A ß-1,3/1,6-glucan enhances anti-tumor effects of PD1 antibody by reprogramming tumor microenvironment.

Checkpoint blockades have emerged as a frontline approach in cancer management, designed to enhance the adaptive immune response against tumors. However, its clinical efficacy is limited to a narrow range of tumor types, which necessitates the exploration of novel strategies that target another main branch of the immune system. One such potential strategy is the therapeutic modulation of pattern recognition receptors (PRRs) pathways in innate immune cells, which have shown promise in tumor eradication. Previously, a ß-1,3/1,6-glucan with high purity from Durvillaea antarctica (BG136) was reported by our group to exhibit pan-antitumor effects. In the current study, we systemically studied the antitumor activity of BG136 in combination with anti-PD1 antibody in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggested that BG136 enhances the antitumor immunity of anti-PD1 antibody by reprogramming the tumor microenvironment to become more proinflammatory. In addition, an increase in innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, and a decreased in ascorbate and aldarate metabolism were also found. These findings provide mechanistic insights that support the potent antitumor efficacy of BG136 when combined with immune checkpoint inhibitor antibodies.

Glycopolymer with Sulfated Fucose and 6'-Sialyllactose as a Dual-Targeted Inhibitor on Resistant Influenza A Virus Strains.

The frequent mutations of influenza A virus (IAV) have led to an urgent need for the development of innovative antiviral drugs. Glycopolymers offer significant advantages in biomedical applications owing to their biocompatibility and structural diversity. However, the primary challenge lies in the design and synthesis of well-defined glycopolymers to precisely control their biological functionalities. In this study, functional glycopolymers with sulfated fucose and 6'-sialyllactose were successfully synthesized through ring-opening metathesis polymerization and a postmodification strategy. The optimized heteropolymer exhibited simultaneous targeting of hemagglutinin and neuraminidase on the surface of IAV, as evidenced by MU-NANA assay and hemagglutination inhibition data. Antiviral experiments demonstrated that the glycopolymer displayed broad and efficient inhibitory activity against wild-type and mutant strains of H1N1 and H3N2 subtypes in vitro, thereby establishing its potential as a dual-targeted inhibitor for combating IAV resistance.

Structural Elucidation of Glycosaminoglycans in the Tissue of Flounder and Isolation of Chondroitin Sulfate C.

Glycosaminoglycans (GAGs) are valuable bioactive polysaccharides with promising biomedical and pharmaceutical applications. In this study, we analyzed GAGs using HPLC-MS/MS from the bone (B), muscle (M), skin (S), and viscera (V) of Scophthalmus maximus (SM), Paralichthysi (P), Limanda ferruginea (LF), Cleisthenes herzensteini (G), Platichthys bicoloratus (PB), Pleuronichthys cornutus (PC), and Cleisthenes herzensteini (CH). Unsaturated disaccharide products were obtained by enzymatic hydrolysis of the GAGs and subjected to compositional analysis of chondroitin sulfate (CS), heparin sulfate (HS), and hyaluronic acid (HA), including the sulfation degree of CS and HS, as well as the content of each GAG. The contents of GAGs in the tissues and the sulfation degree differed significantly among the fish. The bone of S. maximus contained more than 12 µg of CS per mg of dry tissue. Although the fish typically contained high levels of CSA (CS-4S), some fish bone tissue exhibited elevated levels of CSC (CS-6S). The HS content was found to range from 10-150 ug/g, primarily distributed in viscera, with a predominant non-sulfated structure (HS-0S). The structure of HA is well-defined without sulfation modification. These analytical results are independent of biological classification. We provide a high-throughput rapid detection method for tissue samples using HPLC-MS/MS to rapidly screen ideal sources of GAG. On this basis, four kinds of CS were prepared and purified from flounder bone, and their molecular weight was determined to be 23-28 kDa by HPGPC-MALLS, and the disaccharide component unit was dominated by CS-6S, which is a potential substitute for CSC derived from shark cartilage.

