Fuzhuan brick tea is characterized in unique “golden flower” of Aspergillus cristatus. However, little information is available for intra- and extra-cellular polysaccharides from A. cristatus (IPS ...and EPS, respectively). Therefore, simulated digestion and fermentation in vitro were carried out to investigate whether IPS and EPS could be broken down in digestive system. Furthermore, their interactions with gut microbiota were investigated. It was found that IPS and EPS were utilized by gut microbiota to metabolize into short-chain fatty acids (SCFAs). The contents of total acids (SCFAs and lactic acid) in IPS and EPS groups increased to 39.30 ± 0.66 and 45.18 ± 1.68 mmol/L, respectively. IPS and EPS could obviously modulate the composition of gut microbiota. Thereinto, IPS could maintain the growth of OTU26 and OTU69 (Prevotella) and increase the relative levels of OTU30, OTU31, OTU35 and OTU56 (Bacteroides), whereas, EPS could maintain the growth of OTU26 and OTU48 (Prevotella) and increase the relative levels of OTU35, OTU56 and OTU63 (Bacteroides). OTU26, OTU61 and OTU69 (Prevotella) showed significantly positive correlations with propionic acid, OTU48 (Prevotella) and OTU56 (Bacteroides) showed significantly positive correlations with acetic acid. Hence, IPS and EPS could regulate the composition of gut microbiota, thereby promote production of SCFAs.
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•IPS and EPS could be degraded and utilized by gut microbiota.•IPS and EPS could modulate the composition of gut microbiota.•IPS and EPS promoted the growth of Prevotella and Bacteroides.•Key OTUs showed significantly correlations with production of SCFAs.
•FBTPS-3 could be utilized and degraded by inflammatory bowel disease (IBD) gut microbiota.•FBTPS-3 modulated the composition and structure of IBD gut microbiota.•FBTPS-3 could reverse Bacteroides ...and Escherichia/Shigella in IBD gut microbiota.•The metabolites of FBTPS-3 by gut microbiota showed significantly anti-inflammatory activity.•FBTPS-3 was expected as novel prebiotics for treatment of IBD.
The purified fraction 3 of polysaccharides from Fuzhuan brick tea (FBTPS-3) could attenuate the colitis and modulate the gut microbiota. However, the relationship between anti-inflammatory effect of FBTPS-3 and the gut microbiota is still unknown. Thus, the anaerobic fermentation in vitro was used to investigate the potential mechanism. FBTPS-3 could be utilized and degraded by gut microbiota from inflammatory bowel disease (IBD) subjects. Furthermore, FBTPS-3 could modulate the composition and structure of IBD gut microbiota toward to that of healthy group. FBTPS-3 showed a superior modulated effect on IBD gut microbiota by increasing Bacteroides and decreasing Escherichia/Shigella. Furthermore, the fermentation solution rather than FBTPS-3 itself showed anti-inflammatory effects on lipopolysaccharide-treated RAW264.7 macrophages, which might be due to the metabolites such as short-chain fatty acids (SCFAs). Thus, FBTPS-3 can be expected as novel prebiotics for treatment of IBD via modulating gut microbiota, and promoting the production of SCFAs.
Kudingcha made from the leaves of Ilex kudingcha and chlorogenic acid have antiobesity and intestinal microbiota modulating effects. However, the effects of kudingcha dicaffeoylquinic acids (diCQAs) ...on obesity and intestinal microbiota are still poorly understood. In the present study, the effects of kudingcha diCQAs on adipose accumulation and intestinal microbiota were investigated in high-fat-diet-fed mice. As a result, kudingcha diCQAs decreased the liver and adipose tissue masses, concentrations of serum inflammatory factors, and hepatic expressions of lipid synthesis related genes and increased the expressions of genes involved in lipid degradation in the liver. Kudingcha diCQAs also exhibited considerable effects on intestinal microbiota. They increased the relative abundances of Bifidobacterium and Akkermansia and affected the function of the microbial community including bile acid biosynthesis. Kudingcha diCQAs had antiobesity potential, possibly acting through affecting intestinal microbiota. Furthermore, the effects of kudingcha diCQAs on fat accumulation and intestinal microbiota had a dose-dependent manner.
Increasing evidence shows that the gut microbiota contributes to the occurrence and development of colitis. Kudingcha (KDC), made from the leaves of Ilex kudingcha, could mitigate inflammation, ...however, little is known about the relationship between modulatory effect on gut microbiota by KDC and improvement of colitis. In this study, the attenuating effects of KDC extract (KDCE) on dextran sulfate sodium (DSS)-induced colitis and gut microbiota in C57BL/6 mice were investigated. It was found that the supplementation of KDCE could alleviate typical symptoms of IBD including weight loss, colon shortening, intestinal barrier damage, and decreases in the colitis disease activity index and pro-inflammatory cytokines. Moreover, KDCE supplementation could reverse the alteration of gut microbiota in the colitic mice by increasing the abundances of potential beneficial bacteria, e.g. Odoribacter, Prevotella and Helicobacter, and decreasing the abundances of potential harmful bacteria, e.g. Parabacteroides, Bacteroides, Turicibacter, Parasutterella and Lachnospiraceae. The levels of short-chain fatty acids in feces, cecum contents and serum were also regulated by KDCE. Furthermore, the correlation analysis suggested that KDCE could attenuate DSS-induced colitis which might be related to the alteration of gut microbiota. Therefore, the modulation of gut microbiota by KDCE might be a potential strategy for improving inflammation-driven diseases.
