In vitro simulated digestion and fermentation characteristics of pectic polysaccharides from fresh passion fruit (Passiflora edulis f. flavicarpa L.) peel.

In this study, two pectic polysaccharides (PFP-T and PFP-UM) were extracted from fresh passion fruit peels using three-phase partitioning (TPP) and sequential ultrasound-microwave-assisted TPP methods, respectively, and their effects on the in vitro gastrointestinal digestion and fecal fermentation characteristics were examined. The results indicate that gastrointestinal digestion has a minimal effect on the physicochemical and structural characteristics of PFP-T and PFP-UM. However, during in vitro fecal fermentation, both undigested PFP-T and PFP-UM are significantly degraded and utilized by intestinal microorganisms, showing increased the total relative abundance of Firmicutes and Bacteroidota in the intestinal flora. Notably, compared with PFP-UM, PFP-T better promoted the reproduction of beneficial bacteria such as Prevotella, Megasphaera and Dialister, while suppressed the growth of harmful genera including Escherichia-Shigella, producing higher content of short-chain fatty acids. Therefore, our findings suggest that PFP-T derived from passion fruit peel has potential as a dietary supplement for promoting intestinal health.

Effects of direct addition of curdlan on the gelling characteristics of thermally induced soy protein isolate gels.

In this study, the effects of the direct addition of curdlan on the physicochemical, structural, and functional properties of heat-induced soy protein isolate (SPI) gels were evaluated. Results demonstrated that the direct incorporation of curdlan enhanced the gel-forming performance, water-holding capacity, and gel strength of heat-induced SPI gels. The presence of curdlan reduced the free water molecules and α-helix content in the SPI structure and contributed to the construction of stable SPI gels with uniform and compact network structures, as visually proven by microstructure observations. Moreover, compared with the SPI gel alone, the curdlan-SPI composite gels presented a more pronounced viscoelastic property and thermal stability mainly due to the intermolecular hydrogen bonding interaction between curdlan and the SPI molecules. Our findings suggest that the direct incorporation of curdlan can effectively ameliorate the gelling characteristics of heat-induced SPI gels, indicating its potential application as a promising gel improver in the food industry.

Polysaccharide extracted from cultivated Sanghuangporous vaninii spores using three-phase partitioning with enzyme/ultrasound pretreatment: Physicochemical characteristics and its biological activity in vitro.

Sanghuangporous vaninii, as a valuable dietary supplement and medicinal ingredient, contains abundant bioactive polysaccharides that have health-promoting effects. In the present study, four polysaccharides (SVSPs-C, SVSPs-E, SVSPs-U, and SVSPs-E/U) were extracted for the first time from S. vaninii spores by three-phase partitioning (TPP), enzyme pretreatment before TPP (E-TPP), ultrasonic pretreatment before TPP (U-TPP), and enzyme pretreatment followed by ultrasonic before TPP (E/U-TPP) methods, respectively. Their physicochemical characteristics and in vitro pharmacological functions were determined and compared. Results showed that four TPP-based extraction methods had remarkable impacts on the extraction yield, chemical properties, monosaccharide compositions, and molecular weights (Mw) of SVSPs. Specifically, SVSPs-E/U obtained by E/U-TPP showed the highest extraction yield (25.40 %), carbohydrate content (88.50 %), and the lowest protein content (0.86 %). The four SVSPs had high-Mw (183.8-329.1 kDa) and low-Mw (23.0-156.4 kDa) fractions and mainly consisted of galactose, glucose, and mannose with different contents. In vitro bioactivities assays indicated that SVSPs-E/U possessed stronger antioxidant, hypoglycemic, hypouricemic, immunostimulatory, and antitumor activities than those of SVSPs-C, SVSPs-E, and SVSPs-U. Therefore, our results provide an efficient and promising extraction technique for bioactive polysaccharides from S. vaninii spores, as well as SVSPs had the potential to be applied in functional food, pharmaceutical, and cosmetics fields.

Surgical Treatment of Osteosarcoma Induced Distant Pre-Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells.

