Few data are available about the effects of complexation of polyphenols with polysaccharide on their bioavailability. The complex of tea polyphenols (TP) with oat β-glucan was characterized by ultraviolet-visible spectrometry, Fourier transform infrared spectrometry, differential scanning calorimetry, atomic force microscopy, and solid-state (13)C NMR spectroscopy. The results indicated that the bonds which governed the interaction between TP and oat β-glucan were strong hydrogen bonds. The in vitro antioxidant activity of TP, β-glucan, their complex, and physical mixture was assessed using four systems, namely, DPPH(•), OH(•), and O(2)(•-) scavenging activities and reducing power. The complexation and blending of TP and β-glucan exhibited different impacts on the index of in vitro and in vivo antioxidant capacities. In the concentration range of 0.5-2.5 mg mL(-1), the complex had highest O(2)(•-) scavenging activity, whereas the highest OH(•) scavenging activity was found with the physical mixture. For antioxidant testing in vivo, there was no significant difference between the complex and the physical mixture in terms of glutathione peroxidase activity and levels of malondialdehyde and total antioxidant capacity in serums. However, the complex exhibited much higher activities of superoxide dismutase and glutathione peroxidase in livers than the physical mixture. The present study provided a deeper understanding of the influence of molecular interaction between TP and oat β-glucan on their antioxidant activities.

Genes could be used to treat atherosclerosis. The key problem is how to target a gene through the walls of arteries in free-flowing blood. TFPI-2 has been shown to suppress thrombosis and arterial re-stenosis, which indicates its potential function in gene therapy for atherosclerosis. The microbubble ultrasound contrast agent is widely applied in diagnostic imaging, and could be used for transferring genes into arteries. By transfecting TFPI-2 into arteries using SonoVue (a kind of microbubble ultrasound contrast agent), we identified TFPI-2 as an available factor for inhibiting the proliferation of vascular endothelial cells in vivo. Compared with adenovirus, SonoVue showed similar gene transfection efficiency, but the latter showed stronger inhibition of thrombosis and arterial re-stenosis with a high expression of TFPI-2 protein in vitro and in vivo. SonoVue was less damaging when transfecting genes into the arterial wall. These data indicate that transfecting human TFPI-2 into the arterial wall may suppress thrombosis and arterial re-stenosis, and reduce atherosclerosis.

Schwann cells are the main supportive cells of the peripheral nerves. Schwann cells suffer inhibition of autophagy under hyperglycemia treatment in diabetic peripheral neuropathy (DPN). However, the exact mechanism is still not fully elucidated. We first observed the decrease of autophagy markers (LC3‐II/LC3‐I, P62) in the sciatic nerves of diabetic mice vs. normal mice, accompanied with the loss of myelinated nerve fibers and abnormal myelin sheath. In line with this, LC3‐II/LC3‐I and P62 were also significantly reduced in high glucose—treated rat Schwann cell 96 (RSC96) cells compared with normal glucose—treated cells. Furthermore, we found that trichostatin A [an inhibitor of histone deacetylase (HDAC)] evidently improved LC3‐II/LC3‐I in high glucose—treated RSC96 cells, without an effect on P62 expression. Again, HDAC1 and HDAC5 were revealed to be increased in RSC96 cells stimulated with high glucose. Inhibition of HDAC1 but not HDAC5 by small hairpin RNA vector enhanced LC3‐II/LC3‐I in high glucose—cultured RSC96 cells. In addition, LC3‐II conversion regulators [autophagy‐related protein (Atg)3, Atg5, and Atg7] were detected in high glucose—treated and HDAC1‐knockdown RSC96 cells, and Atg3 was proven to be the key target of HDAC1. The presuppression of Atg3 offset the improvement of LC3‐II/LC3‐I resulting from HDAC1 inhibition in high glucose—treated RSC96 cells. The Janus kinase (JAK)—signal transducer and activator of transcription (STAT) signaling pathway was activated in RSC96 cells treated with high glucose, which was indicated by increased STAT3 phosphorylation. Blocking STAT3 phosphorylation by chemical inhibitor AG490 induced HDAC1 down‐regulation followed by increases in Atg3 and LC3‐II/LC3‐I. Interestingly, we also found that AG490 treatment enhanced P62 expression in high glucose—stimulated RSC96 cells. Taken together, our findings demonstrate that hyperglycemia inhibits LC3‐II/LC3‐I in an HDAC1‐Atg3—dependent manner and decreases P62 expression in an HDAC‐independent manner via the JAK‐STAT3 signaling pathway in the Schwann cells of DPN.—Du, W., Wang, N., Li, F. Jia, K., An, J., Liu, Y., Wang, Y., Zhu, L., Zhao, S. Hao, J. STAT3 phosphorylation mediates high glucose—impaired cell autophagy in an HDAC1‐dependent and ‐independent manner in Schwann cells of diabetic peripheral neuropathy. FASEB J. 33, 8008–8021 (2019). http://www.fasebj.org