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•Kudingcha extract (KDCE) attenuated DSS induced colitis.•KDCE enhanced gut barrier integrity and decreased inflammatory cytokines.•KDCE increased short chain fatty acids and modulated the gut microbiota.•KDCE attenuated colitis may through regulating the 8 key gut bacteria.
Ion channel is a pore-forming membrane protein that allows ions to pass through the cell membrane, which is essential for the continuation of life. Analysis of ion channel characteristics at the ...single cell level will help to study the role of cellular heterogeneity in disease progression and cellular signaling processes. In this study, we fabricate a photocleavable and entropy-driven reaction based electrochemical biosensor for ultrasensitive detection of human ether-a-go-go related gene (hERG) potassium channel activity on HEK293 cell. We employed an antibody-DNA1 to conjugate the hERG channel in the cell membrane via antibody-antigen reaction. The release of the DNA1 by photocleavable reaction will trigger an amplification reaction by using the Exonuclease III (Exo III) to generate intermediate DNA. In addition, two hairpin DNA (DNA3 and DNA4) was employed for the signal amplification. We well designed a toehold on DNA3 for intermediate DNA hybridization to form double-strand DNA that opens the DNA3 hairpin. The free DNA3 exposed the relocked toehold domain to open the DNA4. After the entropy-driven toehold-mediated displacement amplification reaction by using intermediate DNA, DNA4 hybridized with DNA3 effectively, making the ferrocene labeled on the 5′-termini DNA4 close to the Au electrode surface to produce the electrochemical response. Then, the displaced intermediate DNA was released from the cell surface into solution for the next entropy-driven reaction. After two steps amplification reaction, one ion channel triggered thousands of DNA3/DNA4 duplex on the biosensor surface. By using this biosensor, electrochemical curve of hERG ion channels on a single cell was obtained.
•Ion channel is a pore-forming membrane protein that allows ions to pass through the cell membrane.•In the heart, the hERG plays a very critical role in the repolarization of cardiac action potential.•We employed molecular machines strategy for building an electrochemical biosensor for hERG assay.•The strategy also employed photocleavable linker molecule.•We obtained electrochemical curve of hERG ion channels on a single cell level.
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•Lectins were associated with biological evolution process in living organisms.•Siglec-5 as an important lectin was regarded as biomarker of scores of immune-related diseases.•MoS2@Au ...nanocomposites were served as electrochemiluminescence emitters for fabrication of a Siglec-5 aptasensor.•Exonuclease III-powered DNA walker engineering was employed in the signal amplification process.
Lectins are highly specific binding proteins for glycoproteins which widely exist in living organisms, playing a vital role in exploring the biological evolution process, such as cellular proliferation, differentiation, carcinogenesis and apoptosis. Therefore, the content monitoring of lectin becomes particularly significant and urgent in the bioanalytical application. In this work, we fabricated an aptasensor, majorly capitalizing the eminent affinity between sialic acid-binding immunoglobulin (Ig)-like lectin 5 (Siglec-5) and nucleic acids aptamer (K19), with nontoxic MoS2@Au nanocomposites as electrochemiluminescence (ECL) emitters based on exonuclease III (Exo III)-powered DNA walker for the bioassays of Siglec-5. The DNA track was constructed on the emitters’ surface, providing a reliable platform for the DNA walker’s autonomous move. In the assay, the primer DNA in the DNA duplex was replaced by Siglec-5 due to the aptamer interactions and repeatedly released to participate in the movement of the DNA walker, further triggering cascade signal amplification. Finally, our aptasensor indicates significant potential for assays of Siglec-5 with a detection limit of 8.9 pM.
Genipin-cross-linked caseinophosphopeptide (CPP)–chitosan (CS) nanoparticles (smaller than 300 nm) showed significantly improved stability and adjustable release profile in the gastrointestinal (GI) ...tract. Optimal purification of the nanoparticles was established by centrifugation to terminate the cross-linking reaction, which was further confirmed and characterized by FT-IR. Results from transmission electron microscopy (TEM), dynamic light scattering (DLS), and electrophoretic mobility (ζ-potential) measurements revealed that genipin cross-linking significantly prevented the bursting of the CPP–CS nanoparticles in simulated stomach acid and their precipitation under neutral intestinal environment. Pepsin showed little impact on the nanoparticle colloid stability; however, trypsin induced their aggregations. Genipin cross-linking slowed the burst release of (−)-epigallocatechin-3-gallate (EGCG) from the nanoparticles. The EGCG-loaded nanoparticles showed strong cytotoxicity against cancer cells; meanwhile, the net nanoparticles demonstrated high biocompatibility. The findings in the present work provide fundamental information for the rational design of biopolymer nanoparticles as an effective delivery systems for polyphenols.
