Coexistence of Candida albicans and Enterococcus faecalis increases biofilm virulence and periapical lesions in rats.

The present study utilized an in vitro dual-species biofilm model and an in vivo rat post-treatment endodontic disease (PTED) model to investigate whether co-infection of Candida albicans and Enterococcus faecalis would aggravate periapical lesions. The results showed that co-culturing yielded a thicker and denser biofilm more tolerant to detrimental stresses compared with the mono-species biofilm, such as a starvation-alkalinity environment, mechanical shear force and bactericidal chemicals. Consistently, co-inoculation of E. faecalis and C. albicans significantly increased the extent of in vivo periapical lesions compared with mono-species infection. Specifically, coexistence of both microorganisms increased osteoclastic bone resorption and suppressed osteoblastic bone formation. The synergistic effects also up-regulated inflammatory cytokines including TNF-α and IL-6. In summary, coexistence of C. albicans and E. faecalis increased periapical lesions by enhanced biofilm virulence.

Co-circulation of coxsackieviruses A-6, A-10, and A-16 causes hand, foot, and mouth disease in Guangzhou city, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018. METHODS: The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene. RESULTS: There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively. CONCLUSIONS: CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.

Two-Way Cruise Nanosatellite Promotes Metastasis Inhibition by Immunochemotherapy.

Currently, immunochemotherapy based on tumor-associated macrophages (TAMs) is mainly used for elimination of M2 macrophages. However, these methods cannot make full use of the positive immune-modulatory effects of macrophages. This study explores a two-way cruise strategy for combining immunotherapy based on TAM phenotype reversal with classical chemotherapy, the nanosatellites (DOX@HFn-PGZL@Res) are proposed to accurately deliver the chemotherapeutic agents and immune activators to their respective target cells. When the delivery system is recruited to tumor microenvironment, the nanosatellites are separated into DOX@HFn and Res@GZL nanoparticles, which can enter cancer cells and M2-TAMs, respectively. The data show that DOX@HFn-PGZL@Res successfully re-educate M2 to M1 macrophages, resulting in an activated immune response and inhibition of tumor invasion and metastasis. In general, this work describes a two-way homing nanoplatform for the integration of immunotherapy and chemotherapy, which provides a new idea for the "attack-defense" integrated treatment of tumor.

One-Step Preparation of Tough and Self-Healing Polyion Complex Hydrogels with Tunable Swelling Behaviors.

Polyion complex (PIC) hydrogels formed by charge attraction of opposite charged polymers have received unique research interest. Their conventional preparation method, with a large amount of residual salt after polymerization, requires a long-term dialysis treatment to remove the salt and toughen the gel. Here, a promising strategy for the one-step preparation of tough PIC hydrogels without dialysis after polymerization is provided. Bicarbonate and proton ions are selected as the counter ions of the cationic monomer and anionic polymers, respectively. By a CO2 -generating reaction between the counter ions, the residual salt is removed before polymerization, and thus, a PIC hydrogel with tough mechanical performance can be obtained instantly without dialysis. Due to the absence of dialysis, the tough hydrogel can be formed with a wide range of ratios for the oppositely charged polymer with distinct swelling behaviors from non-swelling to super-swelling. This tunable swelling behavior shows the possibility for shape-morphing systems from this one-step method.

Quercetin-containing self-assemble proliposome preparation and evaluation.

The purpose of this study was to develop a liquid self-assemble proliposome for quercetin oral delivery. This liquid proliposome was prepared by dissolving phospholipids, surfactants and drug in ethanol. There was only one step in the preparation process of this liquid self-assemble proliposome and no special devices were required. The mechanism about proliposome transformation was discussed. Quercetin proliposomes with different cremorphor RH40 concentrations (0%, 20%, 23%, 26%, 30%) were prepared. The particle size and polydispersity index decreased as cremorphor RH40 concentration increased. Meantime, the drug entrapped efficiency decreased slightly with an increase in cremorphor RH40 concentration. The in vitro drug release showed prolonged drug release in case of proliposome and the release of quercetin was slower when cremorphor RH40 concentration was higher. The absorption of quercetin and its in vivo bioavailability were significantly improved by proliposome, which was evidenced by the in situ intestinal absorption and pharmacokinetic study. Besides, the obtained quercetin proliposome was with good stability when stored at room temperature. In conclusion, quercetin liquid self-assemble proliposome was successfully prepared. It could transform into liposomal vesicle with satisfied particle size and polydispersity index instantly when cremorphor RH40 was added. Cremorphor RH40 concentration in the formulation should below 26% to get higher drug entrapped efficiency (>90%) and less irritation. The drug release was affected by the cremorphor RH40 concentration and the required drug release could be obtained by adjusting cremorphor RH40 content. The enhanced bioavailability showed liquid self-assemble proliposome could be a promising vehicle for the oral delivery of quercetin.

Transcriptome analysis of secondary cell wall development in Medicago truncatula.

