Sea Buckthorn Flavonoid Extracted by High Hydrostatic Pressure Inhibited IgE-Stimulated Mast Cell Activation through the Mitogen-Activated Protein Kinase Signaling Pathway.

Sea buckthorn (Hippophaë rhamnoides L.), as one of the Elaeagnaceae family, has the significant function of anti-tumor, anti-inflammation, anti-oxidation, and other physiological activities. High hydrostatic pressure (HHP) extraction has the advantages of being easy and efficient, while maintaining biological activity. In this study, sea buckthorn flavonoid (SBF) was extracted with HHP and purified sea buckthorn flavonoid (PSBF) was isolated by AB-8 macroporous resin column. HPLC analysis was used to quantified them. In addition, the effect of anti-allergy in RBL-2H3 cells by SBF, PSBF, and their flavonoid compounds was evaluated. The results demonstrate the conditions for obtaining the maximum flavonoid amount of SBF: 415 MPa for 10 min, 72% ethanol concentration, and a liquid to solid ratio of 40 mL/g, which increased the purity from 1.46% to 13.26%. Both SBF and PSBF included rutin, quercitrin, quercetin, isorhamnetin, and kaempferol. In addition, quercitrin, kaempferol, and SBF could regulate Th1/Th2 cytokine balance. Moreover, extracellular Ca2+ influx was reduced by quercitrin and PSBF. Furthermore, rutin, quercetin, iso-rhamnetin, and SBF could also inhibit P-p38 and P-JNK expression, thereby suppressing the phosphorylation of the MAPK signaling pathways. Overall, SBF is effective for relieving food allergy and might be a promising anti-allergic therapeutic agent.

Gut microbiota composition influences outcomes of skeletal muscle nutritional intervention via blended protein supplementation in posttransplant patients with hematological malignancies.

BACKGROUND: Skeletal muscle atrophy is an important and independent predictor of survival after hematopoietic stem cell transplantation (HSCT). Our previous study found that soy-whey blended protein (SWP) can improve muscle mass in acute leukemia patients. OBJECTIVE: We aimed to explore potential factors that influence muscle outcomes after nutritional intervention. METHODS: In this case-control study, 13 patients who received HSCT and failed to improve muscle function within half a year were included. After two months of SWP intervention, the subjects were divided into two groups (MSI: muscle status improved; MNI: muscle status not improved). 16S rDNA sequencing, principal coordinate analysis (PCoA) and the PICRUSt algorithm were used to analyze the composition, structure and function of the intestinal microbiota between the groups. This study was registered in the Chinese Clinical Trial Registry (ChiCTR 1800017765). RESULTS: SWP significantly improved muscle status (muscle area: from 330.4 mm2 to 384.8 mm2, p = 0.02; muscle strength: from 19.2 kg to 21.3 kg, p = 0.04). However, there were a small number of subjects whose muscle status was not effectively improved. After SWP intervention, the diversity (Shannon: from 1.7 to 3.8, p = 0.01; Simpson: from 0.6 to 0.8, p = 0.015) of the intestinal microbiota in the MSI group increased significantly, whereas that in the MNI group did not. Principal component analysis (PCA) revealed separate groupings of the microbiota of the Baseline-MSI and Endpoint-MSI time points in the MSI group. Opposite patterns of microbial abundance change were found between the MSI group (75% of changed genera were increased) and the MNI group (80% of changed genera were decreased). Three bacterial taxa (negative correlation: Streptococcus; positive correlations: Ruminococcus and Veillonella) were significantly related to muscle improvement outcomes. Both pentose phosphate (p = 0.048) and amino acid biosynthesis (p = 0.039), which are related to muscle metabolism, were found to be significantly changed in the MSI group through PICRUSt algorithm prediction. CONCLUSIONS: Our results suggest that the intestinal microbiota plays important roles in the regulation of muscle metabolism.

The Effects of Fecal Donors with Different Feeding Patterns on Diarrhea in a Patient Undergoing Hematopoietic Stem Cell Transplantation.