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre-metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr-1+ myeloid cells are characterized to form a pre-metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage-associated molecular patterns released from surgical resection contribute to the formation of pre-metastatic niche in lung through IL-1ß secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre-metastatic niche in lung which is with important implications for developing rational therapies during peri-operative period.

The anti-hyperlipidemic effect and underlying mechanisms of barley (Hordeum vulgare L.) grass polysaccharides in mice induced by a high-fat diet.

Hyperlipidemia is a pathological disorder of lipid metabolism that can cause fatty liver, atherosclerosis, acute myocardial infarction, and other diseases, seriously endangering people's health. Polysaccharides have been shown to have lipid-lowering potential. In the current study, the anti-hyperlipidemia effect and potential mechanisms of a polysaccharide (BGP-Z31) obtained from barley grass harvested at the stem elongation stage in high-fat diet (HFD)-treated mice were investigated. Results showed that supplementation with BGP-Z31 (200 and 400 mg kg-1) not only suppressed obesity, organ enlargement, and fat accumulation caused by HFD, but also regulated dyslipidemia, relieved liver function injury, and ameliorated the oxidative stress level. Meanwhile, BGP-Z31 increased the concentrations of acetic acid, propionic acid, butyric acid, and isovaleric acid in HFD-induced mice. Gut microbiota analysis demonstrated that BGP-Z31 had no obvious effect on the gut microbiota diversity in mice treated with HFD, but it positively remodeled the intestinal flora structure by elevating the relative abundances of Bacteroides, Muribaculaceae, and Lachnospiraceae and lowering the Firmicutes/Bacteroides value and the relative abundance of Desulfovibrionaceae. Therefore, our data suggested that BGP-Z31 can be used as a promising nutritional supplement for dietary intervention in hyperlipidemia.

Human milk oligosaccharides and infant gut microbiota: Molecular structures, utilization strategies and immune function.

Human milk oligosaccharides (HMOs) are a unique class of non-digestible carbohydrates present in the mother milk, which play a key role in the development of infant gut microbiota, epithelial barrier and immune function. The deficiency of HMOs in the bovine milk-based infant formula has been widely recognized as a major culprit for the much higher incidence of immune disorders of formula-fed infants. This report was to give an up-to-date review on the structure characteristics of HMOs and the possible mechanisms, and strategies for their cellular uptake, and metabolism by the gut bacteria and the associated effects on the infant gut microbiome, and immune function. Most previous studies have been carried out in animals or in vitro model systems on the utilization strategies for HMOs in infant bacteria and their roles in infant microbiome, and gut immune function. A few HMO molecules have been synthesized artificially and applied in infant formulas.

Modification and enhanced anti-inflammatory activity by Bifidobacterial fermentation of an exopolysaccharide from a medicinal fungus Cs-HK1.

The exopolysaccharide (EPS) from the mycelial fermentation of a medicinal fungus Cordyceps sinensis Cs-HK1 had shown significant anti-inflammatory activity previously, and EPS-LM was a highly active fraction with a relatively low molecular weight (MW) isolated from the Cs-HK1 EPS. This study was to assess the effects of Bifidobacterial fermentation in anaerobic conditions on the molecular properties and anti-inflammatory activity of EPS-LM. In both Bifidobacterial cultures (B. breve and B. longum), EPS-LM was fractionally consumed as a carbon source, increasing the bacterial growth and acetic acid production. Analytical results from the fermentation digesta (supernatant) suggested that EPS-LM was partially degraded to lower molecular weight (MW) products with modified structures during the Bifidobacterial fermentation. More interestingly, the higher MW digesta fraction containing the partially degraded EPS-LM showed even stronger inhibiting activity than the original EPS-LM on the LPS-induced pro-inflammatory responses in THP-1 cell culture, including NF-κB activation, release of NO, TNF-α and IL-8. The study has shown that the fermentation by selected Bifidobacterial strains is effective to modify natural polysaccharides with enhanced bioactivities.

Identification of an IRGP Signature to Predict Prognosis and Immunotherapeutic Efficiency in Bladder Cancer.

