Metatranscriptomic Characterization of Coronavirus Disease 2019 Identified a Host Transcriptional Classifier Associated With Immune Signaling.

BACKGROUND: The recent identification of a novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2, has caused a global outbreak of respiratory illnesses. The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection. However, little is known about the metatranscriptomic characteristics of patients with coronavirus disease 2019 (COVID-19). METHODS: We analyzed metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia). Transcriptional aspects of 3 core elements, pathogens, the microbiome, and host responses, were evaluated. Based on the host transcriptional signature, we built a host gene classifier and examined its potential for diagnosing COVID-19 and indicating disease severity. RESULTS: The airway microbiome in COVID-19 patients had reduced alpha diversity, with 18 taxa of differential abundance. Potentially pathogenic microbes were also detected in 47% of the COVID-19 cases, 58% of which were respiratory viruses. Host gene analysis revealed a transcriptional signature of 36 differentially expressed genes significantly associated with immune pathways, such as cytokine signaling. The host gene classifier built on such a signature exhibited the potential for diagnosing COVID-19 (area under the curve of 0.75-0.89) and indicating disease severity. CONCLUSIONS: Compared with those with non-COVID-19 pneumonias, COVID-19 patients appeared to have a more disrupted airway microbiome with frequent potential concurrent infections and a special trigger host immune response in certain pathways, such as interferon-gamma signaling. The immune-associated host transcriptional signatures of COVID-19 hold promise as a tool for improving COVID-19 diagnosis and indicating disease severity.

N-terminal truncation contributed to increasing thermal stability of mannanase Man1312 without activity loss.

BACKGROUND: The disordered residues on distal loops affect the molecular structural stability and on some occasions have regulatory roles in catalytic reaction. To increase understanding of the influence of distal residue mutation, this study explored the thermostability and enzymatic activity of mannanase Man1312 deletion mutants. The focus was on residues located on the N-terminal region because they are more disordered and changeable. The effects of N-terminal truncation on enzymatic activity and thermal dynamics were investigated by spectrophotometry, circular dichroism and differential scanning calorimetry assays. RESULTS: The deletion mutants on V3, N7 and Q11 showed a marked increase in stability, while the enzymatic activity was significantly improved when triplet deletion was carried out. Triplet deletion MandVNQ showed around double the stability of its corresponding single-site and double-site deletion mutants. The Tm value of MandVNP was about 8 °C higher than that of Man1312. MandVNP had improved characteristics of Topt by 10 °C, t1/2 by 10 min and catalytic activity by 11% in comparison with Man1312. Analysis of spectra and modeling showed that MandVNQ had increased helix and strand contents. CONCLUSION: N-terminal truncation had positive effects on the thermostability and activity of mannanase.

Discovery of a CB2 and 5-HT1A receptor dual agonist for the treatment of depression and anxiety.

Cannabinoid CB2R agonists have gained considerable attention as potential novel therapies for psychiatric disorders due to their non-psychoactive nature, in contrast to CB1R agonists. In this study, we employed molecular docking to design and synthesize 23 derivatives of cannabidiol (CBD) with the aim of discovering potent CB2R agonists rather than CB2R antagonists or inverse agonists. Structure-activity relationship (SAR) investigations highlighted the critical importance of the amide group at the C-3' site and the cycloalkyl group at the C-4' site for CB2R activation. Interestingly, three CBD derivatives, namely 2o, 6g, and 6h, exhibited substantial partial agonistic activity towards the CB2 receptor, in contrast to the inverse agonistic property of CBD. Among these, 2o acted as a CB2R and 5-HT1AR dual agonist, albeit with some undesired antagonist activity for CB1R. It demonstrated significant CB2R partial agonism while maintaining a level of 5-HT1AR agonistic and CB1R antagonistic activity similar to CBD. Pharmacokinetic experiments confirmed that 2o possesses favorable pharmacokinetic properties. Behavioral studies further revealed that 2o elicits significant antidepressant-like and anxiolytic-like effects while maintaining a good safety profile.

Cannabidiol exhibits anxiolytic-like effects and antipsychotic-like effects in mice models.

