly expressed parasite protein, transforming growth factor mimic (TGM), that functionally mimics the mammalian immunomodulatory cytokine TGF-ß. HES and TGM showed a degree of protection in dextran sodium sulphate-induced colitis, with a reduction in inflammatory cytokines, but did not fully block the development of pathology. HES also showed little benefit in a similar acute trinitrobenzene sulphonic acid-induced model. However, in a T cell transfer-mediated model with recombination activation gene (RAG)-deficient mice, HES-reduced disease scores if administered throughout the first 2 or 4 weeks following transfer but was less effective if treatment was delayed until 14 days after T cell transfer. Recombinant TGM similarly dampened colitis in RAG-deficient recipients of effector T cells, and was effective even if introduced only once symptoms had begun to be manifest. These results are a promising indication that TGM may replicate, and even surpass, the modulatory properties of native parasite HES.

Boswellic acid coated zinc nanoparticles attenuate NF-κB-mediated inflammation in DSS-induced ulcerative colitis in rats.

INTRODUCTION: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, and until now therapeutic agents for UC still cannot exert satisfied effects. Therefore, this study aimed to investigate the ameliorative effect of boswellic acid coated zinc nanoparticles (BAs-ZnNPs) on dextran sodium sulphate (DSS) induced-UC in rats. METHODS: Rats were divided into five groups; control, BAs-ZnNPs, DSS, DSS+BAs, and DSS + BAs-ZnNPs. The activity of alkaline phosphatase (ALP) was determined colorimetrically, while the concentration of IgM, IgG, TNF-α, IL-1ß, and IL-8 were measured by ELISA. Levels of gene expression of NF-κB and COX-2 genes were evaluated by RT-qPCR, while the expression of protein levels of PI3K and STAT-3 were done by western blotting. Finally, histopathological examination of colon tissues of different groups of rats was done. RESULTS: The depicted ball-like structure of the BAs-ZnNPs in the TEM images ranging in size from 50 to 100 nm in diameter while their formation was confirmed by UV-visible spectroscopy with a sharp peak of maximum absorbance at 266 nm. Our results revealed that BAs-ZnNPs exerted an anti-inflammatory effect in the experimental model of colitis, demonstrated histologically and biochemically as shown by the improvement of ALP, IgM, IgG, and the gene expression levels of NF-κB and COX-2. Also, this beneficial effect was associated with the reduction in the expression of TNF-α, IL-1ß, IL-8, PI3K, and STAT-3. Thus, this effect improves the altered immune response associated with the colonic inflammation. CONCLUSION: BAs-ZnNPs can be proposed as a therapeutic candidate to attenuate UC. The potential underlying mechanism includes suppression of ALP, IgM, IgG, IL-1ß, and IL-8 levels via regulation of NF-κB and COX-2 gene expression and STAT-3 and PI3K protein expression in a UC rat model.

Dietary Strategies to Modulate the Health Condition and Immune Responses in Gilthead Seabream (Sparus aurata) Juveniles Following Intestinal Inflammation.

Several feed additives have proved to be beneficial in eliciting fish health. Β-glucans and curcumin are compounds with immunomodulatory capacities known to increase growth performance, stimulate immunity, improve general health, and enhance disease resistance in fish. The present study aimed to evaluate the effects of dietary Phaeodactylum tricornutum extracts rich in ß-glucans and curcumin on gilthead seabream health status prior to and following an intestinal inflammatory stimulus. Three experimental diets were formulated: a practical commercial-type diet (CTRL), a CTRL diet supplemented with 1% microalgae-derived ß-glucans extract (BG), and a CTRL diet supplemented with 0.2% of curcumin (CUR). After 30 days of the feeding trial, fish were sampled and subjected to an oral administration of 1% dextran sodium sulphate (DSS) to induce intestinal inflammation. Four groups were considered: a group of fish continued to be fed on the CTRL diet while the remaining groups were exposed to DSS, including CTRL-D (CTRL + DSS), BG-D (BG + DSS), and CUR-D (CUR + DSS), for 6 days. Growth, plasma and gut humoral immunity, liver and gut oxidative stress biomarkers, and intestinal gene expression were evaluated. No significant differences were found in growth after 30 days of feeding; however, seabream fed BG had decreased anti-protease activity and nitric oxide concentration in plasma while those fed CUR had increased mRNA levels of the tnfα, csf1r, and hep genes compared to those fed CTRL. After the inflammatory stimulus, hematocrit was enhanced in fish fed BG-D and CUR-D while red blood cell counts increased in those fed CTRL-D. Superoxide dismutase activity decreased in the intestine of all DSS groups while lipid peroxidation increased in the gut of fish fed CTRL-D and BG-D compared to CTRL. Moreover, the mRNA expression levels of csfr1 and sod decreased in fish fed CTRL-D and BG-D compared to CTRL, respectively. Despite the mild intestinal inflammatory condition induced by DSS, CUR was able to partially ameliorate its effects, improving the hematological profile and assisting against the oxidative stress.

