Emerging roles of plasmacytoid dendritic cell crosstalk in tumor immunity.

Plasmacytoid dendritic cells (pDCs) are a pioneer cell type that produces type I interferon (IFN-I) and promotes antiviral immune responses. However, they are tolerogenic and, when recruited to the tumor microenvironment (TME), play complex roles that have long been a research focus. The interactions between pDCs and other components of the TME, whether direct or indirect, can either promote or hinder tumor development; consequently, pDCs are an intriguing target for therapeutic intervention. This review provides a comprehensive overview of pDC crosstalk in the TME, including crosstalk with various cell types, biochemical factors, and microorganisms. An in-depth understanding of pDC crosstalk in TME should facilitate the development of novel pDC-based therapeutic methods.

Responses of biofilm communities in a hybrid moving bed biofilm reactor-membrane bioreactor system to sulfadiazine antibiotic exposure.

Antibiotics in wastewater can affect the structures and functions of bacterial communities, subsequently influencing how well a biological process performs. Therefore, the characteristics of bacterial community were investigated in a hybrid moving bed biofilm reactor-membrane bioreactor system when treating domestic wastewater containing sulfadiazine (SDZ). Results indicated total nitrogen removal reduced by 10.2%, 9.1%, 2.7% and 2.9%, respectively, with increasing carbon to nitrogen (C/N) ratios (2.5, 4, 6 and 9) when SDZ was present (0.5 mg/L). The microbial communities' analysis revealed that the abundance of nitrogen removal-related bacteria increased with C/N. Specifically, the abundance of ammonia-oxidizing bacteria (0.46%-0.90%) was low, and the nitrite-oxidizing bacteria (2.16%-7.13%) and denitrifying bacteria showed a significant increase (Hyphomicrobium: 0.57%-3.54%) when C/N ratio increased. The abundance of denitrifying bacterial declined by 4.82-8.56% at different C/N ratios, while nitrifying bacterial rose by 0.70-5.67%. Interestingly, the denitrifying bacteria Enterobacter, Sphingomonas and Gemmatimonas acted as mutualistic bacteria that stabilized denitrification.

The mechanism of formononetin/calycosin compound optimizing the effects of temozolomide on C6 malignant glioma based on metabolomics and network pharmacology.

The complex of formononetin and calycosin (FMN/CAL) shows a synergistic effect on temozolomide in the treatment of malignant glioma, however the mechanism is unclear. We investigated the mechanism through means of metabolomics, network pharmacology and molecular biology. FMN/CAL enhanced the inhibition of TMZ on the growth and infiltration of C6 glioma. The metabolomic results showed that the TMZ sensitization of FMN/CAL mainly involved 5 metabolic pathways and 4 metabolites in cells, 1 metabolic pathway and 2 metabolites in tumor tissues, and 7 metabolic pathways and 8 metabolites in serum. Further network pharmacological analysis revealed that NOS2 was a potential target for FMN/CAL to regulate the metabolism in TMZ-treated C6 glioma cells, serums and tissues, and TNF-α was another potential target identified in tissues. FMN/CAL down-regulated the expression of NOS2 in tumor cells and tissues, and reduced the secretion of TNF-α in tumor region. FMN/CAL promoted TMZ-induced C6 cell apoptosis by inhibiting NOS2, but the inhibition of cell vitality and migration was not through NOS2. Our work revealed that FMN/CAL can increase the sensitivity of malignant glioma to TMZ by inhibiting NOS2-dependent cell survival, which provides a basis for the application of this combination in adjuvant treatment of glioma.

Impact of light on anoxic/oxic reactors: performance, quorum sensing, and metagenomic characteristics.