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD's interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 µM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD's anxiolytic-like effects. Additionally, CBD's effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD's anxiolytic-like and antipsychotic-like effects.

Comparison of expression systems for the extracellular production of mannanase Man23 originated from Bacillus subtilis B23.

BACKGROUND: Mannanase is an enzyme that can catalyze random hydrolysis of beta-1,4-mannosidic linkages in the main chain of mannans, glucomannans and galactomannans which are the key polymers in hemicellulose. It has been used in a number of different industrial applications including food, feed, pharmaceutical, pulp/paper industries, and second generation biofuel. To optimize the expression system of mannanase Man23 gene, two kinds of vectors and host bacteria were determined and compared. RESULTS: Recombinants pHY-p43-man23 and pBPS-man23 were constructed and transferred into Bacillus subtilis WB600 and Brevibacillus brevis respectively. For mannanase Man23 gene, recombinant pHY-p43-man23 expressed in Brevibacillus brevis had higher production and activity. Compared to the wild-type Bacillus subtilis B23, the production of recombinant pHY-p43-man23 in B. brevis increased by 10 times and activity increased by 21.3%. pHY-p43-man23 in B. brevis had activity at the range of 20 ~ 70 °C but its optimum temperature was 50 °C and had activity from pH 4 ~ 10 but its optimum pH was around 7. This demonstrated the recombinant had improved stability as well. CONCLUSIONS: Mannanase is an important industrial enzyme and combination of vector pHY-p43 and host Brevibacillus brevis is a novel expression system for a mannanase decoding gene. This work aims at exploring a better expression system of mannanase Man23 decoding gene for industrial application.

Mild acid hydrolysis on Fucan sulfate from Stichopus herrmanni: Structures, depolymerization mechanism and anticoagulant activity.

Fucan sulfate (FS) from sea cucumbers possesses linear sequences with repeating units that differ principally in the pattern of sulfation and position of glycosidic linkage. FS from Stichopus herrmanni (ShFS) was preliminarily identified as the relatively simple structure {-3)-L-Fuc2S-(α1-}n. Herein, mild acid hydrolysis was employed on ShFS to yield 21 oligosaccharides. Analyses on their structures complemented the features of ShFS to refine its spectral signal assignments. Combining with the methylation analysis, unit L-Fuc2S4S was determined as the micro-component in its intact structure. The irregularity came from minor sulfation on O-4. Temperature and acid concentration were the critical parameters to the depolymerization and formation of oligosaccharides. Meanwhile, a three-step cleavage of the hydrolysis mechanism involving the partial O-2 de-sulfation and preferential cleavage between Fuc0S and Fuc2S4S was proposed. Bioactivity assays revealed that the Mw 15-16 kDa conferred the potent anticoagulation via inhibiting the thrombin activity mediated by heparin cofactor II.

Gut Commensal Fungi Protect Against Acetaminophen-Induced Hepatotoxicity by Reducing Cyp2a5 Expression in Mice.

Background and Aims: Drug-induced liver injury (DILI) is a common cause of acute liver failure and represents a significant global public health problem. When discussing the gut-liver axis, although a great deal of research has focused on the role of gut microbiota in regulating the progression of DILI, the gut commensal fungal component has not yet been functionally identified. Methods: Mice were pretreated with fluconazole (FC) to deplete the gut commensal fungi and were then subject to acetaminophen (APAP) gavage. In addition, transcriptome sequencing was performed to identify differentially expressed genes (DEGs) between control and fluconazole-pretreated groups of the mice challenged with APAP. Results: Gut commensal fungi ablation through fluconazole pretreatment predisposed mice to APAP-induced hepatotoxicity, characterized by elevated serum liver enzyme levels and more severe centrilobular necrosis, which appears to be caused by robust inflammation and oxidative stress. The 16S rDNA sequencing results indicated that Akkermansia muciniphila abundance had significantly decreased in gut fungi-depleted mice, whereas increased abundance of Helicobacter rodentium was observed. The gene interaction network between DEGs identified by the transcriptome sequencing highlighted a significant enrichment of Cyp2a5 in the liver of APAP-treated mice that were preadministrated with fluconazole. Pharmacological inhibition of Cyp2a5 by 8-methoxypsoralen (8-MOP) could significantly attenuate hepatic inflammation and oxidative stress in mice, thereby conferring resistance to acute liver injury caused by APAP administration. Conclusion: Our data highlighted the significance of gut commensal fungi in hepatic inflammation and oxidative stress of APAP mice, shedding light on promising therapeutic strategies targeting Cyp2a5 for DILI treatment.