Immune-enhancing activity of compound polysaccharide on the inactivated influenza vaccine.

Traditional Chinese medicine polysaccharides have numerous biological activities with broad applications in the biomedical industries. However, a clear understanding of the pharmacological activities of compound polysaccharides with multi-component structures remain challenging. This study aimed to investigate the immune boosting effect of compound polysaccharides on the influenza vaccine and assess the preliminary structure-activity relationship. The compound polysaccharide (CP) was isolated from the combined Chinese herbs lentinan, pachymaran and tremellan, and purified by gradient ethanol precipitation to obtain its subcomponents of CP-20, CP-40, CP-60, and CP-80 with decreasing molecular weights. These polysaccharides were mainly composed of glucans with different linkage patterns, including α-(1 â†’ 3)-glucan, α-(1 â†’ 4)-glucan and ß-(1 â†’ 6)-glucan. A significant improvement was observed in the survival of mice vaccinated with inactivated (IAV) vaccine and the isolated polysaccharides as adjuvants. A reduction in the pulmonary virus titer and weight loss were also observed. Moreover, CP-40 and CP-60, as well as the original CP, significantly enhanced the serum anti-IAV antibody titers and interleukin IL-2, IL-5, and IL-6 concentrations. These preliminary results indicate the immune boosting effect of the compound polysaccharides is highly relevant to the specific structural properties of the subcomponent, and CP-40 is worthy of further exploration as a glycan adjuvant for the IAV vaccine.

Degradation and fermentation of hyaluronic acid by Bacteroides spp. from the human gut microbiota.

Bacteroides spp. are prominent members of the human gut microbiota that play critical roles in the metabolism of complex carbohydrates from the daily diet. Hyaluronic acid (HA) is a multifunctional polysaccharide which has been extensively used in the food and biomedical industry. However, how HA is degraded and fermented by Bacteroides spp. has not been fully characterized. Here, we comprehensively investigated the detailed degradation profiles and fermentation characteristics of four different HAs with discrete molecular weight (Mw) by fourteen distinctive Bacteroides spp. from the human gut microbiota. Our results indicated that high-Mw HAs were more degradable and fermentable than low-Mw HAs. Interestingly, B. salyersiae showed the best degrading capability for both high-Mw and low-Mw HAs, making it a keystone species for HA degradation among Bacteroides spp.. Specifically, HA degradation by B. salyersiae produced significant amounts of unsaturated tetrasaccharide (udp4). Co-culture experiments indicated that the produced udp4 could be further fermented and utilized by non-proficient HA-degraders, suggesting a possible cross-feeding interaction in the utilization of HA within the Bacteroides spp.. Altogether, our study provides novel insights into the metabolism of HA by the human gut microbiota, which has considerable implications for the development of new HA-based nutraceuticals and medicines.

Bacteroides salyersiae is a potent chondroitin sulfate-degrading species in the human gut microbiota.

Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS could not be absorbed after oral intake due to its polyanionic nature and large molecular weight. Gut microbiota has recently been proposed to play a pivotal role in the metabolism of drugs and nutrients. Nonetheless, how CS is degraded by the human gut microbiota has not been fully characterized. In the present study, we demonstrated that each human gut microbiota was characterized with a unique capability for CS degradation. Degradation and fermentation of CS by the human gut microbiota produced significant amounts of unsaturated CS oligosaccharides (CSOSs) and short-chain fatty acids. To uncover which microbes were responsible for CS degradation, we isolated a total of 586 bacterial strains with a potential CS-degrading capability from 23 human fecal samples. Bacteroides salyersiae was a potent species for CS degradation in the human gut microbiota and produced the highest amount of CSOSs as compared to other well-recognized CS-degraders, including Bacteroides finegoldii, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, and Bacteroides ovatus. Genomic analysis suggested that B. salyersiae was armed with multiple carbohydrate-active enzymes that could potentially degrade CS into CSOSs. By using a spent medium assay, we further demonstrated that the unsaturated tetrasaccharide (udp4) produced by the primary degrader B. salyersiae could serve as a "public goods" molecule for the growth of Bacteroides stercoris, a secondary CS-degrader that was proficient at fermenting CSOSs but not CS. Taken together, our study provides insights into the metabolism of CS by the human gut microbiota, which has promising implications for the development of medical and nutritional therapies for osteoarthritis. Video Abstract.

