Correction: Zhang et al. Fucoidan from Laminaria japonica Ameliorates Type 2 Diabetes Mellitus in Association with Modulation of Gut Microbiota and Metabolites in Streptozocin-Treated Mice. Foods 2023, 12, 33.

In the original publication, there was a mistake in Figure 3 as published [...].

Scytosiphon lomentaria fucoidan ameliorates DSS-induced colitis in dietary fiber-deficient mice via modulating the gut microbiota and inhibiting the TLR4/NF-κB/MLCK pathway.

The prevalence of ulcerative colitis (UC) poses a serious threat to human health. This study showed that fiber-deficient diet (FD) increased the susceptibility of mice to low dosage of DSS-induced UC, and a UC model was established by feeding mice with DSS and FD to evaluate the effect of Scytosiphon lomentaria fucoidan (SLF) on UC. SLF ameliorated the symptoms of UC, as evidenced by increases in colon length, goblet cells and glycoprotein and reduction in inflammatory cell infiltration and intestinal epithelial injury. SLF alleviated oxidative stress and inhibited colonic inflammation by reducing the levels of lipopolysaccharides and pro-inflammatory cytokines and suppressing the activation of nuclear factor kappa B pathway. SLF protected tight junction integrity by reducing the level of myosin light chain kinase and increasing the levels of claudin, zonula occludens-1 and occludin. SLF improved serum metabolites profile and affected multiple metabolic pathways that are crucial to human health, e.g. butanoate metabolism. The underlying mechanism can be associated with modulation of the gut microbiota and metabolites, including increases in short chain fatty acids and reduction in Proteobacteria, Bacteroides and Romboutsia. It suggests that SLF could be developed as a prebiotic polysaccharide to benefit human health by improving intestinal microecology.

Undaria pinnatifida fucoidan contributes to anti-inflammation activity of Bacteroides in fiber-deficient mice via modulation of gut microbiota and protection of intestinal barrier integrity.

Bacteroides as potential probiotics has several health benefits to the host, but its practical application faces many challenges due to its inherent properties. In this study, Bacteroides strains isolated from human feces alleviated colonic inflammation in mice, as evidenced by increased colon length and reduced tissue damage. Further study showed that anti-inflammation activity of Bacteroides strains was disturbed by dietary fiber deficiency (FD), which disrupted the balance between gut microbiota and colonic mucus layer, leading to a thinning of colonic mucus layer. A combination of Bacteroides strains and Undaria pinnatifida fucoidan (UPF) better alleviated colonic inflammation than either of them, including increases in the densities of goblet cells and glycoproteins and reduction in intestinal epithelial damage, pro-inflammatory cytokines and oxidative stress. The underlying mechanisms can be attributed to that UPF-induced alterations of mucosal microbiota cannot only directly benefit host health but also create an ecological condition that facilitates Bacteroides strains exert their healthy properties. In addition, both Bacteroides strains and UPF improved FD-induced lipid metabolism abnormality, mainly involving glycerophospholipid metabolism pathway. This study suggests that the application of Bacteroides has certain limitations, and UPF can be developed as a probiotic adjuvant for Bacteroides to enhance human health.

Undaria pinnatifida fucoidan ameliorates dietary fiber deficiency-induced inflammation and lipid abnormality by modulating mucosal microbiota and protecting intestinal barrier integrity.

Dietary fiber deficiency (FD) is a new public health concern, with limited understanding of its impact on host energy requirements and health. In this study, the effect of fucoidan from Undaria pinnatifida (UPF) on FD-induced alterations of host physiological status was analyzed in mice. UPF increased colon length and cecum weight, reduced liver index, and modulated serum lipid metabolism primarily involving glycerophospholipid and linoleic acid metabolism in FD-treated mice. UPF protected against FD-induced destruction of intestinal barrier integrity by upregulating the expression levels of tight junction proteins and mucin-related genes. UPF alleviated FD-induced intestinal inflammation by reducing the levels of inflammation-related factors, such as interleukin-1ß, tumor necrosis factor-α, and lipopolysaccharides, and relieving oxidative stress. The underlying mechanism can be closely associated with modulation of gut microbiota and metabolites, such as a reduction of Proteobacteria and an increase in short chain fatty acids. The in vitro model showed that UPF mitigated H2O2-induced oxidative stress and apoptosis in IEC-6 cells, indicating its potential as a therapeutic agent for inflammatory bowel disorders. This study suggests that UPF can be developed as a fiber supplement to benefit host health by modulating gut microbiota and metabolites and protecting intestinal barrier functions.

Hydrogen attenuates postoperative pain through Trx1/ASK1/MMP9 signaling pathway.