Fine-Scale Population Admixture Landscape of Tai-Kadai-Speaking Maonan in Southwest China Inferred From Genome-Wide SNP Data.

Guizhou Province harbors extensive ethnolinguistic and cultural diversity with Sino-Tibetan-, Hmong-Mien-, and Tai-Kadai-speaking populations. However, previous genetic analyses mainly focused on the genetic admixture history of the former two linguistic groups. The admixture history of Tai-Kadai-speaking populations in Guizhou needed to be characterized further. Thus, we genotyped genome-wide SNP data from 41 Tai-Kadai-speaking Maonan people and made a comprehensive population genetic analysis to explore their genetic origin and admixture history based on the pattern of the sharing alleles and haplotypes. We found a genetic affinity among geographically different Tai-Kadai-speaking populations, especially for Guizhou Maonan people and reference Maonan from Guangxi. Furthermore, formal tests based on the f 3 /f 4 -statistics further identified an adjacent connection between Maonan and geographically adjacent Hmong-Mien and Sino-Tibetan people, which was consistent with their historically documented shared material culture (Zhang et al., iScience, 2020, 23, 101032). Fitted qpAdm-based two-way admixture models with ancestral sources from northern and southern East Asians demonstrated that Maonan people were an admixed population with primary ancestry related to Guangxi historical people and a minor proportion of ancestry from Northeast Asians, consistent with their linguistically supported southern China origin. Here, we presented the landscape of genetic structure and diversity of Maonan people and a simple demographic model for their evolutionary process. Further whole-genome-sequence-based projects can be presented with more detailed information about the population history and adaptative history of the Guizhou Maonan people.

Personality Characteristics and Emotional Distress Among Chinese Pregnant Women: A Moderated Mediation Model.

Previous studies have suggested that certain personality characteristics are associated with emotional distress during pregnancy. However, the underlying mechanism of this association is rarely understood. The current study investigated the links between personality and pregnant women's emotional distress (depressive and anxiety symptoms), tested the chain mediating effects of two resilience factors-social support and positive coping, and explored whether socioeconomic status (SES) could moderate the effects (including direct and/or indirect effects) of personality on their emotional distress. Results of a relatively large sample of pregnant women in China (N = 1157) showed positive associations for psychoticism and neuroticism with depressive and anxiety symptoms as well as negative associations for extraversion with depression and anxiety. After controlling for four important variables (the first pregnancy or not, having adverse pregnancy experience or not, being pregnant as planned or not, and number of weeks of pregnancy), social support and positive coping acted as chain mediators on the associations of personality with depressive symptoms as well as of personality with anxiety. Overall, the association of personality and depressive symptoms demonstrated invariance across socioeconomic status (SES). However, SES moderated the relationship between personality and anxiety. Specifically, the negative association of positive coping with anxiety symptoms was weaker for low SES women than for high SES ones. Results highlight the importance of social support and positive coping to decrease personality-related depressive and anxiety symptom among pregnant women. Furthermore, identifying other resilience factors that alleviate anxiety in women with low SES is urgently called for.

A regular fucan sulfate from Stichopus herrmanni and its peroxide depolymerization: Structure and anticoagulant activity.

Marine sulfated polysaccharides have aroused widespread concern for their various structures and bioactivities. Peroxide depolymerization is a common strategy in analysis of structures and structure-activity relationships of polysaccharides. However, confirming the depolymerization process and exact structures of the degradation products is still a considerable challenge. This study reported the structures of a fucan sulfate (FS) from sea cucumber Stichopus herrmanni and its depolymerized products (dFS) prepared by peroxide degradation. The FS was elucidated with a highly regular structure, {-3)-L-Fuc2S-(α1-}n. Structure analysis of oligosaccharides purified from dFS suggested that peroxide degradation involved in cleavage of glycosidic bonds and oxidative modification of reducing end of sugar residue, while no break in sugar ring was observed. Both FS and series of dFSs exhibited significant anticoagulant activities due to their anti-thrombin effects in presence of heparin cofactor II and their potencies were related to their molecular sizes, dFS with ∼ 20 kDa showed the strongest activity.