Treatment of inflammatory bowel disease: Potential effect of NMN on intestinal barrier and gut microbiota.

Nicotinamide mononucleotide (NMN) exerts physiological effects in mammals through its conversion to nicotinamide adenine dinucleotide (NAD+). In this study, we established experimental models of colitis by mixing drinking water of C57BL/6J mice with dextran sodium sulphate (DSS), and then fed them with the same concentration of NMN or at the same time. After NMN treatment, we observed improved morphology of inflamed intestines, slightly restored length of colon, improved barrier function and reduced proinflammatory factors expression in serum. Also, significant alterations in the composition and abundance of intestinal flora in IBD mice were found. The abundance of Firmicutes, Verrucomicrobia, Akkermansia and Lactobacillus, considered as beneficial bacteria, increased, while Bacteroidetes and Muribaculaceae unclassifiably decreased. Taken together, these results suggest that NMN may improve intestinal inflammation, reduce intestinal mucosal permeability and repair gut flora dysbiosis in IBD.

Assessment of Hot Corrosion in Molten Na2SO4 and V2O5 of Inconel 625 Fabricated by Selective Laser Melting versus Conventional Technology.

Inconel 625 samples, obtained by Selective Laser Melting (SLM) and conventional technology, were tested for hot corrosion resistance against a molten mixture of Na2SO4 and V2O5. The assessments were performed in air, at 900 °C with exposure time of up to 96 h, and at 1000 °C for 8 h. Weight gain was higher for samples obtained by SLM, with 37.4% after 8 h, 3.98% after 24 h, 4.46% after 48 h, and 5.8% after 96 h at 900 °C (22.6% at 1000 °C, 8 h). Three stages of corrosion were observed, the first and last with a high corrosion rate, while the second one showed a slower corrosion rate. Corrosion behaviour depends on the morphology of the grain boundary, which can influence the infiltration of corrosive salts, and on the formation of Cr2NiO4 compound, which acts as a temporary barrier.

Melatonin mediated inhibition of EZH2-NOS2 crosstalk attenuates inflammatory bowel disease in preclinical in vitro and in vivo models.

AIMS: Inflammatory Bowel Disease is characterised by abdominal pain, diarrhoea, rectal bleeding and weight loss. Sometimes it may leads to severe health complications resulting in death of an individual. Current research efforts to highlight the role of melatonin in regulating EZH2, a master epigenetic regulator and its beneficiary effect in case of IBD management. MATERIAL METHODS: Murine macrophages (RAW 264.7) were treated with lipopolysaccharides (LPS) to activate them for generating inflammatory response to investigate efficacy of melatonin in-vitro models. Similarly, for developing in vivo models, Dextran sodium sulphate (36-50 kDa) was used. Evaluations of anti-inflammatory activities were carried out by nitrite assay, western blotting, q-PCR, immunofluorescence, and histological studies. KEY FINDINGS: Reduction of epigenetic target, EZH2 by melatonin significantly improves the clinical symptoms of dextran sodium sulphate induced colitis and may be implicated as a potential therapeutic target in IBD management. The present study evaluates the efficacy of melatonin by epigenetic regulation in IBD models. Down regulation of EZH2 by melatonin reduced the chemical induced inflammatory insults in in vitro and in vivo models. Exploration of molecular pathways has revealed interlink of EZH2 and NOS2, a hallmark of inflammation. Molecular mechanistic action of melatonin is attributed to inhibition of the expression and physical interaction of EZH2 and NOS2. SIGNIFICANCE: Our study highlights melatonin therapeutic effect via attenuating interaction between EZH2 and NOS2 which is beneficial in managing IBD treatment.