BACKGROUND: Identify immune-related gene pairs (IRGPs) signature related to the prognosis and immunotherapeutic efficiency for bladder cancer (BLCA) patients. MATERIALS AND METHODS: One RNA-seq dataset (The Cancer Genome Atlas Program) and two microarray datasets (GSE13507 and GSE31684) were included in this study. We defined these cohorts as training set to construct IRGPs and one immunotherapy microarray dataset as validation set. Identifying BLCA subclasses based on IRGPs by consensus clustering. The Lasso penalized Cox proportional hazards regression model was used to construct prognostic signature and potential molecular mechanisms were analyzed. RESULTS: This signature can accurately predict the overall survival of BLCA patients and was verified in the immunotherapy validation set. IRGP-signatures can be used as independent prognostic risk factor in various clinical subgroups. Use the CIBERSORT algorithm to assess the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. According to the results of GSVA, GSEA, and CIBERSORT algorithm, we found that IRGP is strikingly positive correlated with tumor microenvironment (TME) stromal cells infiltration, indicating that the poor prognosis and immunotherapy might be caused partly by enrichment of stromal cells. Finally, the results from the TIDE analysis revealed that IRGP could efficiently predict the response of immunotherapy in BLCA. CONCLUSION: The novel IRGP signature has a significant prognostic value for BLCA patients might facilitate personalized for immunotherapy.

Signature based on metabolic-related gene pairs can predict overall survival of osteosarcoma patients.

BACKGROUND: Osteosarcoma is a tumour of malignant origin in children and adolescents. Recent progression indicates that it is necessary to develop new therapies to improve the patient's prognosis rather than strengthen anti-tumour chemotherapy. Researchers recently realised that cancer is a kind of disease with a metabolic disorder, and metabolic reprogramming is becoming a new cancer hallmark. Hence, our study's primary purpose is to explore the value of genes related to osteosarcoma metabolism. METHODS: From public databases, three osteosarcoma datasets with adequate clinical information were obtained. Besides, the IMvigor dataset through the 'IMvigor' package as a supplement was downloaded, the metabolic-related genes were identified, and these genes were used to construct the metabolic-related gene pairs (MRGP). Based on the prognosis-related MRGP, two molecular subtypes were identified. There are significant differences in the metabolic characteristics between the two molecular subtypes. Subsequently, the MRGP signature is constructed using the least absolute shrinkage and selection operator regression method. Finally, use SubMap analysis to evaluate the response of patients in the MRPG signature group to immunotherapy. RESULTS: The MRGP signature can reliably predict overall survival in patients with osteosarcoma. The MRGP signature is also associated with osteosarcoma patients' metastatic status and can be used for subsequent risk classification of metastatic patients. The immunotherapy is more likely to benefit the patients in the MRGP low-risk group. CONCLUSION: Metabolic-related gene pairs signature can assess the prognosis of patients with osteosarcoma.

Isolation and Assessment of a Highly-Active Anti-Inflammatory Exopolysaccharide from Mycelial Fermentation of a Medicinal Fungus Cs-HK1.

The purpose of this work was to fractionate the complex exopolysaccharide (EPS) from a medicinal fungus Ophiocordyceps sinensis Cs-HK1 based on the molecular weight (MW) range and to assess the in vitro anti-inflammatory activity of different EPS fractions in THP-1 cell culture. The lower MW fraction (EPS-LM-1) showed a much higher anti-inflammatory activity. EPS-LM-1 was identified as a heteropolysaccharide consisting of mannose, glucose, and galactose residues with an average MW of 360 kDa. EPS-LM-1 significantly inhibited the lipopolysaccharide-induced inflammatory responses with the effective concentrations for 50% inhibition below 5 µg/mL on a few major proinflammatory markers. With such a notable in vitro anti-inflammatory activity, EPS-LM-1 is a promising candidate for the development of a new anti-inflammation therapy.

A Hematological-Related Prognostic Scoring System for Patients With Newly Diagnosed Glioblastoma.

