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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.

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-1β. 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-1β, 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.

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., Metabolism‐related gene pair signatures can predict the overall survival of patients with osteosarcoma and are related to tumor metastasis in patients with osteosarcoma.Patients in the MRGP low‐risk group may benefit from immunotherapy

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.

Chao Zhao,1,* Longqing Li,2,* Xiaoyue Guo,1 Dixiang Song,1 Minkai Wang,1 Yixuan Zhai,1 Fengdong Yang,1 Yake Xue,1 Xinting Wei1 1Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Henan, People’s Republic of China; 2Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinting WeiDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, No. 1 East Jianshe Road, District of Erqi, Henan, People’s Republic of ChinaTel +86-0371-13613860990Email weixinting777@126.comPurpose: Early identification of early mortality for glioblastoma (GBM) patients based on laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for isocitrate dehydrogenase (IDH) -wild-type (wt) GBM patients.Patients and Methods: We conducted a retrospective analysis of 194 IDH-wt GBM patients who underwent standard treatment. The probability of dying within 1 year after gross total resection (GTR) was defined as the end point “early mortality”. Retrospective collection of predictive factors including clinical characteristics and laboratory data at diagnosis.Results: Median follow-up time after GTR was 16 months (3– 41 months). Forty-two patients died within 1 year after surgery (1‐year mortality rate: 21.6%). All potential predictive factors were assessed on univariate analyses, which revealed the following factors as associated with higher risk of early death: older age (P = 0.013), occurrence of non-seizures symptoms (P = 0.042), special tumor positions (P = 0.046), higher neutrophil-to-lymphocyte ratio (NLR) (P = 0.015), higher red blood cell distribution width (RDW) (P = 0.019), higher lactate dehydrogenase (LDH) (P = 0.005), and higher fibrinogen (FIB) (P = 0.044). In a multivariate analysis, tumor location (P = 0.012), NLR (P = 0.032) and LDH (P = 0.002) were independent predictors of early mortality. The C-index of the nomogram was 0.795. The calibration curve showed good agreement between prediction by nomogram and actual observation.Conclusion: Tumor location, preoperative elevated NLR and serum LDH level were independent predictors for 1‐year mortality after GTR. We indicate that increased preoperative NLR or LDH may guide patients to review head magnetic resonance imaging (MRI) more frequently and regularly to monitor tumor progression.Keywords: glioblastoma, early mortality, risk factors, survival

PurposeIdentify immune-related lncRNA (IRL) signature related to the prognosis and immunotherapeutic efficiency for bladder cancer (BLCA) patients.MethodsA total of 397 samples, which contained RNA-seq and clinical information from The Cancer Genome Atlas (TCGA) database, were used for the following study. Then the Lasso penalized Cox proportional hazards regression model was used to construct prognostic signature. According to the optimal cut-off value determined by time-dependent ROC curve, low and high-risk groups were set up. One immunotherapy microarray dataset as validation set was used to verify the ability of predicting immunotherapy efficacy. Furthermore, more evaluation between two risk groups related clinical factors were conducted. Finally, external validation of IRL-signature was conducted in Zhengzhou cohort.ResultFour IRLs (HCP5, IPO5P1, LINC00942, and LINC01356) with significant prognostic value (PConclusionsThe novel IRL-signature has a significant prognostic value for BLCA patients might facilitate predicting the efficacy of immunotherapy.

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.

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.

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.

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.

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.

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 β-xylosidase, suggesting the existence of unknown enzymes or dual/multiple-specific enzymes for hydrolysis of the non-reducing end of xylan backbone.