BACKGROUND: Postoperative pain is a serious clinical problem with a poorly understood mechanism, and lacks effective treatment. Hydrogen (H2) can reduce neuroinflammation; therefore, we hypothesize that H2 may alleviate postoperative pain, and aimed to investigate the underlying mechanism. METHODS: Mice were used to establish a postoperative pain model using plantar incision surgery. Mechanical allodynia was measured using the von Frey test. Cell signaling was assayed using gelatin zymography, western blotting, immunohistochemistry, and immunofluorescence staining. Animals or BV-2 cells were received with/without ASK1 and Trx1 inhibitors to investigate the effects of H2 on microglia. RESULTS: Plantar incision surgery increased MMP-9 activity and ASK1 phosphorylation in the spinal cord of mice. MMP-9 knockout and the ASK1 inhibitor, NQDI-1, attenuated postoperative pain. H2 increased the expression of Trx1 in the spinal cord and in BV-2 cells. H2 treatment mimicked NQDI1 in decreasing the phosphorylation of ASK1, p38 and JNK. It also reduced MMP-9 activity, downregulated pro-IL-1ß maturation and IBA-1 expression in the spinal cord of mice, and ameliorated postoperative pain. The protective effects of H2 were abolished by the Trx1 inhibitor, PX12. In vitro, in BV-2 cells, H2 also mimicked NQDI1 in inhibiting the phosphorylation of ASK1, p38, and JNK, and also reduced MMP-9 activity and decreased IBA-1 expression induced by LPS. The Trx1 inhibitor, PX12, abolished the protective effects of H2 in BV-2 cells. CONCLUSIONS: For the first time, the results of our study confirm that H2 can be used as a therapeutic agent to alleviate postoperative pain through the Trx1/ASK1/MMP9 signaling pathway. MMP-9 and ASK1 may be the target molecules for relieving postoperative pain.

Fucoidan from Scytosiphon lomentaria protects against destruction of intestinal barrier, inflammation and lipid abnormality by modulating the gut microbiota in dietary fibers-deficient mice.

Inadequate dietary fibers intake has been a threat for public health, and its adverse effect and regulatory mechanisms remain unclear. In this study, the protective effect of fucoidan from Scytosiphon lomentaria (SLF) on dietary fibers deficiency (FF)-induced change of physiological functions was analyzed in mice. SLF reduced weight gain and low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol, but had no effect on food intake and body fat mass in FF-treated mice. Lipidomics analysis showed that SLF modulated lipid metabolism, mainly involving glycerophospholipid and linolenic acid metabolism pathways. In addition, SLF protected against FF-induced colon damages, including the integrity of epithelial cell layer, loss of goblet cells, crypts and glycoproteins, and inflammatory cells infiltration. The underlying mechanisms can be associated with inhibition of oxidative stress, increase of tight junction proteins, and regulation of cytokines profile via nuclear factor kappa B pathway. On the other hand, SLF modulated FF-induced gut microbiota dysbiosis that had close relation with host physiological functions, e.g. increases in Akkermansia, Parabacteroides, Bacteroides and Alistipes. It indicates that SLF can be developed as a prebiotic agent to benefit host health through protecting intestinal barrier and regulating the gut microbiota.

Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis.

Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous "inflammation brake." We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.

Polysaccharides from edible brown seaweed Undaria pinnatifida are effective against high-fat diet-induced obesity in mice through the modulation of intestinal microecology.

Brown seaweed is rich in polysaccharides including sulfated polysaccharides and alginate, both of which provide health benefits to the host but whose differences have not received sufficient attention. In this study, alginate from Undaria pinnatifida (UPA) and sulfated polysaccharides from U. pinnatifida (UPSP) were isolated, and their action was analyzed in high fat diet-fed mice. UPA and UPSP improved body composition, fat deposition in body tissues and organs, lipid abnormality and inflammatory response in mice, and compound polysaccharides from U. pinnatifida (UPP: UPA + UPSP) had a better effect on some physiological indexes, which could be attributed to the differences in the gut microbiota. Both UPSP and UPA modulated diet-induced microbiota dysbiosis, and UPP had better effect on changes in the gut microbiota, including an increase in Bacteroidales and reduction in both Clostridiales and Lactobacillales that had positive correlations with the improvement of the physiological status. The in vitro model of bacterial culture revealed that the use of Bacteroides on UPA and UPSP was species dependent, and UPP can better maintain the diversity and stability of the Bacteroidales community. This study indicated that polysaccharides from edible brown seaweed can benefit host health by improving the intestinal microecology, which can be helpful for the application of edible brown seaweed in health foods.

Fucoidan from Laminaria japonica Ameliorates Type 2 Diabetes Mellitus in Association with Modulation of Gut Microbiota and Metabolites in Streptozocin-Treated Mice.