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor. Recent studies have shown that hematological biomarkers have become a powerful tool for predicting the prognosis of patients with cancer. However, most studies have only investigated the prognostic value of unilateral hematological markers. Therefore, we aimed to establish a comprehensive prognostic scoring system containing hematological markers to improve the prognostic prediction in patients with glioblastoma. PATIENTS AND METHODS: A total of 326 patients with glioblastoma were randomly divided into a training set and external validation set to develop and validate a hematological-related prognostic scoring system (HRPSS). The least absolute shrinkage and selection operator Cox proportional hazards regression analysis was used to determine the optimal covariates that constructed the scoring system. Furthermore, a quantitative survival-predicting nomogram was constructed based on the hematological risk score (HRS) derived from the HRPSS. The results of the nomogram were validated using bootstrap resampling and the external validation set. Finally, we further explored the relationship between the HRS and clinical prognostic factors. RESULTS: The optimal cutoff value for the HRS was 0.839. The patients were successfully classified into different prognostic groups based on their HRSs (P < 0.001). The areas under the curve (AUCs) of the HRS were 0.67, 0.73, and 0.78 at 0.5, 1, and 2 years, respectively. Additionally, the 0.5-, 1-y, and 2-y AUCs of the HRS were 0.51, 0.70, and 0.79, respectively, which validated the robust prognostic performance of the HRS in the external validation set. Based on both univariate and multivariate analyses, the HRS possessed a strong ability to predict overall survival in both the training set and validation set. The nomogram based on the HRS displayed good discrimination with a C-index of 0.81 and good calibration. In the validation cohort, a high C-index value of 0.82 could still be achieved. In all the data, the HRS showed specific correlations with age, first presenting symptoms, isocitrate dehydrogenase mutation status and tumor location, and successfully stratified them into different risk subgroups. CONCLUSIONS: The HRPSS is a powerful tool for accurate prognostic prediction in patients with newly diagnosed glioblastoma.

Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients.

The purpose of this study is to establish the prognosis of osteosarcoma patients based on the characteristics of immune-related gene pairs. We used the lasso Cox regression model to construct and verify the signature consisting of 14 immune-related gene pairs. This signature can accurately predict the overall survival of osteosarcoma patients and is an independent prognostic factor for osteosarcoma patients. For this we constructed a signature-based nomogram. The results of the nomogram show that our signature can bring clinical net benefits. We then assessed the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. The result of gene set enrichment analysis shows the strong relationship between signature and immune system. Finally, we evaluated the relationship between signature and immunotherapy efficiency using algorithms such as TIMI and SubMap to explore patients who might benefit from immunotherapy. In conclusion, our signature can predict the overall survival rate of osteosarcoma patients and provide potential guidance for exploring patients who may benefit from immunotherapy.

Mechanistic insights into the structure-dependant and strain-specific utilization of wheat arabinoxylan by Bifidobacterium longum.

Arabinoxylan (AX), an important dietary fiber from cereal grains, is mainly metabolised in the large intestine by gut bacteria, especially bifidobacteria. This study investigated the uptake and metabolism of wheat AX by a Bifidobacterium longum strain that could grow well with AX as the sole carbon source. The bacterial growth rate showed a significant correlation to the molecular weight (MW) of AX and its acid hydrolysates. Assessment of the key AX degrading enzymes suggested that the uptake and consumption of AX involved extracellular cleavage of xylan backbone and intracellular degradation of both the backbone and the arabinose substitution. The preference for native or partially hydrolysed AX with single substitutions and a sufficiently high MW suggested the structure-dependant uptake by the bacterial cells. Genetic analysis of B. longum showed the lack of ß-xylosidase, suggesting the existence of unknown enzymes or dual/multiple-specific enzymes for hydrolysis of the non-reducing end of xylan backbone.

A high-molecular weight exopolysaccharide from the Cs-HK1 fungus: Ultrasonic degradation, characterization and in vitro fecal fermentation.

This work was to examine the impact of power ultrasound (US) on the molecular properties of a high-molecular weight (MW) exopolysaccharide (EPS) from the Cs-HK1 medicinal fungus and the utilization, and prebiotic function of the US-treated EPS fractions in human fecal microflora in vitro. The US treatment caused notable reduction of intrinsic viscosity, average MW and aggregate size of EPS in water but no significant changes in the molecular structure. The US-treated EPS fractions were consumed more rapidly by the fecal microflora, resulting in a higher total level of short chain fatty acids. They also affected the relative abundance in the microflora more beneficially than the original EPS. The results suggest that power US is effective for modifying and improving the prebiotic properties of high-MW polysaccharides.