Immobilization of ferrocene and its derivatives within metal-organic frameworks with high loadings toward efficient oxygen evolution reaction.

The use of an appropriate preparation route is the key to immobilize active molecules into a host matrix with high loadings and stability. Herein, we demonstrate a simple and general strategy to immobilize ferrocene and its derivatives into ZIF-8 with high loadings of up to 4.3% Fe content. The unique host pore structure allows for the stabilization of guest molecules and effectively prevents their leaching. As a result, the obtained electrocatalysts exhibit competitive oxygen evolution reaction (OER) catalytic performance. Optimized Fc-CHO/ZIF-8 requires only a low overpotential of 238 mV to achieve 10 mA cm-2, along with a relatively small Tafel slope of 44.4 mV dec-1. This performance is superior to that of commercial IrO2, suggesting its potential application in electrochemical energy conversion.

Biodegradable chitosan­zirconium composite adsorptive membranes for potential arsenic (III/V) capture electrodialysis.

Combining adsorption with other technologies holds great potential in fast and deep arsenic ion removal. Herein, chitosan­zirconium composite adsorptive membranes (CS-Zr CM) were successfully prepared using simple casting and sodium hydroxide coagulation strategies, which was demonstrated the use in arsenic ion-capture electrodialysis based on their good adsorption performance. In the batch adsorption tests, the maximum adsorption capacities of CS-Zr CM for As(III) and As(V) were 134.2 mg/g and 119.5 mg/g, respectively. CS-Zr CM also exhibited satisfying adsorption selectivity and good reusability toward As(III) and As(V). However, the adsorption kinetics showed that they needed 48 h to reach the adsorption equilibrium and the adsorption ability toward trace arsenic ion was ineffective. Furthermore, CS-Zr CM was applied as the adsorptive membrane in the electrodialysis process. Under the influence of electric field, the As(III) and As(V) removal equilibrium time was shortened to 12 h and the concentrations of As(III) and As(V) ions could be efficiently reduced to below the WHO limit in drinking water (10 µg/L), which far surpassed the physicochemical adsorption method. Such good arsenic ion removal ability of CS-Zr CM together with the ease scalable fabrication, low cost, and biodegradable properties shows its huge prospects in arsenic-containing wastewater treatment.

Polyguluronate alleviates ulcerative colitis by targeting the gut commensal Lactobacillus murinus and its anti-inflammatory metabolites.

Polyguluronate (PG) is a fermentable polysaccharide from edible algae. The present study was designed to investigate the therapeutic effect of PG on ulcerative colitis (UC) and its underlying mechanisms. Our results suggest that oral intake of PG attenuates UC and improves gut microbiota dysbiosis by promoting the growth of Lactobacillus spp. in dextran sulfate sodium-fed mice. Five different species of Lactobacillus were isolated from the feces of PG-treated mice and L. murinus was identified to have the best anti-colitis effect, suggesting a critical role for L. murinus in mediating the therapeutic effect of PG. Furthermore, PG was degraded potentially by the beta-glucuronidase from L. murinus and adding PG to the culture medium of L. murinus remarkably increased its production of anti-inflammatory metabolites, including itaconic acid, cis-11,14-eicosadienoic acid, and 3-amino-3-(2-chlorophenyl)-propionic acid. Additionally, L. salivarius, a human intestine-derived PG-utilizing species that is closely related to L. murinus, was also demonstrated to have potent anti-colitis effects, suggesting that it is a candidate target of PG in the human gut. Altogether, our study illustrates an unprecedented application of PG in the treatment of UC and establishes the basis for understanding its therapeutic effect from the perspective of L. murinus and its metabolites.