Novel Cyclic Endomorphin Analogues with Multiple Modifications and Oligoarginine Vector Exhibit Potent Antinociception with Reduced Opioid-like Side Effects.

Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent µ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.

The spinal anti-allodynic effects of endomorphin analogs with C-terminal hydrazide modification in neuropathic pain model.

The present study was undertaken to further investigate the spinal anti-allodynic effects of endomorphins (EMs) and their C-terminal hydrazide modified analogs EM-1-NHNH2 and EM-2-NHNH2 in the spared nerve injury (SNI) model of neuropathic pain in mice. Our results demonstrated that intrathecal (i.t.) administration of endomorphin-1 (EM-1), endomorphin-2 (EM-2), EM-1-NHNH2 and EM-2-NHNH2 produced potent anti-allodynic effects ipsilaterally in neuropathic pain model. Judging from the area under the curve (AUC) values, these two analogs exhibited higher antinociception than their parent peptides. Moreover, they also displayed significant antinociceptive effects in the contralateral paw administered intrathecally. Interestingly, EM-1 and its analog EM-1-NHNH2 displayed their antinociception probably by µ2-opioid receptor subtype since the µ1-opioid receptor antagonist naloxonazine didn't significantly block the anti-allodynia of EM-1 and EM-1-NHNH2, which implied a same opioid mechanism. However, the anti-allodynia induced by EM-2, but not EM-2-NHNH2 was significantly reduced by both µ1-opioid antagonist, naloxonazine and κ-antagonist, nor-binaltorphamine (nor-BNI), indicating multiple opioid receptors were involved in the anti-allodynic effects of EM-2. Most importantly, EM-1-NHNH2 decreased the antinociceptive tolerance, and EM-2-NHNH2 displayed non-tolerance-forming antinociception. Therefore, C-terminal amide to hydrazide conversion changed the spinal antinociceptive profiles of EMs in neuropathic pain. The present investigation is of great value in the development of novel opioid therapeutics against neuropathic pain.

NMR characterization and anticoagulant activity of the oligosaccharides from the fucosylated glycosaminoglycan isolated from Holothuria coluber.

A glycosaminoglycan was isolated from the sea cucumber Holothuria coluber (HcFG). A series of oligosaccharide fragments (dp range 3-11) were prepared from its ß-eliminative depolymerized product (dHcFG). Extensive NMR characterization of the oligosaccharides indicated the d-GlcA-ß1,3-d-GalNAc4S6S repeating disaccharide backbone was substituted by monosaccharide branches comprising of Fuc2S4S, Fuc3S4S and Fuc4S, linked to O-3 of d-GlcA. For the prevailing Fuc3S4S at nonreducing end of dHcFG, the ß-eliminative depolymerization process of HcFG was compared with those of the FGs from Actinopyga miliaris (AmFG, branched with Fuc3S4S) and Stichopus variegatus (SvFG, branched with Fuc2S4S). The result suggested that d-GlcA substituted with Fuc3S4S was more susceptible to depolymerization than that with Fuc2S4S. It might be due to the larger steric hindrance effects from Fuc2S4S on the esterification of GlcA. Biological assays confirmed that the minimum chain length (dp8), regardless of the Fuc branch types, was required for the potent anti-iXase and anticoagulant activities in FG fragments.

A new fucosylated glycosaminoglycan containing disaccharide branches from Acaudina molpadioides: Unusual structure and anti-intrinsic tenase activity.

