Pectic oligosaccharides ameliorate high-fat diet-induced obesity and hepatic steatosis in association with modulating gut microbiota in mice.

Accumulating evidence has shown that gut microbiota and its metabolites have important significance in the etiology of obesity and related disorders. Prebiotics prevent and alleviate obesity by modulating the gut microbiota. However, how pectin oligosaccharides (POS) derived from pectin degradation affect gut microbiota and obesity remains unclear. To investigate the potential anti-obesity effects of POS, mice were fed a high-fat diet (HFD) for 12 weeks and a POS supplement with drinking water during the last 8 weeks. The outcomes demonstrated that POS supplementation in HFD-fed mice decreased body weight (P < 0.01), improved glucose tolerance (P < 0.001), reduced fat accumulation (P < 0.0001) and hepatic steatosis, protected intestinal barrier, and reduced pro-inflammatory cytokine levels. After fecal metagenomic sequencing, the POS corrected the gut microbiota dysbiosis caused by the HFD, as shown by the increased populations of Bifidobacterium, Lactobacillus taiwanensis, and Bifidobacterium animalis, and decreased populations of Alistipes and Erysipelatoclostridium, which were previously considered harmful bacteria. Notably, the changed gut microbiota was associated with the obesity prevention of POS. These findings demonstrate that POS regulates particular gut microbiota, which is essential owing to its ability to prevent disorders associated with obesity.

Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4+ T cell apoptosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe white matter demyelination. Because of its complex pathogenesis, there is no definite cure for MS. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties with several autoimmune diseases. It is also used to inhibit acute immune rejection due to its anti-inflammatory and immunosuppressive properties. However, it is unclear whether ATO has a therapeutic effect on EAE, and the underlying mechanisms have not yet been clearly elucidated. In this study, we attempted to assess whether ATO could be used to ameliorate EAE in mice. METHODS: ATO (0.5 mg/kg/day) was administered intraperitoneally to EAE mice 10 days post-immunization for 8 days. On day 22 post-immunization, the spinal cord, spleen, and blood were collected to analyze demyelination, inflammation, microglia activation, and the proportion of CD4+ T cells. In vitro, for mechanistic studies, CD4+ T cells were sorted from the spleen of naïve C57BL/6 mice and treated with ATO and then used for an apoptosis assay, JC-1 staining, imaging under a transmission electron microscope, and western blotting. RESULTS: ATO delayed the onset of EAE and alleviated the severity of EAE in mice. Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation, and decreased the expression levels of IL-2, IFN-γ, IL-1ß, IL-6, and TNF-α in EAE mice. Moreover, the number and proportion of CD4+ T cells in the spinal cord, spleen, and peripheral blood were reduced in ATO-treated EAE mice. Finally, ATO induced CD4+ T cell apoptosis via the mitochondrial pathway both in vitro and in vivo. Additionally, the administration of ATO had no adverse effect on the heart, liver, or kidney function, nor did it induce apoptosis in the spinal cord. CONCLUSIONS: Overall, our findings indicated that ATO plays a protective role in the initiation and progression of EAE and has the potential to be a novel drug in the treatment of MS.

Combination of N, N'-dicyclohexyl-N-arachidonic acylurea and tacrolimus prolongs cardiac allograft survival in mice.

Current immunosuppressive agents for organ transplantation are not ideal because of their strong toxicity and adverse effects. Hence, there is an urgent need to develop novel immunosuppressive agents. The compound N, N'-dicyclohexyl-N-arachidonic acylurea (DCAAA) is a novel highly unsaturated fatty acid from the traditional Chinese medicinal plant Radix Isatidis. In this study, we systematically investigated the toxicity, immunosuppressive effect and mechanisms underlying the activity of DCAAA. The toxicity tests showed that DCAAA treatment did not lead to red blood cell hemolysis and did not affect the liver and kidney functions in mice. The lymphocyte transformation test showed that DCAAA treatment inhibited lymphocyte proliferation in a dose-dependent manner. An in vivo cardiac allotransplantation experiment showed that DCAAA treatment could suppress the immune rejection and significantly prolong the survival of cardiac allografts in recipient mice by reducing the proportion of CD4+ T cells in the spleen and grafts, concentration of interferon-γ in the supernatant and serum and infiltration of inflammatory cells into the grafts. Moreover, a combination treatment with DCAAA and tacrolimus had a synergistic effect in preventing acute rejection of heart transplants. In vitro molecular biology experiments showed that DCAAA treatment inhibited activation of the T-cell receptor-mediated phosphoinostide 3-kinase-protein kinase B pathway, thereby arresting cell cycle transition from the G1 to the S phase, and inhibiting lymphocyte proliferation. Overall, our study reveals a novel, low-toxicity immunosuppressive agent that has the potential to reduce the toxic side effects of existing immunosuppressive agents when used in combination with them.