Meta-Analysis of Hematological Biomarkers as Reliable Indicators of Soft Tissue Sarcoma Prognosis.

Background: Several recent studies have reported the reliable prognostic effect of hematological biomarkers in various tumors. Yet, the prognostic value of these hematological markers in soft tissue sarcoma (STS) remains inconclusive. Thus, the aim of this meta-analysis was to check the effect of hematological markers on the prognosis of STS. Methods: We systematically searched for relevant papers published before October 2019 in the PubMed and EMBASE databases. Overall survival (OS) and disease-specific survival (DSS) were the primary outcome, whereas disease-free survival was the secondary outcome. A thorough study of hazard ratios (HR) and 95% of confidence intervals (CIs) was done for determining the prognostic significance. Results: We performed 23 studies that comprised of 4,480 patients with STS. The results revealed that higher neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and platelet-to-lymphocyte ratio (PLR) were associated with poor OS/DFS (HR = 2.08/1.72, for NLR; HR = 1.92/1.75, for CRP, and HR = 1.86/1.61, for PLR). In contrast, a low lymphocyte-to-monocyte ratio (LMR) was relate to worse OS/DFS (HR = 2.01/1.90, for LMR). Moreover, pooled analysis illustrated that elevated NLR and CRP represents poor DSS, with HRs of 1.46 and 2.06, respectively. In addition, combined analysis revealed that higher Glasgow prognostic score (GPS) was linked to an adverse OS/DSS (HR = 2.35/2.77). Conclusion: Our meta-analysis suggested that hematological markers (NLR, CRP, PLR, LMR, and GPS) are one of the important prognostic indicators for patients affected by high-grade STS and patients with the STS being located in the extremity.

Anti-inflammation activity of exopolysaccharides produced by a medicinal fungus Cordyceps sinensis Cs-HK1 in cell and animal models.

This study was to assess the anti-inflammatory potential of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. The EPS was isolated from the Cs-HK1 mycelial fermentation broth by ethanol precipitation and purified by deproteinization and dialysis. The EPS had a total sugar content of 74.8% and a maximum average molecular weight (MW) over 107 Da, and consisted mainly of glucose and mannose, and a small amount of galactose and ribose. In THP-1 and RAW264.7 cell cultures, EPS significantly inhibited lipopolysaccharide (LPS)-induced inflammatory responses of the cells including the release of NF-κB and several pro-inflammatory factors such as NO, TNF-α and IL-1ß. In the murine model of LPS-induced acute intestinal injury, the oral administration of EPS to the animals effectively suppressed the expression of major inflammatory cytokines TNF-α, IL-1ß, IL-10 and iNOS and alleviated the intestinal injury. The results suggest that the Cs-HK1 EPS has notable anti-inflammatory activity and can be a potential candidate for further development of new anti-septic therapeutics. To the best of our knowledge, this is the first report on the anti-inflammation of an EPS from C. sinensis fungal fermentation.

Effects of exopolysaccharide fractions with different molecular weights and compositions on fecal microflora during in vitro fermentation.

This study was to investigate the potential prebiotic function of exopolysaccharide (EPS) from a medicinal fungus and the relationship to the molecular properties by in vitro human fecal fermentation. The EPS from Cordyceps sinensis Cs-HK1 mycelial fermentation was processed into three fractions with different monosaccharide contents, a higher molecular weight (MW) and a lower MW attained by two-step ethanol precipitation, and an intermediate MW by ultrasound-degradation of EPS. All the EPS fractions were well utilized during 24-48 h of fecal fermentation, leading to significant increases in the short chain fatty acid (SCFA) production. The consumption rate and production level of SCFAs varied slightly with the different EPS fractions. The EPS also influenced the composition and diversity of the fecal microflora, increasing the relative abundance of Firmicutes but suppressing that of Proteobacteria, which may be a beneficial effect for human health. Overall the results have shown that the Cs-HK1 EPS has significant prebiotic activity which is dependent on its molecular properties.