Chronic diseases have been a leading cause of death worldwide, and polysaccharide supplementation is an effective therapeutic strategy for chronic diseases without adverse effects. In this study, the beneficial effect of Laminaria japonica fucoidan (LJF) on type 2 diabetes mellitus (T2DM) was evaluated in streptozocin-treated mice. LJF ameliorated the symptoms of T2DM in a dose-dependent manner, involving reduction in weight loss, water intake, triglyceride, blood glucose, cholesterol and free fatty acids, and increases in high-density lipoprotein cholesterol, catalase, glucagon-like peptide-1, and superoxide dismutase. In addition, LJF regulated the balance between insulin resistance and insulin sensitivity, reduced islet necrosis and ß-cell damage, and inhibited fat accumulation in T2DM mice. The protective effect of LJF on T2DM can be associated with modulation of the gut microbiota and metabolites, e.g., increases in Lactobacillus and Allobaculum. Untargeted and targeted metabolomics analysis showed that the microbiota metabolite profile was changed with LJF-induced microbiota alterations, mainly involving amino acids, glutathione, and glyoxylate and dicarboxylate metabolism pathways. This study indicates that LJF can be used as a prebiotic agent for the prevention and treatment of diabetes and microbiota-related diseases.

Sulfated polysaccharides from pacific abalone attenuated DSS-induced acute and chronic ulcerative colitis in mice via regulating intestinal micro-ecology and the NF-κB pathway.

Due to potential side effects of current drugs in colitis treatment, polysaccharides with anti-inflammatory activities can be considered as alternative molecules for colitis treatment. Sulfated polysaccharide from pacific abalone (AGSP) reduced the level of lipopolysaccharides (LPS) and increased the production of short chain fatty acids in the colon of mice, and it reduced the levels of interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α and increased the IL-10 level in in vitro cell models, suggesting that it can be used as a probiotic agent to inhibit intestinal inflammation. Furthermore, AGSP reduced the disease activity index and intestinal damage, improved the mucosal immune response, and inhibited oxidative damage in mice with DSS-induced acute and chronic colitis, which can be associated with modulation of the NF-κB signaling pathway and gut microbiota. AGSP regulated the structure of the gut microbiota and reduced the level of Bacteroides that had positive correlation with the colitis symptoms. The in vitro result showed that AGSP may inhibit mucin degradation by Bacteroides via the change of the polysaccharide utilization strategy, which can protect intestinal barrier integrity. This study is useful to understand the mechanism by which AGSP ameliorates colitis and related diseases and promotes further development of AGSP.

Low-molecular alginate improved diet-induced obesity and metabolic syndrome through modulating the gut microbiota in BALB/c mice.

Alginate is the most abundant polysaccharide in brown seaweed, which is widely used as a food additive, but its high viscosity and gel property limit its applications in foods as a functional ingredient. In this study, low-molecular alginate from Laminaria japonica (L-LJA) was prepared, and its effect on obesity and metabolic syndrome was analyzed in high-fat diet (HFD)-fed mice. L-LJA reduced weight gain, fat accumulation in the liver and epididymal adipose tissue, lipid abnormality and inflammation in HFD-fed mice accompanied with the improvement of gut microbiota. L-LJA modulated the structure of gut microbiota, increased some Bacteroidales members, and reduced some Clostridiales members in mice, which were positively correlated with the improvement of physiological status. Fecal transplant from L-LJA-fed mice reduced fat accumulation in body tissues and lipid abnormality in the serum and liver and increased short chain fatty acids production in HFD-fed mice, confirming that L-LJA-induced gut microbiota alteration played an important role in its bioactivity. L-LJA has better solubility and can be utilized in food systems in high dose, implying that it can be developed as a prebiotic agent to increase both economic value and nutritive value of alginate.

[Modified 1/3 tubular plate and lag screw for the treatment of ankle fractures in elderly patients].

OBJECTIVE: To study a kind of surgical instrument for the treatment of ankle fractures in elderly patients. METHODS: From October 2007 to May 2009, 14 patients (9 males and 5 females,ranging in age from 58 to 81 years, averaged 69.3 years) with ankle joint fractures of type A and B were treated with modified 1/3 tubular plate combined with lag screws. According to the Danis-Weber classification, 6 patients were type A and 8 patients were type B. The AOFAS criteria was used to evaluate clinical effects. RESULTS: All the patients were followed up ranged from 12 to 18 months and healed. The time of union of fractures ranged from 10 to 16 weeks. According to the clinical assess standard of AOFAS, the average score was 88.0 +/- 2.1. CONCLUSION: It is one of good choices to use modified 1/3 tubular plate and lag screws to treat ankle joint fractures in elder patients.