Almost 90% of patients undergoing hematopoietic stem cell transplantation (HSCT) experience diarrheal episodes, which represent a severe, often life-threatening complication for these patients. Although fecal microbiota transplantation (FMT) represents an alternative treatment option for infection-related diarrhea, the application of FMT in HSCT patients is greatly restricted for safety reasons. Furthermore, the therapeutic outcomes of FMT as a diarrhea treatment are somewhat related to the choice of the FMT donor. Here, we comprehensively profiled the dynamic changes in the intestinal microbiota after FMT from two donors with different feeding patterns and the same severely diarrheal recipient undergoing HSCT via a 45-day clinical observation. Importantly, no adverse events attributed to FMT were observed. The stool volume and frequency of the patient were reduced when we used feces from donor #1 (mixed feeding), but these changes were not observed after FMT from donor #2 (exclusive breastfeeding). Interestingly, no obvious differences in overall diversity (Shannon) or richness (Chao1) between the two donors were observed. Additionally, Bifidobacterium accounted for 29.9% and 18.1% of OTUs in the stools of donors #1 and #2, respectively. Lactobacillus accounted for 16.3% and 2.9% of the stools of donors #1 and #2, respectively. Furthermore, through longitudinal monitoring of the patient, we identified 6 OTUs that were particularly sensitive to the different FMT complements. Together, we present a case report suggesting that the overall diversity of the intestinal microbiota may not be the only important element in the selection of an effective FMT donor.

Impact of body mass index at different transplantation stages on postoperative outcomes in patients with hematological malignancies: a meta-analysis.

Although the association between body mass index (BMI) and overall survival (OS) has been reported in leukemia patients of different ages, whether BMI levels at different stages of hematopoietic stem cell transplantation (HSCT) have different effects on postoperative survival remains controversial. We searched four electronic databases from inception through July 2017 without any language restrictions and included studies on different types of hematological malignancies reporting both BMI time points and HSCT. Of the 1420 articles identified, 26 articles were eligible for inclusion in this meta-analysis. Three weight groups (obese, overweight and underweight) were individually compared with the normal group. Summary risk estimates for OS and event-free survival (EFS) were calculated with random- or fixed-effects models. For BMI at the pre-HSCT stage, a statistically significant positive association of increased risk of OS (RR: 1.17; 95% CI: 1.08-1.27) and EFS (RR: 1.29; 95% CI: 1-1.67) was identified in underweight individuals compared with those with normal weights. For BMI in the HSCT stage, a lower BMI was significantly associated with poorer OS (RR: 1.34; 95% CI: 1.01-1.78) and EFS (RR: 1.53; 95% CI: 1.09-2.06) compared with a normal BMI. Our results indicated that lower BMI at the pre-HSCT stage or during HSCT is associated with poorer survival.

Genotyping of Enterocytozoon bieneusi and Subtyping of Blastocystis in Cancer Patients: Relationship to Diarrhea and Assessment of Zoonotic Transmission.

Enterocytozoon bieneusi (E. bieneusi) and Blastocystis are common pathogens responsible for diarrhea in humans, especially in immunocompromised individuals. The number of cancer patients has been increasing and diarrhea is a common clinical symptom in the treatment of cancers. To understand the prevalences and genotypes/subtypes of E. bieneusi and Blastocystis in cancer patients in China, to track the infection sources, and to explore the relationships between E. bieneusi and Blastocystis infections and diarrhea, 381 fecal specimens were collected from cancer patients. Each of them was analyzed for the presence of E. bieneusi and Blastocystis by PCR amplifying and sequencing the ITS region of the rRNA gene and the barcode region of the SSU rRNA gene, respectively. 1.3 and 7.1% of cancer patients were positive for E. bieneusi and Blastocystis, respectively. No statistical differences were observed in the infection rates between the groups by age, gender, and residence. E. bieneusi and Blastocystis were both significantly more common in cancer patients with diarrhea, and significant relationship of Blastocystis to diarrhea was found in chemotherapy group. Two E. bieneusi genotypes (D and a novel one named as HLJ-CP1) and two Blastocystis subtypes (ST1 and ST3) were identified with three novel ST1 sequences. This is the first report of occurrence and molecular characterizations of E. bieneusi and Blastocystis in cancer patients in China. E. bieneusi genotype D and Blastocystis ST1 and ST3 have been identified in humans and animals while one novel E. bieneusi genotype falling into zoonotic group 1, implying a potential of zoonotic transmission.

Protein blend ingestion before allogeneic stem cell transplantation improves protein-energy malnutrition in patients with leukemia.

Severe protein-energy malnutrition (PEM) and skeletal muscle wasting are commonly observed in patients with acute leukemia. Recently, the ingestion of a soy-whey protein blend has been shown to promote muscle protein synthesis (MPS). Thus, we tested the hypothesis that the ingestion of a soy-whey blended protein (BP) may improve the PEM status and muscle mass in acute leukemia patients. In total, 24 patients from the same treatment group were randomly assigned to the natural diet plus soy-whey blended protein (BP) group and the natural diet only (ND) group. Our data showed that protein and energy intake decreased significantly (P < .05) after transplantation in both groups. In the absence of the BP intervention, dramatic decreases in muscle-related indicators (i.e., anthropometric variables, muscle strength and serum protein) were observed in the majority (>50%) of the patients. However, 66% of the patients who ingested the BP before transplantation showed obvious increases in arm muscle area. The gripping power value (△post-pre or △post-baseline) was significantly higher in the BP group than in the ND group (P < .05). The ingestion of the BP also increased the levels of serum albumin, globulin and serum total protein to different extents. Notably, the average time to stem cell engraftment was significantly shorter for patients in the BP group (12.2 ± 2.0 days) than for patients in the ND group (15.1 ± 2.9 days). Collectively, our data supported that soy-whey protein can improve PEM status and muscle mass in leukemia patients.