Oral administration of Lactobacillus paracasei N1115 on neonatal mice prevents the intestinal inflammation in adulthood.

Colonization and development of gut microbiota during early life stage plays a key regulatory role in the establishment of the host-microbial relationship, which was conducive to progressing host immunity and maintaining health throughout the adulthood life span. This study was aimed to evaluate the protective effect from inflammatory bowel disease (IBD) in adulthood based on the early intervention of Lactobacillus paracasei N1115 (LP N1115). LP N1115 treatment was carried out during 2 weeks in postnatal mice. Then the dextran sodium sulphate (DSS)-induced colitis model mice were established in adulthood, and the status of intestinal tissues was detected. Results showed the decreased severity of intestinal tissue injury, cell apoptosis, and proinflammatory cytokines expression in DSS-induced model with LP N1115 early intervention. Therefore, the intake of LP N1115 in neonatal mice has played a long-term healthy role in the prevention of intestinal injury and inflammation in adulthood.

Improvements in the methodology for fatty acids analysis in meat products: One-stage transmethylation and fast-GC method.

The quantification of fatty acids (FA) in meat products is frequently carried out by two-stage methylation procedures followed by long gas chromatography (GC) runs. This work aimed to simplify this methodology by means of a one-stage transmethylation method and a fast GC run, evaluating the influence of sample preparation, reagents and type of heating on the amount of FA in different meat products and optimizing a fast GC-FID (flame ionization detector) run. This allowed to establish the optimum combination of parameters (methanol + chlorotrimethylsilane, lyophilized samples and oven heating) to achieve the quantification of the highest possible amount of FA and to reduce the time of GC run from 60 to 10 min. The quality evaluation of this method obtained satisfactory results. Thus, the quantification of FA in meat products was achieved in a straightforwardly and quickly way by using a one-stage transmethylation procedure followed by a fast GC-FID run.

Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses.

Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles (EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury, and vice versa. This review discusses the roles of such EVs in regulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions, and the potential applications, advantage and concerns for using EV-based therapeutic approaches to treat such conditions, including their potential role of drug carriers for the treatment of infectious diseases.

The Effect of Lactobacillus casei on Experimental Porcine Inflammatory Bowel Disease Induced by Dextran Sodium Sulphate.

BACKGROUND: Gastrointestinal injury caused by dextran sodium sulphate (DSS) is a reliable porcine experimental model of inflammatory bowel disease (IBD). The purpose of this study was to evaluate the effect of probiotic Lactobacillus casei DN 114001 (LC) on DSS-induced experimental IBD. RESULTS: Eighteen female pigs (Sus scrofa f. domestica, weight 33-36 kg, age 4-5 months) were divided into 3 groups (6 animals per group): controls with no treatment, DSS, and DSS + LC. LC was administered to overnight fasting animals in a dietary bolus in the morning on days 1-7 (4.5 × 1010 live bacteria/day). DSS was applied simultaneously on days 3-7 (0.25 g/kg/day). On day 8, the pigs were sacrificed. Histopathological score and length of crypts/glands (stomach, jejunum, ileum, transverse colon), length and width of villi (jejunum, ileum), and mitotic and apoptotic indices (jejunum, ileum, transverse colon) were assessed. DSS increased the length of glands in the stomach, length of crypts and villi in the jejunum and ileum, and the histopathological score of gastrointestinal damage, length of crypts and mitotic activity in the transverse colon. Other changes did not achieve any statistical significance. Administration of LC reduced the length of villi in the jejunum and ileum to control levels and decreased the length of crypts in the jejunum. CONCLUSIONS: Treatment with a probiotic strain of LC significantly accelerated regeneration of the small intestine in a DSS-induced experimental porcine model of IBD.

Nose-to-brain delivery: A comparative study between carboxymethyl chitosan based conjugates of dopamine.