The effect of light has raised attention on wastewater treatment. However, little research has concentrated on the influences of light on activated sludge. In this study, the influences of light on the performance, quorum sensing (QS) and metagenomic characteristics of anoxic/oxic reactors were investigated. The reactor without light (AO1) showed higher total nitrogen (TN) removal (79.15 ± 1.69%) than the reactor with light (AO2) (74.54 ± 1.30%), and significant differences were observed. It was observed that light facilitated the production of protein-like and tryptophan-like substances by employing parallel factor analysis for extracellular polymeric substance (EPS), resulting in more EPS production in AO2, indicating light was beneficial to EPS production. The concentrations of N-acyl-homoserine lactones (AHLs) were various in the two reactors, so the AHLs-mediated QS behaviors in both reactors were also different. These results revealed that light significantly influenced nitrogen removal, EPS, and QS. Metagenomic analysis based on Tax4Fun demonstrated that light reduced the denitrification, stimulated the polysaccharide and protein biosynthesis pathways and down-regulated the AHLs synthesis pathway, resulting in lower TN removal, more EPS production, and lower AHLs concentrations. Based on the above, the likely mechanism was proposed for the influences of light on the reactor.

Anti-tumor effects of Solanum nigrum L. extraction on C6 high-grade glioma.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum nigrum L. (SN) is a traditional Chinese medicine with anti-tumor effects, has been used in cancer for centuries, but the role on high-grade gliomas (HGG) is not clear. AIM OF THE STUDY: This work was to investigate the anti-tumor effects of SN extract on rat C6 glioma in vitro and in vivo, providing a new medium for the treatment of HGG. MATERIALS AND METHODS: After identification and quality inspection of SN medicinal materials by HPLC-MS/MS and HPLC, CCK8 and colony formation assay were conducted to study the effects of SN on vitality and proliferation of C6 cells. Cell morphology was evaluated by HE staining, and flow cytometry was used for apoptosis analysis. The effects on cell migration and invasion were determined by transwell and wound healing assay. Western blot was used to further investigate the influence of SN on migration, invasion and apoptosis of tumor cells. In addition, the rat intracranial transplanted tumor model was used to evaluate the effects of SN on growth and infiltration of tumor and proliferation of transplanted tumor cells. RESULTS: SN extract suppressed the viability of C6 cells in a dose-dependent manner. The extract attenuated cell cloning, migration and invasion, and induced cell Annexin V+ PI+ late-stage apoptosis. Besides, SN induced the expression of apoptotic proteins including Bax and Cleaved Caspase-3, downregulated anti-apoptotic protein Bcl-2, and decreased the level of migratory proteins MMP-2 and MMP-9. Moreover, SN reduced the growth and infiltration of C6 glioma tissue and suppressed the proliferation of tumor cells in rat brain. CONCLUSIONS: SN extract has significant inhibitory activity on the growth and invasion of C6 HGG in vivo and in vitro.

The antibacterial activity of Berberis heteropoda Schrenk and its effect on irritable bowel syndrome in rats.

The dried roots of Berberis heteropoda Schrenk have traditionally been used to treat acute gastroenteritis and dysentery. The aim of this study was to confirm the antibacterial activity of an extract of Berberis heteropoda Schrenk rootin vitro and its therapeutic effects on rats with diarrhea-predominant irritable bowel syndrome (D-IBS) in vivo, as well as to identify the related signaling pathways. A water extract of Berberis heteropoda Schrenk root (BHS) inhibited the growth of S. aureus, E. coli, P. aeruginosa and S. faecalis. BHS potentially damaged the structure of the bacterial cell membrane and decreased the activity of some membranous enzymes, eventually killing the S. aureus, E. coli, P. aeruginosa and S. faecalis bacteria. Oral administration of BHS (low, middle and high dose group, L, M and H) significantly alleviated the abdominal pain, diarrhea, and depression-like symptoms of D-IBS rats, and the efficacy index ranged from 30% to 60%, indicating that the BHS treatment was effective. BHS (L, M and H) alleviated the abnormal pathological changes in the brain, as evidenced by HE staining. The expression of CHAT, 5-HT, C-FOS and CGRP was reduced by the BHS treatment (L, M and H). Our findings provide novel insights into the use of the natural product BHS to inhibit pathogenic bacteria by destroying the bacterial structure, indicating that BHS possesses certain biological activities. Furthermore, BHS has the potential to alleviate diarrhea, abdominal pain and depression-like behaviors in D-IBS rats by regulating the brain-gut peptide levels.