Phthalocyanines (Pcs) are a kind of potential photosensitizers for fluorescence imaging and photodynamic therapy (PDT). However, the clinical application of Pcs is suffered from their poor ...solubility, high aggregation tendency and low tumor-specificity. To address these problems, two biotin moieties were linked to the axial positions of silicon(IV) phthalocyanine (SiPc) through hydrophilic polyethylene glycol (PEG) linkers to synthesize a new water-soluble and tumor-targeting photosensitizer (compound 1). The introduction of PEG linkers on SiPc markedly reduced the aggregation tendency of the conjugate. In vitro assays also proved that compound 1 could specifically accumulate in biotin receptor (BR) positive Hela cells through the BR-mediated internalization. Owing to the good characteristics of water-solubility and low aggregation, the bioactivity of compound 1 was examined in the xenograft tumor model. In vivo imaging and tissue distribution studies showed that compound 1 selectively accumulated in the tumor tissue, with tolerable signals found in other organs of the tumor-bearing mice. Furthermore, compound 1 could significantly depress tumor progression in vivo under irradiation. After 14 days of the treatment, the tumor volumes were even smaller than the beginning size. All these results reveal that compound 1 is a promising candidate, with low aggregation tendency, high tumor-specificity and water-solubility, for in vivo tumor diagnosis and PDT treatment.
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•A new biotin receptor-targeted silicon(IV) phthalocyanine conjugate was synthesized.•This new conjugate is highly soluble and cannot aggregate in aqueous medium.•The conjugate can selectively accumulate in biotin receptor positive cancer cells or tumor tissues.•This conjugate is a promising photosensitizer for in vivo tumor diagnosis and tumor-targeted photodynamic therapy.
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•18FLN as a small molecule PD-L1 tracer was synthesized for PET imaging.•The radiotracer 18FLN was fluoridated via 18F-19F isotope exchange.•18FLN targeted tumor site of PD-L1 ...transfected melanoma-bearing mice.
Programmed cell death protein-ligand 1 (PD-L1) is a crucial biomarker in immunotherapy and its expression level plays a key role in the guidance of anti-PD-L1 therapy. It had been reported that PD-L1 was quantified by noninvasive imaging with more developed radiotracers. In our study, a novel 18Ffluoride labeled small molecule inhibitor, 18FLN was designed for positron emission tomography (PET) imaging in both PD-L1 transfected (A375-hPD-L1) and non-transfected (A375) melanoma-bearing mice. LN showed the specificity (IC50 = 50.39 ± 2.65 nM) to PD-L1 confirmed by competitive combination and cell flow cytometry (FACS) analysis. The radiotracer 18FLN was obtained via 18F-19F isotope exchange from precursor LN. After radiosynthesis, 18FLN was achieved with a high radiochemical purity (RCP) above 95% and got a favorable molar activity of 36.34 ± 5.73 GBq/μmol. 18FLN displayed the moderate affinity (Kd = 65.27 ± 3.47 nM) to PD-L1 by specific binding assay. And it showed 1.3-fold higher uptake in A375-hPD-L1 cells than that in A375 cells. PET imaging revealed that 18FLN could enter into PD-L1 expressing tumor site and visualize the outline of tumor. And tumor uptake (1.96 ± 0.27 %ID/g) reached the maximum at 15 min in the positive group, showed 2.2-fold higher than the negative (0.89 ± 0.31 %ID/g) or the blocked (1.07 ± 0.26 %ID/g) groups. Meanwhile, biodistribution could slightly distinguish the positive from the negative. The results indicated 18FLN would become an efficient tool for evaluating PD-L1 expression with further optimization.
Fuzhuan brick tea (FBT) possesses various health-promoting functions. However, the available information regarding biological activity of polysaccharides from FBT (FBTPS) is still limited. In this ...work, the chemical property, cytotoxicity and antioxidant activity in vitro and in vivo of FBTPS were evaluated. It was found that FBTPSs were typical acidic heteropolysaccharides mainly composed of Man, Rha, GalA, Glc, Gal and Ara with little molar content of Rib and GlcA. FBTPS showed little toxicity to human hepatic epithelial (L-02) cell. FBTPS exhibited antioxidant activities, including limited scavenging activity on DPPH free radicals (ranged from 54.3 ± 1.9 to 67.8 ± 2.5%), noticeable scavenging activity on superoxide radicals (over 85%), superior scavenging activity on ABTS radicals (near 100%), and protective effect on H2O2-induced oxidative injury in rat pheochromocytoma line 12 (PC12) cell. Moreover, FBTPS showed significant amelioration of high-fat diet-induced oxidative injury in mice. The results suggest that FBTPS, as natural safe antioxidants, may have potential application in functional foods.
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