[Effect of Different Adding Means of Ignited Water Purification Sludge on Phosphorus Adsorption and Forms].

The adsorption of external phosphorus (P) and the distribution of dissolved inorganic P (DIP) in the sediment interstitial water and sedimentary P forms were researched under the ignited water purification sludge (IWPS) addition (mixing and capping). The results showed that the adsorption ability of the IWPS increased obviously, compared with the water purification sludge (WPS). It indicated that the Smax increased by 43.7%, the EPC0 decreased by 69.1% and the DPS decreased by 54.4%. The contribution of P disappearance in the overlying water had almost no difference between the mixing and capping with IWPS, but it was obviously higher than the control in both cases. Under the mixing condition, the adsorption of external P by unit IWPS was 2.3 times of that under the capping condition, if the contacting probability between the IWPS and the overlying water was considered. Under the capping condition, the DIP in the sediment interstitial water (1-2 cm) was 33.17 times (average) of that under the mixing condition. It was attributed to the decrease of the dissolved oxygen penetration due to capping. Under the mixing condition, the external P tended to form Ca-P, while the percentages of NH4Cl-P and Fe/Al-P to Tot-P were bigger under the capping condition. It was suggested that the improvement of the sedimentary microenvironment by mixing with the IWPS was favorable for the adsorption of the external P and the immobilization of the internal P.

[External Phosphorus Adsorption and Immobility with the Addition of Ignited Water Purification Sludge].

The cumulative adsorption of external phosphorus (P) by water purification sludge after ignition under different addition methods (mix and cover) was investigated along with the adsorption isotherm and the release of internal P after external P adsorption. The cumulative adsorption of external P was 11.496 mg (mix) and 11.042 mg (cover) and these values were higher than those in the control (7.219 mg). The maximum sorption capacity (Smax) increased under the mix and cover and the former (7.795 mg·g-1) was higher than the latter (6.807 mg·g-1). However, the zero equilibrium P concentration (EPC0) in the mix was 0.83 mg·L-1, higher that in the cover (0.64 mg·L-1). The result suggests that the internal P was easily released in the mix method, compared to the cover method. Under anaerobic conditions, the release of the internal P was 0.93 mg in the mix, lower than that in the cover (1.49 mg) and in the control (7.76 mg). In addition, the specific release rate in the cover method was 0.00614 (mean), higher than that (0.00396) in the mix method. Noticeably, these data were lower than those in the control, indicating that the retention of P under the mix method was higher, compared to the cover and the control and it is challenging to evaluate the P retention with EPC0.

[Impacts of Multiple Disturbance on Migration and Transformation of Endogenous Phosphorus in Lake].

This work aimed to clarify the influence of multiple disturbance factors on the migration and transformation of endogenous phosphorus. In this experiment, the sediment of Meiliang Bay in Taihu Lake was studied as the major research object. With the help of Rhizon sampling technique, Unisense microelectrode system and so on, this experiment studied the change regularities of dissolved oxygen between sediment and water interface, different forms of phosphorus and iron ions under disturbance. The results indicated that the dissolved oxygen content in sediment decreased in the presence of Corbicula fluminea as compared with the control experiment. Disturbance made the peak area of DIP in interstitial water to migrate from 3-4 cm to 4-5 cm, which suggested that the "active region" of DIP regeneration went deeply into sediment with the appearance of Chironomus plumosus and Corbicula fluminea. Meanwhile, the existence of Corbicula fluminea and algae further reduced DIP in the interstitial water. That was because the released NH4Cl-P was transferred to phosphorus in overlying water and Fe/Al-P. With the increase of disturbance factors, the transformation ratio from NH4Cl-P to Fe/Al-P also increased gradually (from 44% to 59%).