A fucosylated glycosaminoglycan (AmFG) was extracted from the sea cucumber Acaudina molpadioides. And a series of oligosaccharides were purified from the size-homogeneous fractions, which were prepared from the ß-eliminative depolymerized AmFG. According to "bottom-up" strategy, the precise structure of AmFG was elucidated by analyzing the structures of these purified oligosaccharides, combining with NMR analysis of its free-radical depolymerized product. It contained a CS-E-like backbone, and each GlcUA was branched with a mono- or di-sulfated fucose (Fuc) at O-3. Intriguingly, besides two types of monosaccharide branches, Fuc2S4S (60 %) and Fuc4S (25 %), that were common in FG, AmFG also contained an unusual disaccharide branch GalNAc-α1,2-Fuc3S4S (15 %); this is the first report of such a structure in a glycosaminoglycan. Biological assays indicated that native AmFG and its oligosaccharides had potent anticoagulant and intrinsic tenase (iXase) inhibitory activities in a chain length-dependent manner. For these oligosaccharides, octasaccharide was the minimum structural fragment for potent anti-iXase activity, and the disaccharide branch might enhance this activity.

Relationship between Helicobacter pylori infection and obesity in Chinese adults: A systematic review with meta-analysis.

BACKGROUND: Obesity is highly prevalent worldwide. More and more studies have been conducted on the relationship between H. pylori infection and obesity or overweight. But the relationship between them is controversial in the literatures and there is no comprehensive evidence for the correlation. AIM: To evaluate the prevalence of H. pylori infection in Chinese adult subjects who received routine physical examinations and the relationship between H. pylori and obesity. METHODS: Literatures on H. pylori infection and obesity in Chinese population were searched in online databases. Relevant data were extracted independently by two researchers and meta-analysis was performed by using Review manager 5.3 software. RESULTS: 22 articles were selected with a total sample size of 178033. The pooled prevalence of H. pylori was 42% (95%CI: 37% to 47%) and mean difference of BMI between subjects with and without H. pylori infection was 0.94 (95%CI: -0.04 to 1.91). 9 eligible studies with 27111 subjects were used to calculated pooled OR value because they contained obesity groups. The OR value showed that H. pylori-positive subjects tended to be obese at a risk of 1.20 (95% CI: 1.13 to 1.28). CONCLUSION: In China, obesity has association with H. pylori infection. H. pylori infection may be one of the risk factors for obesity.

The Effectiveness of Music Therapy for Terminally Ill Patients: A Meta-Analysis and Systematic Review.

CONTEXT: The quality of death has increasingly raised concern because of the physical and psychological suffering of patients with advanced disease. Music therapy has been widely used in palliative care; however, its physical and mental effectiveness remains unclear. OBJECTIVE: To assess the effectiveness of music therapy during palliative care in improving physiology and psychology outcomes. METHODS: Randomized controlled trials evaluating music therapy for terminally ill patients were searched and included from inception up to April 25, 2018. The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook V.5.1.0. RESULTS: In this study, 11 randomized controlled trials (inter-rater agreement, κ = 0.86) involving 969 participants were included. The quality of the included studies ranged from moderate to high. Compared with general palliative care, music therapy can reduce pain (standardized mean difference: -0.44, 95% confidence interval: -0.60 to -0.27, P < 0.00001) and improve the quality of life (standardized mean difference: 0.61, 95% confidence interval: 0.41 to 0.82, P < 0.00001) in terminally ill patients. In addition, anxiety, depression, and emotional function are improved as well. However, no significant differences were found in the patient's physical status, fatigue, and social function. CONCLUSION: This meta-analysis study demonstrated that music therapy served as an effective intervention to alleviate pain and psychological symptoms of terminally ill patients. However, considering the limitation of the quantity of the studies included, these results would need to be further confirmed.

Precise structures and anti-intrinsic tenase complex activity of three fucosylated glycosaminoglycans and their fragments.