Inhibiting vascular endothelial foam is the focus of clinical attention. Using SonoVue (an ultrasound contrast agent), the salusin-α gene was transfected into the arterial intima of an atherosclerotic rabbit model induced by a high-fat diet in this study. Subsequently the model of blood lipid indexes, the pathological structure of the intima, and changes in molecules regulating atherosclerosis were investigated. The high-density lipoprotein C and apolipoprotein A values in the salusin-α gene overexpression (P) group were higher than those in the salusin-α gene interference (RP) group (P < 0.05), whereas the total cholesterol, low-density lipoprotein C, and apolipoprotein B values were reversed. Rabbits in the P group showed significantly thinner vascular intimal thickness than that of other experimental groups (P < 0.05). The expression of positive regulators of atherosclerosis (ABCA1, ABCG1) was higher in the P group than that in the RP group (P < 0.05), and the opposite effect was observed for negative regulators (ACAT1, CD36). Thus, our results showed that the overexpression of salusin-α gene inhibited the proliferation of the vascular intima, thereby throwing some light on understanding the mechanism how salusin-α gene expression interfered with the foaming of vascular intimal cells.

Background IL-35–producing Bregs and Treg cells critically regulate chronic illnesses worldwide via mechanisms related to disrupting the gut microbiota composition. However, whether the gut microbiota regulates these IL-35+ cells remains elusive. We herein investigated the regulatory effects of the gut microbiota on IL-35+ cells by using genetically modified mouse models of obesity. Results We first found that gut Reg4 promoted resistance to high-fat diet-induced obesity. Using 16S rRNA sequencing combined with LC-MS (liquid chromatography–mass spectrometry)/MS, we demonstrated that gut Reg4 associated with bacteria such as Lactobacillus promoted the generation of IL-35+ B cells through 3-idoleacetic acid (IAA) in the presence of LPS. HuREG4IECtg mice fed a high-fat diet exhibited marked IL-35+ cell accumulation in not only their adipose tissues but also their colons, whereas decreased IL-35+ cell accumulation was observed in the adipose and colon tissues of Reg4 knockout (KO) mice. We also found that Reg4 mediated HFD-induced obesity resistance via IL-35. Lower levels of IAA were also detected in the peripheral blood of individuals with obesity compared with nonobese subjects. Mechanistically, IAA together with LPS mediated IL-35+ B cells through PXR and TLR4. KO of PXR or TLR4 impaired the generation of IL-35+ B cells. Conclusion Together, IAA and LPS induce the generation of IL-35+ B cells through PXR and TLR4.

The pathogenesis of inflammatory bowel disease (IBD) might be related to the local inflammatory damage and the dysbacteriosis of intestinal flora. Probiotics can regulate the intestinal flora and ameliorate IBD. The probiotic Bacillus subtilis strain B. subtilis JNFE0126 was used as the starter of fermented milk. However, the therapeutic effects of B. subtilis-fermented milk on IBD remain to be explored. In this research, the therapeutic effect of B. subtilis-fermented milk on dextran sulfate sodium salt (DSS)-induced IBD mouse model was evaluated. Besides, the expression of pro-inflammatory/anti-inflammatory cytokines, the proliferation of the intestinal stem cells, and the reconstruction of the mucosa barrier were investigated. Finally, alteration of the gut microbiota was investigated by taxonomic analysis. As shown by the results, the disease activity index (DAI) of IBD was significantly decreased through oral administration of B. subtilis (JNFE0126)-fermented milk, and intestinal mucosa injury was attenuated. Moreover, B. subtilis could reduce the inflammatory response of the intestinal mucosa, induce proliferation of the intestinal stem cell, and promote reconstruction of the mucosal barrier. Furthermore, B. subtilis could rebalance the intestinal flora, increasing the abundance of Bacillus, Alistipes, and Lactobacillus while decreasing the abundance of Escherichia and Bacteroides. In conclusion, oral administration of the B. subtilis-fermented milk could alleviate DSS-induced IBD via inhibition of inflammatory response, promotion of the mucosal barrier reconstruction, and regulation of the intestinal flora.

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Mycoplasma infection has been reported in immunocompromised cancer patients; nevertheless, it is not clear if persistent Mycoplasma infection could facilitate the proliferation of cancer cells in immunocompromised organisms. The aim of this study was to examine the relationship between persistent Mycoplasma infection and malignant transformation in an immunodeficient host model. Immunodeficient mouse model was established using cyclophosphamide and mice gastric mucosal cells were infected with Mycoplasma penetrans (Mpe). After 18 weeks, mice were sacrificed and gastric mucosal Mpe infected cells were identified by fluorescence in situ hybridization (FISH). Moreover, pathological and ultrastructural changes in mice gastric mucosa were evaluated and the expression of multiple proto-oncogenes was examined by Western blot. Our data show that Mpe infection was detected in the blood of immunodeficient mice and Mpe persistent infection in mice gastric mucosa was confirmed by FISH. There were pathological and ultrastructural malignant transformation occurred in the gastric mucosa of infected mice compared to control mice. Mpe infected mice showed lower expression of p53 and p21 and higher H-ras expression compared to the control group. Moreover, expression of NF-κB p65 subunit increased in Mpe infected mice, similar to the TNF-α expression. Bax expression in gastric mucosa of Mpe infected mice was lower while Bcl-2 expression was higher than in the uninfected control group. Collectively these data demonstrate that persistent Mpe infection is associated with aberrant expression of multiple proto-oncogenes in gastric mucosa of immunodeficient mice which potentially facilitate the malignant transformation.