Serum-based Comprehensive N-Glycans Profiling Analysis in Different Gastric Disease Stages by Porous Graphitic Carbon Liquid Chromatography-Mass Spectrometry Associated With Potential Marker Discovery.

BACKGROUND/AIM: N-glycans are potential serum biomarkers due to their aberrant structure and abundance alteration during disease progression. Few studies have been associated with relative quantitative N-glycans profiling during different gastric disease stages. In this study, we conducted an investigation on the profiling of N-glycans in patients with gastric disease, as well as in healthy controls. MATERIALS AND METHODS: In this study, the porous graphitization carbon chromatography-high resolution Fourier transform mass spectrometry (PGC-FTMS) method was applied to assess comprehensive N-glycans profiling in patients at different stages of gastric disease, including gastritis, atrophic gastritis, gastric ulcer, gastric polyps, and gastric cancer. RESULTS: A total of 45 N-glycans (relative abundance >0.1%) were detected, and 9 N-glycans were found to be potential biomarkers for gastric disease detection. Along with the progression of gastric disease, the abundance of sialylated N-glycans increased, while that of core-fucosylated N-glycans decreased. Multivariate statistical analysis demonstrated that N-glycans profiling between gastritis and healthy controls had significant differences. The characteristic N-glycans distinguished gastric cancer from healthy controls, which had strong clinical diagnostic value. CONCLUSION: The relative quantitative profile of N-glycans in different gastric disease stages was revealed and serum N-glycans are proposed for distinguishing gastric disease stages in clinical application.

In Vitro Fermentation of Polysaccharide from Edible Alga Enteromorpha clathrata by the Gut Microbiota of Patients with Ulcerative Colitis.

Dietary intake of the sulfated polysaccharide from edible alga E. clathrata (ECP) has recently been illustrated to attenuate ulcerative colitis (UC) by targeting gut dysbiosis in mice. However, ECP is not easily absorbed in the gut and, as a potential candidate for next-generation prebiotics development, how it is fermented by human gut microbiota has not been characterized. Here, using in vitro anaerobic fermentation and 16S high-throughput sequencing, we illustrate for the first time the detailed fermentation characteristics of ECP by the gut microbiota of nine UC patients. Our results indicated that, compared to that of glucose, fermentation of ECP by human gut microbiota produced a higher amount of anti-inflammatory acetate and a lower amount of pro-inflammatory lactate. Additionally, ECP fermentation helped to shape a more balanced microbiota composition with increased species richness and diversity. Moreover, ECP significantly stimulated the growth of anti-colitis bacteria in the human gut, including Bacteroides thetaiotaomicron, Bacteroides ovatus, Blautia spp., Bacteroides uniformis, and Parabacteroides spp. Altogether, our study provides the first evidence for the prebiotic effect of ECP on human gut microbiota and sheds new light on the development of ECP as a novel prebiotic candidate for the prevention and potential treatment of UC.

Discovery of Bacteroides uniformis F18-22 as a Safe and Novel Probiotic Bacterium for the Treatment of Ulcerative Colitis from the Healthy Human Colon.

Previous studies have demonstrated that the intestinal abundance of Bacteroides uniformis is significantly higher in healthy controls than that in patients with ulcerative colitis (UC). However, what effect B. uniformis has on the development of UC has not been characterized. Here, we show for the first time that B. uniformis F18-22, an alginate-fermenting bacterium isolated from the healthy human colon, protects against dextran-sulfate-sodium (DSS)-induced UC in mice. Specifically, oral intake of B. uniformis F18-22 alleviated colon contraction, improved intestinal bleeding and attenuated mucosal damage in diseased mice. Additionally, B. uniformis F18-22 improved gut dysbiosis in UC mice by increasing the abundance of anti-inflammatory acetate-producing bacterium Eubacterium siraeum and decreasing the amount of pro-inflammatory pathogenetic bacteria Escherichia-Shigella spp. Moreover, B. uniformis F18-22 was well-tolerated in mice and showed no oral toxicity after repeated daily administration for 28 consecutive days. Taken together, our study illustrates that B. uniformis F18-22 is a safe and novel probiotic bacterium for the treatment of UC from the healthy human colon.