Herein, the synthesis of a novel polymeric conjugate N,O-CMCS-Dopamine (DA) based on an amide linkage is reported. The performances of this conjugate were compared with those of an analogous N,O-CMCS-DA ester conjugate previously studied (Cassano et al., 2020) to gain insight into their potential utility for Parkinson's disease treatment. The new amide conjugate was synthesized by standard carbodiimide coupling procedure and characterized by FT-IR, 1H NMR spectroscopies and thermal analysis (Differential Scanning Calorimetry). In vitro mucoadhesive studies in simulated nasal fluid (SNF) evidenced high adhesive effect of both ester and amide conjugates. Results demonstrated that the amide conjugate exerted an important role to prevent DA spontaneous autoxidation both under stressed conditions and physiological mimicking ones. MTT test indicated cytocompatibility of the amide conjugate with Olfactory Ensheating Cells (OECs), which were shown by cytofluorimetry to internalize efficiently the conjugate. Overall, among the two conjugates herein studied, the N,O-CMCS-DA amide conjugate seems a promising candidate for improving the delivery of DA by nose-to-brain administration.

Intestinal anti-inflammatory activity of the total alkaloid fraction from Fumaria capreolata in the DSS model of colitis in mice.

Fumaria genus has been traditionally used for managing inflammatory and gastrointestinal disorders. The study evaluates the immunomodulatory potential of the total alkaloid fraction from Fumaria capreolata L. (AFC) in primary macrophages and the intestinal anti-inflammatory effect in a dextran sodium sulphate-induced colitis in mice. AFC inhibited LPS-stimulated bone marrow-derived macrophages gene expression program dose-dependently. In vivo, AFC markedly reduced macroscopic and microscopic signs of intestinal inflammation. Besides, it restored the colonic expression of pro-inflammatory and anti-inflammatory mediators, as well as enhanced the expression of intestinal barrier markers. These results demonstrate the potential of AFC extract as a therapeutic tool for the management of inflammatory bowel disease.

The Effects of the Marine-Derived Polysaccharides Laminarin and Chitosan on Aspects of Colonic Health in Pigs Challenged with Dextran Sodium Sulphate.

This study examined the effects of dietary supplementation with laminarin or chitosan on colonic health in pigs challenged with dextran sodium sulphate (DSS). Weaned pigs were assigned to: (1) a basal diet (n = 22); (2) a basal diet + laminarin (n = 10); and (3) a basal diet + chitosan (n = 10). On d35, the basal group was split, creating four groups: (1) the basal diet (control); (2) the basal diet + DSS; (3) the basal diet + laminarin + DSS; and (4) the basal diet + chitosan + DSS. From d39-42, the pigs were orally challenged with DSS. On d44, colonic tissue/digesta samples were collected. The basal DSS group had reduced growth, higher pathology score and an increased expression of MMP1, IL13 and IL23 compared with the controls (p < 0.05); these parameters were similar between the DSS-challenged groups (p > 0.05). In the basal DSS group, the relative abundance of beneficial taxa including Prevotella and Roseburia were reduced while Escherichia/Shigella were increased, compared with the controls (p < 0.05). The relative abundance of Escherichia/Shigella was reduced and the molar proportions of acetate were increased in the laminarin DSS group compared with the basal DSS group (p < 0.01), suggesting that laminarin has potential to prevent pathogen proliferation and enhance the volatile fatty acid profile in the colon in a porcine model of colitis.

TGF-ß/Smad and JAK/STAT pathways are involved in the anti-fibrotic effects of propylene glycol alginate sodium sulphate on hepatic fibrosis.

Liver fibrosis, a consequence of unhealthy modern lifestyles, has a growing impact on human health, particularly in developed countries. Here, we have explored the anti-fibrotic effects of propylene glycol alginate sodium sulphate (PSS), a natural extract from brown algae, in fibrotic mice and cell models. Thus, we established bile duct ligature and carbon tetrachloride mouse models and LX-2 cell models with or without PSS treatment. Liver pathological sections and the relevant indicators in serum and liver tissues were examined. PSS prevented hepatic injury and fibrosis to a significant extent, and induced up-regulation of matrix metalloproteinase-2 and down-regulation of tissue inhibitor of metalloproteinase-1 through suppressing the transforming growth factor ß1 (TGF-ß1)/Smad pathway. PSS additionally exerted an anti-autophagy effect through suppressing the Janus kinase (JAK) 2/transducer and activator of transcription 3 (STAT3) pathway. In conclusion, PSS prevents hepatic fibrosis by suppressing inflammation, promoting extracellular matrix (ECM) decomposition and inactivating hepatic stellate cells through mechanisms involving the TGF-ß1/Smad2/3 and JAK2/STAT3 pathways in vivo and in vitro.