Impact of the acetate/oleic acid ratio on the performance, quorum sensing, and microbial community of sequencing batch reactor system.

This study comprehensively investigated the impact of acetate/oleic acid ratios (80%/20%, 60%/40%, 40%/60%, and 20%/80%) on sequencing batch reactor (SBR) with respect to the variations in performance, quorum sensing (QS), and microbial community. Results showed that NH+4-N removal was not affected by the acetate/oleic acid ratios, while the COD, total nitrogen (TN), and PO3-4-P removal was considerably affected. The increasing oleic acid ratios led to severe sludge bulking, which was significantly positively correlated with proteins/polysaccharides (p < 0.001). The correlation of QS with the performance and sludge properties was also observed. High-throughput sequencing demonstrated that microbial compositions considerably shifted with varying acetate/oleic acid ratios. Moreover, the potential correlation of bacterial genera with the SBR performance and QS was proposed. This study elucidated the effect of acetate/oleic acid ratios on SBR from microbial viewpoint, which provided insights into fully understanding the essential roles of carbon source on wastewater treatment.

Insights into the effects of carbon source on sequencing batch reactors: Performance, quorum sensing and microbial community.

Effects of carbon source on the performance, quorum sensing (QS) and microbial communities in the sequencing batch reactors were investigated in this work. Among the chosen carbon source, sodium acetate (R1), glucose (R2), starch (R3) and Tween 80 (R4), sodium acetate was the best carbon source for nutrient removal, while starch was favorable for inducing the sludge bulking, and Tween 80 was beneficial to the production of extracellular polymeric substances (EPS) and proliferation of Microthrix parvicella. Additionally, the R2 value of linear correlation between sludge settleability and particle size in four reactors followed an order of R1 > R2 > R3 > R4. Moreover, Person correlation analysis showed that various significant correlations were observed in reactors fed with different carbon sources and the QS mainly mediated the production and component of EPS. High-throughput sequencing analysis revealed that the carbon source affected microbial communities and the Canonical correspondence analysis results indicated that QS related to microbial communities. It was inferred that the interactions between microbial communities and QS affected system performance.

Effect of water extract from Berberis heteropoda Schrenk roots on diarrhea-predominant irritable bowel syndrome by adjusting intestinal flora.

BACKGROUND: The aim of the present study was to investigate the antidiarrheal effect of Berberis heteropoda Schrenk roots (BHS), which are used by Chinese minorities to treat diarrhea, through regulation of intestinal flora and related signaling pathways. METHODS: Wistar rats were randomly divided into 6 groups: Control group (Con), Model group (Mod), three BHS groups (BHS-L (0.65 g/kg), BHS-M (1.955 g/kg), BHS-H (5.86 g/kg) and Bifidobacterium group (Bif). The model of diarrhea-based irritable bowel syndrome (D-IBS) was induced by intragastric administration combined with restraint stress. The CRD method was used to determine the AWR score and the Bristol fecal score. Quantification of the intestinal bacteria groups in feces was performed using colony counting on plates. The mRNA expression levels of Gpr41, Gpr43, TLR2, TLR4, and nuclear protein κB were determined by qRT-PCR, and the relative abundances of intestinal flora in the intestinal contents were determined by high-throughput gene sequencing ratios. RESULTS: Oral administration of BHS (L, M and H) significantly reduced the AWR score and the Bristol fecal score, significantly relieved diarrhea in D-IBS rats, reduced the number of Enterococci and Enterobacteria in feces, increased the number of Bifidobacteria and Lactobacilli, and upregulated the expression of SCFA in plasma. qRT-PCR analysis showed that the expression of TLR2, TLR4, Gpr41, Gpr43 and NF-κB in the BHS groups was downregulated. D-IBS rats reduced the abundance and diversity of intestinal flora and BHS (L, M and H) regulated the abundance and diversity of their intestinal flora. CONCLUSION: The above data suggest that BHS potentially alleviates diarrhea, intestinal flora disorder and intestinal inflammation in D-IBS rats by regulating the immunological pathways. BHS is a promising agent in the treatment of D-IBS.