The reason and mechanism of propylene glycol alginate sodium sulfate (PSS) mediated allergic side effect.

Propylene glycol alginate sodium sulfate (PSS) is a heparinoid polysaccharide drug used in clinic for >30 years in China. But its allergy events happened from time to time and should not be ignored. Here, ammonium salt in PSS (PSS-NH4+), PSS fractions with high Mw (PSS-H-Mw) and low mannuronic acid (M) to guluronic acid (G) ratio (PSS-L-M/G) were found to induce allergic response by the structure-activity and impurity-activity relationships in vitro. Furthermore, we confirmed the reason and elucidated the mechanism accounted for allergic side effect of PSS in vivo. It was found that high IgE levels in PSS-NH4+ and PSS-H-Mw groups upregulate the cascade expression of Lyn-Syk-Akt or Erk and second messenger Ca2+, which accelerated mast cells (MCs) degranulation to release histamine, LTB4, TPS, and finally induced lung tissue injury. PSS-L-M/G caused a mild allergic symptom because it only enhanced the expression of p-Lyn and histamine release. In brief, PSS-NH4+ and PSS-H-Mw were main reasons to result in allergic response. Our results suggested that it is very necessary to control the range of Mw and the content of impurities (< 1 % ammonium salt) of PSS to guarantee its safety and effectiveness in clinical treatment.

Isolation of Alginate-Degrading Bacteria from the Human Gut Microbiota and Discovery of Bacteroides xylanisolvens AY11-1 as a Novel Anti-Colitis Probiotic Bacterium.

Alginate has been documented to prevent the development and progression of ulcerative colitis by modulating the gut microbiota. However, the bacterium that may mediate the anti-colitis effect of alginate has not been fully characterized. We hypothesized that alginate-degrading bacteria might play a role here since these bacteria could utilize alginate as a carbon source. To test this hypothesis, we isolated 296 strains of alginate-degrading bacteria from the human gut. Bacteroides xylanisolvens AY11-1 was observed to have the best capability for alginate degradation. The degradation and fermentation of alginate by B. xylanisolvens AY11-1 produced significant amounts of oligosaccharides and short-chain fatty acids. Further studies indicated that B. xylanisolvens AY11-1 could alleviate body weight loss and contraction of colon length, reduce the incidences of bleeding and attenuate mucosal damage in dextran sulfate sodium (DSS)-fed mice. Mechanistically, B. xylanisolvens AY11-1 improved gut dysbiosis and promoted the growth of probiotic bacteria, including Blautia spp. And Prevotellaceae UCG-001, in diseased mice. Additionally, B. xylanisolvens AY11-1 showed no oral toxicity and was well-tolerated in male and female mice. Altogether, we illustrate for the first time an anti-colitis effect of the alginate-degrading bacterium B. xylanisolvens AY11-1. Our study paves the way for the development of B. xylanisolvens AY11-1 as a next-generation probiotic bacterium.

Fucoidan from Fucus vesiculosus prevents the loss of dopaminergic neurons by alleviating mitochondrial dysfunction through targeting ATP5F1a.