Polarization of Monocytic Myeloid-Derived Suppressor Cells by Hepatitis B Surface Antigen Is Mediated via ERK/IL-6/STAT3 Signaling Feedback and Restrains the Activation of T Cells in Chronic Hepatitis B Virus Infection.

Chronic hepatitis B virus (HBV) infection is characterized by T cell tolerance to virus. Although inhibition of T cell responses by myeloid-derived suppressor cells (MDSCs) has been observed in patients with chronic hepatitis B (CHB), the mechanism for expansion of MDSCs remains ambiguous. In this study, a significant increased frequency of monocytic MDSCs (mMDSCs) was shown positively correlated to level of HBsAg in the patients with CHB. We further found hepatitis B surface Ag (HBsAg) efficiently promoted differentiation of mMDSCs in vitro, and monocytes in PBMCs performed as the progenitors. This required the activation of ERK/IL-6/STAT3 signaling feedback. Importantly, the mMDSCs polarized by HBsAg in vitro acquired the ability to suppress T cell activation. Additionally, treatment of all-trans retinoic acid, an MDSC-targeted drug, restored the proliferation and IFN-γ production by HBV-specific CD4(+) and CD8(+) T cells in PBMCs from patients with CHB and prevented increase of viral load in mouse model. In summary, HBsAg maintains HBV persistence and suppresses T cell responses by promoting differentiation of monocytes into mMDSCs. A therapy aimed at the abrogation of MDSCs may help to disrupt immune suppression in patients with CHB.

Oral administered particulate yeast-derived glucan promotes hepatitis B virus clearance in a hydrodynamic injection mouse model.

Hepatitis B virus (HBV) persistent infection is associated with ineffective immune response for the clearance of virus. Immunomodulators represent an important class of therapeutics, which potentially could be beneficial for the treatment of HBV infection. The particulate yeast-derived glucan (PYDG) has been shown to enhance the innate and adaptive immune responses. We therefore, assessed the efficacy of PYDG in enhancing HBV specific immune responses by employing the hydrodynamic injection-based (HDI) HBV transfection mouse model. Mice were intragatric administered PYDG daily for 9 weeks post pAAV/HBV1.2 hydrodynamic injection. PYDG treatment significantly promoted HBV DNA clearance and production of HBsAb compared to control mice. PYDG treatment resulted in recruitment of macrophages, dendritic cells (DCs) and effector T cells to the liver microenvironment, accompanied by a significantly augmented DCs maturation and HBV-specific IFN-γ and TNF-α production by T cell. In addition, enhanced production of Th1 cytokines in liver tissue interstitial fluid (TIF) was associated with PYDG administration. Live imaging showed the accumulation of PYDG in the mouse liver. Our results demonstrate that PYDG treatment significantly enhances HBV-specific Th1 immune responses, accompanied by clearance of HBV DNA, and therefore holds promise for further development of therapeutics against chronic hepatitis B.

HBsAg inhibits IFN-α production in plasmacytoid dendritic cells through TNF-α and IL-10 induction in monocytes.

Type I Interferon (IFN) is one of the first lines of defense against viral infection. Plasmacytoid dendritic cells (pDCs) are professional IFN-α-producing cells that play an important role in the antiviral immune response. Previous studies have reported that IFN-α production is impaired in chronic hepatitis B (CHB) patients. However, the mechanisms underlying the impairment in IFN-α production are not fully understood. Here, we report that plasma-derived hepatitis B surface antigen (HBsAg) and HBsAg expressed in CHO cells can significantly inhibit toll like receptor (TLR) 9-mediated Interferon-α (IFN-α) production in peripheral blood mononuclear cells (PBMCs) from healthy donors. Further analysis indicated that monocytes participate in the inhibitory effect of HBsAg on pDCs through the secretion of TNF-α and IL-10. Furthermore, TLR9 expression on pDCs was down-regulated by TNF-α, IL-10 and HBsAg treatment. This down-regulation may partially explain the inhibition of IFN-α production in pDCs. In conclusion, we determined that HBsAg inhibited the production of IFN-α by pDCs through the induction of monocytes that secreted TNF-α and IL-10 and through the down-regulation of TLR9 expression on pDCs. These data may aid in the development of effective antiviral treatments and lead to the immune control of the viral infections.