Design Mechanism and Property of the Novel Fluorescent Probes for the Identification of Microthrix Parvicella In Situ.

In this study, two novel fluorescent probes, probe A and probe B were designed, synthesized and characterized, based on Microthrix parvicella (M. parvicella) preferring to utilize long-chain fatty acid (LCFA), for the labeling of M. parvicella in activated sludge. The molecular structure of probe A and probe B include long-chain alkane and LCFA, respectively. The results indicated that probe A and probe B had a large stokes shift of 118 nm and 120 nm and high quantum yield of 0.1043 and 0.1058, respectively, which were significantly helpful for the fluorescent labeling. As probe A was more stable than probe B in activated sludge, and the fluorescence intensity keep stable during 24 h, probe A was more suitable for labeling M. parvicella in situ. In addition, through the Image Pro Plus 6 (IPP 6) analysis, a quantitative relationship was established between sludge volume index (SVI) and integral optical density (IOD) of the labeled M. parvicella in activated sludge samples. The relationship between IOD and SVI conforms to Logistic curve (R² = 0.94).

Synthesis and characterization of the fluorescent probes for the labeling of Microthrix parvicella.

Although the fluorescent in situ hybridization (FISH) has been widely used to identify the Microthrix parvicella (M. parvicella), there are a few disadvantages and difficulties, such as complicated process, time consuming, etc. In this work, a series of fluorescent probes, which were modified by long-chain alkane with hydrophobic property and based on the property of M. parvicella utilizing long-chain fatty acids (LCFA), for the labeling of M. parvicella in bulking sludge were designed, synthesized, and characterized. The probes were characterized by ultraviolet-visible (UV-Vis) absorption spectra, fluorescence spectra, (1)H NMR spectra, and mass spectra, and the photostability and hydrophobic property of probes were investigated. All the results showed that the probes were quite stable and suitable for the fluorescent labeling. The probes had a large stoke shift of 98-137 nm, which was benefit for the fluorescent labeling. In the fluorescent labeling of M. parvicella by the synthesized probes, the probes had excellent labeling effects. By comparison of the images and the Image Pro Plus 6.0 analysis, the optimal concentration of the probes in the activated sludge sample for labeling was 0.010 mmol/L and the probe 3d had the best labeling. In addition, the effect of the duration time of probes was also investigated, and the results showed that the fluorescent intensity of probes hardly changed in a long period of time and it was suitable for labeling.

A Novel Separation Method of Microthrix parvicella Filaments from Activated Sludge by a Hydrophobic Plate.

The aim of this paper is to develop a novel method to separate Microthrix parvicella (M. parvicella) filaments from activated sludge easily and quickly, as there are a few difficulties in the isolation of M. parvicella filaments, such as complicated isolation process, time consuming, etc. In this work, a series of hydrophobic plate with and without microchannels have been prepared for the separation of M. parvicella filaments. The results showed that the presence of microchannels and hydrophobic property of the hydrophobic plates affected the separation efficiency of M. parvicella significantly. The scanning electron microscope and Keyence Digital Microscope analysis results showed that the diameter of microchannels was similar to the width of M. parvicella filament, which was beneficial for the fastening of M. parvicella filaments on the plate. The hydrophobic property of the prepared plates was tested by contact angle of water droplets, and the results displayed that the polydimethylsiloxane (PDMS) plate possessed the highest contact angle compared with that of other plates, like polymethylmethacrylate, polystyrene plate, and PDMS plate with no hydrophobic microchannels. Thus, it was concluded that the high separation efficiency of PDMS plates to M. parvicella filaments was due to its best hydrophobic property.