Parkinson's disease is a neurodegenerative disease that is characterized by the loss of dopaminergic neurons. Fucoidan, which has emerged as a neuroprotective agent, is a marine-origin sulfated polysaccharide enriched in brown algae and sea cucumbers. However, variations in structural characteristics exist among fucoidans derived from different sources, resulting in a wide spectrum of biological effects. It is urgent to find the fucoidan with the strongest neuroprotective effect, and the mechanism needs to be further explored. We isolated and purified four different fucoidan species with different chemical structures and found that Type II fucoidan from Fucus vesiculosus (FvF) significantly improved mitochondrial dysfunction, prevented neuronal apoptosis, reduced dopaminergic neuron loss, and improved motor deficits in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Further mechanistic investigation revealed that the ATP5F1a protein is a key target responsible for alleviating mitochondrial dysfunction of FvF to exert neuroprotective effects. This study highlights the favorable properties of FvF for neuroprotection, making FvF a promising candidate for the treatment of PD.

Polysaccharide from Edible Alga Enteromorpha clathrata Improves Ulcerative Colitis in Association with Increased Abundance of Parabacteroides spp. in the Gut Microbiota of Dextran Sulfate Sodium-Fed Mice.

Polysaccharide from the edible alga Enteromorpha clathrata has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we illustrate that Enteromorpha clathrata polysaccharide (ECP) could alleviate body weight loss, reduce incidences of colonic bleeding, improve stool consistency and ameliorate mucosal damage in diseased mice. 16S rRNA high-throughput sequencing and bioinformatic analysis indicated that ECP significantly changed the structure of the gut microbiota and increased the abundance of Parabacteroides spp. in DSS-fed mice. In vitro fermentation studies further confirmed that ECP could promote the growth of Parabacteroides distasonis F1-28, a next-generation probiotic bacterium isolated from the human gut, and increase its production of short-chain fatty acids. Additionally, Parabacteroides distasonis F1-28 was also found to have anti-ulcerative colitis effects in DSS-fed mice. Altogether, our study demonstrates for the first time a beneficial effect of ECP on ulcerative colitis and provides a possible basis for understanding its therapeutic mechanisms from the perspective of symbiotic gut bacteria Parabacteroides distasonis.

Exopolysaccharides from Marine Microbes: Source, Structure and Application.

The unique living environment of marine microorganisms endows them with the potential to produce novel chemical compounds with various biological activities. Among them, the exopolysaccharides produced by marine microbes are an important factor for them to survive in these extreme environments. Up to now, exopolysaccharides from marine microbes, especially from extremophiles, have attracted more and more attention due to their structural complexity, biodegradability, biological activities, and biocompatibility. With the development of culture and separation methods, an increasing number of novel exopolysaccharides are being found and investigated. Here, the source, structure and biological activities of exopolysaccharides, as well as their potential applications in environmental restoration fields of the last decade are summarized, indicating the commercial potential of these versatile EPS in different areas, such as food, cosmetic, and biomedical industries, and also in environmental remediation.

Comparative Proteomic Analysis of Fucosylated Glycoproteins Produced by Bacteroides thetaiotaomicron Under Different Polysaccharide Nutrition Conditions.

Bacteroides thetaiotaomicron, one of the most eminent representative gut commensal Bacteroides species, is able to use the L-fucose in host-derived and dietary polysaccharides to modify its capsular polysaccharides and glycoproteins through a mammalian-like salvage metabolic pathway. This process is essential for the colonization of the bacteria and for symbiosis with the host. However, despite the importance of fucosylated proteins (FGPs) in B. thetaiotaomicron, their types, distribution, and functions remain unclear. In this study, the effects of different polysaccharide (corn starch, mucin, and fucoidan) nutrition conditions on newly synthesized FGPs expressions and fucosylation are investigated using a chemical biological method based on metabolic labeling and bioorthogonal reaction. According to the results of label-free quantification, 559 FGPs (205 downregulated and 354 upregulated) are affected by the dietary conditions. Of these differentially expressed proteins, 65 proteins show extremely sensitive to polysaccharide nutrition conditions (FGPs fold change/global protein fold change ≥2.0 or ≤0.5). Specifically, the fucosylation of the chondroitin sulfate ABC enzyme, Sus proteins, and cationic efflux system proteins varies significantly upon the addition of mucin, corn starch, or fucoidan. Moreover, these polysaccharides can trigger an appreciable increase in the fucosylation level of the two-component system and ammonium transport proteins. These results highlight the efficiency of the combined metabolic glycan labeling and bio-orthogonal reaction in enriching the intestinal Bacteroides glycoproteins. Moreover, it emphasizes the sensitivity of Bacteroides fucosylation to polysaccharide nutrition conditions, which allows for the regulation of bacterial growth.