Fucosylated glycosaminoglycan (FG), a glycosaminoglycan derivative containing distinct sulfated fucose (FucS) branches, displays potent anticoagulant activity by inhibiting the intrinsic tenase complex (iXase). Herein, AmFG, SvFG and HaFG from three species of sea cucumbers were isolated and depolymerized by ß-eliminative cleavage. Three series of fragments, A1-A4, S1-S4 and H1-H4, were purified from the depolymerized FGs. Based on structural analysis of these fragments, three FGs were deduced as -{→4)-[L-FucS-α(1→3)]-D-GlcA-ß(1→3)-D-GalNAc4S6S-ß(1}n-. The structures differed in sulfation types of FucS, namely, most of FucS in AmFG was Fuc3S4S, but the FucS in SvFG was Fuc2S4S, while the FucS in HaFG was Fuc3S4S, Fuc2S4S and Fuc4S. However, all FucS branches attached to C-3 of GlcA as monosaccharides. Anticoagulant and anti-iXase assays showed the octasaccharide is the minimum fragment for potent anticoagulant activity via anti-iXase irrespective of FucS types. Among FG fragments with same degree of polymerization, oligosaccharides containing Fuc2S4S had more potent anti-iXase activity.

An anticoagulant fucan sulfate with hexasaccharide repeating units from the sea cucumber Holothuria albiventer.

A fucan sulfate was isolated and purified from the sea cucumber Holothuria albiventer by papain enzymolysis, alkaline hydrolysis and ion-exchange chromatography. The water-soluble polysaccharide had high molecular weight and contained fucose and sulfate in a molar ratio of about 1:0.83. Methylation analysis of the native polysaccharide indicated that its glycosidic linkages and sulfate substituents might be at O-3 or O-3, 4 or O-2, 3, or O-2, 3, 4 positions. FT-IR and 2D NMR spectroscopies further revealed that the fucan sulfate is characteristically composed of a regular α (1 → 3) linked hexasaccharide repeating unit which is substituted with sulfate esters in a distinctive pattern. Anticoagulant properties of the fucan sulfate and its depolymerized product were assessed in vitro in comparison with a low-molecular-weight heparin. The fucan sulfate exhibits strong APTT and TT prolonging activities and intrinsic factor Xase inhibitory activity, and its molecular size seemed to be required for these activities.

Structural analysis and anticoagulant activities of two sulfated polysaccharides from the sea cucumber Holothuria coluber.

Sulfated polysaccharides such as fucosylated glycosaminoglycan and fucan sulfate from echinoderm possess complex chemical structure and various biological activities. The two sulfated polysaccharides were purified from the low-value sea cucumber Holothuria coluber. Their physicochemical properties and chemical structures were analyzed and characterized by chemical and instrumental methods. Structural analysis clarified that the sea cucumber fucosylated glycosaminoglycan contains a chondroitin sulfate-like backbone and fucosyl branches with four various sulfation patterns. The fucan sulfate with molecular weight of 64.6 kDa comprises a central core of regular α(1 → 4)-linked tetrasaccharide repeating units, each of which is linked by a 4-O-sulfated fucose residue. Anticoagulant assays indicated that these sulfated polysaccharides possessed strong APTT prolonging activities and intrinsic factor Xase inhibitory activities, both of which decreased with the reduction of their molecular weights. Our results expand knowledge on the structural types of sulfated polysaccharides from sea cucumbers and further illustrate their functionality.

Structural Elucidation and Biological Activity of a Highly Regular Fucosylated Glycosaminoglycan from the Edible Sea Cucumber Stichopus herrmanni.

Edible sea cucumbers are widely used as a health food and medicine. A fucosylated glycosaminoglycan (FG) was purified from the high-value sea cucumber Stichopus herrmanni. Its physicochemical properties and structure were analyzed and characterized by chemical and instrumental methods. Chemical analysis indicated that this FG with a molecular weight of ∼64 kDa is composed of N-acetyl-d-galactosamine, d-glucuronic acid (GlcA), and l-fucose. Structural analysis clarified that the FG contains the chondroitin sulfate E-like backbone, with mostly 2,4-di-O-sulfated (85%) and some 3,4-di-O-sulfated (10%) and 4-O-sulfated (5%) fucose side chains that link to the C3 position of GlcA. This FG is structurally highly regular and homogeneous, differing from the FGs of other sea cucumbers, for its sulfation patterns are simpler. Biological activity assays indicated that it is a strong anticoagulant, inhibiting thrombin and intrinsic factor Xase. Our results expand the knowledge on structural types of FG and illustrate its biological activity as a functional food material.