Canagliflozin Prevents Lipid Accumulation, Mitochondrial Dysfunction, and Gut Microbiota Dysbiosis in Mice With Diabetic Cardiovascular Disease.

Type 2 diabetes mellitus (T2DM) is associated with cardiovascular disease (CVD) and sodium glucose cotransporter 2 inhibitors, as oral medications for T2DM treatment have shown the potential to improve vascular dysfunction. The aim of this study was to evaluate the ability of canagliflozin (Cana) to relieve CVD in T2DM mice and its possible action mechanism. Mice with diabetic CVD was conducted by a high-fat diet for 24 weeks, followed by oral gavaging with metformin (200 mg/kg/day) or Cana (50 mg/kg/day) for 6 weeks. The result demonstrated that Cana reduced serum lipid accumulation, and decreased the arteriosclerosis index and atherogenic index of plasma. In addition, Cana treatment reduced the circulating markers of inflammation. More importantly, Cana improved cardiac mitochondrial homeostasis and relieved oxidative stress. Moreover, Cana treatment alleviated the myocardial injury with decreasing levels of serous soluble cluster of differentiation 40 ligand and cardiac troponin I. Thus, cardiovascular abnormality was relieved by suppressing fibrosis and basement membrane thickening, while elevating the cluster of differentiation 31 expression level. Importantly, Cana increased the ratio of gut bacteria Firmicutes/Bacteroidetes and the relative abundance of Alistipes, Olsenella, and Alloprevotella, while it decreased the abundance of Mucispirillum, Helicobacter, and Proteobacteria at various taxonomic levels in mice with diabetic CVD. In short, Cana treatment altered the colonic microbiota composition close to the normal level, which was related with blood lipid, inflammation, and oxidative stress, and might play a vital role in CVD. In general, the improvements in the gut microbiota and myocardial mitochondrial homeostasis may represent the mechanism of Cana on CVD treatment.

Eupatilin Suppresses OVA-Induced Asthma by Inhibiting NF-κB and MAPK and Activating Nrf2 Signaling Pathways in Mice.

To investigate the effect of eupatilin in asthma treatment, we evaluated its therapeutic effect and related signal transduction in OVA-induced asthmatic mice and LPS-stimulated RAW264.7 cells. The BALF was tested for changes in lung inflammatory cells. Th2 cytokines in the BALF and OVA-IgE in the serum were measured by ELISA. H&E and PAS staining were used to evaluate histopathological changes in mouse lungs. The key proteins NF-κB, MAPK, and Nrf2 in lung tissues were quantitatively analyzed by Western blotting. Finally, we evaluated the effect of eupatilin on cytokines and related protein expression in LPS-stimulated RAW 264.7 cells in vitro. In OVA-induced asthmatic mice, eupatilin reduced the numbers of inflammatory cells, especially neutrophils and eosinophils. Eupatilin also decreased the levels of IL-5, IL-13 in the BALF and OVA-IgE in the serum. Furthermore, eupatilin inhibited the activation of NF-κB and MAPK pathways and increased the expression of Nrf2 in OVA-induced asthmatic mice. In vitro, eupatilin significantly reduced LPS-stimulated NO, IL-6, and ROS production. Additionally, the NF-κB, MAPK, and Nrf2 protein expression in LPS-stimulated RAW264.7 cells was consistent with that in OVA-induced asthmatic lung tissues. In summary, eupatilin attenuated OVA-induced asthma by regulating NF-κB, MAPK, and Nrf2 signaling pathways. These results suggest the utility of eupatilin as an anti-inflammatory drug for asthma treatment.