BACKGROUND: Legumes are important to humans by providing food, feed and raw materials for industrial utilizations. Some legumes, such as alfalfa, are potential bioenergy crops due to their high biomass productivity. Global transcriptional profiling has been successfully used to identify genes and regulatory pathways in secondary cell wall thickening in Arabidopsis, but such transcriptome data is lacking in legumes. RESULTS: A systematic microarray assay and high through-put real time PCR analysis of secondary cell wall development were performed along stem maturation in Medicago truncatula. More than 11,000 genes were differentially expressed during stem maturation, and were categorized into 10 expression clusters. Among these, 279 transcription factor genes were correlated with lignin/cellulose biosynthesis, therefore representing putative regulators of secondary wall development. The b-ZIP, NAC, WRKY, C2H2 zinc finger (ZF), homeobox, and HSF gene families were over-represented. Gene co-expression network analysis was employed to identify transcription factors that may regulate the biosynthesis of lignin, cellulose and hemicellulose. As a complementary approach to microarray, real-time PCR analysis was used to characterize the expression of 1,045 transcription factors in the stem samples, and 64 of these were upregulated more than 5-fold during stem maturation. Reverse genetics characterization of a cellulose synthase gene in cluster 10 confirmed its function in xylem development. CONCLUSIONS: This study provides a useful transcriptome and expression resource for understanding cell wall development, which is pivotal to enhance biomass production in legumes.

Oral delivery of pectin-chitosan hydrogels entrapping macrophage-targeted curcumin-loaded liposomes for the treatment of ulcerative colitis.

The oral delivery of anti-inflammatory drugs has been a promising strategy for enhancing the clinical efficacy of ulcerative colitis (UC) treatment strategies. However, achieving site specific drug delivery to colon tissues and target cells is a challenging task for formulation scientists. In this study, macrophages-targeted liposome-loaded pectin-chitosan hydrogels were developed for UC treatment via oral administration. Folate-functionalized cholesterol was synthesized as lipid membrane materials for the liposomes containing curcumin (CUR). The incorporation of the liposomal CUR within pectin-chitosan hydrogels resulted in a matrix that exhibited considerable sensitivity to colonic enzymes during in vitro release. The targeted delivery of hybrids was able to effectively reach macrophages. They also showed enhanced capability to downregulate TNF-α, IL-6, and IL-1ß in the lipopolysaccharide-induced Raw 264.7 cells model. DSS-induced mice modelshowed improved anti-UC effects, including accelerated mucosal repair and decreased inflammation and modulate the immune balance in the intestinal tissue of mice with colitis, which may be attributable to increased drug accumulation in the colonic lumen and improved internalization to target cells. Therefore, the incorporation of folate-modified liposomes containing CUR and pectin-chitosan physical hydrogels could potentially serve as a favorable approach for treating UC through an oral colon-targeted drug delivery system.

Cross-kingdom interaction between Candida albicans and oral bacteria.

Candida albicans is a symbiotic fungus that commonly colonizes on oral mucosal surfaces and mainly affects immuno-compromised individuals. Polymicrobial interactions between C. albicans and oral microbes influence the cellular and biochemical composition of the biofilm, contributing to change clinically relevant outcomes of biofilm-related oral diseases, such as pathogenesis, virulence, and drug-resistance. Notably, the symbiotic relationships between C. albicans and oral bacteria have been well-documented in dental caries, oral mucositis, endodontic and periodontal diseases, implant-related infections, and oral cancer. C. albicans interacts with co-existing oral bacteria through physical attachment, extracellular signals, and metabolic cross-feeding. This review discusses the bacterial-fungal interactions between C. albicans and different oral bacteria, with a particular focus on the underlying mechanism and its relevance to the development and clinical management of oral diseases.

The crosstalk between macrophages and bone marrow mesenchymal stem cells in bone healing.

Bone injury plagues millions of patients worldwide every year, and it demands a heavy portion of expense from the public medical insurance system. At present, orthopedists think that autologous bone transplantation is the gold standard for treating large-scale bone defects. However, this method has significant limitations, which means that parts of patients cannot obtain a satisfactory prognosis. Therefore, a basic study on new therapeutic methods is urgently needed. The in-depth research on crosstalk between macrophages (Mϕs) and bone marrow mesenchymal stem cells (BMSCs) suggests that there is a close relationship between inflammation and regeneration. The in-depth understanding of the crosstalk between Mϕs and BMSCs is helpful to amplify the efficacy of stem cell-based treatment for bone injury. Only in the suitable inflammatory microenvironment can the damaged tissues containing stem cells obtain satisfactory healing outcomes. The excessive tissue inflammation and lack of stem cells make the transplantation of biomaterials necessary. We can expect that the crosstalk between Mϕs and BMSCs and biomaterials will become the mainstream to explore new methods for bone injury in the future. This review mainly summarizes the research on the crosstalk between Mϕs and BMSCs and also briefly describes the effects of biomaterials and aging on cell transplantation therapy.

A multiple environment-sensitive prodrug nanomicelle strategy based on chitosan graftomer for enhanced tumor therapy of gambogic acid.

A novel multiple environment-sensitive polymeric prodrug of gambogic acid (GA) based on chitosan graftomer was fabricated for cancer treatment. Folic acid-chitosan conjugates was complexed with thermosensitive amine terminated poly-N-isopropylacrylamide (NH2-PNIPAM) to develop FA-CSPN. Gambogic acid was conjugated with the graftomer via esterification to achieve high drug-loading capacity and controlled drug release. The resulting amphiphilic prodrug, O-(gambogic acid)-N-(folic acid)-N'-(NH2-PNIPAM) chitosan graftomer (GFCP), could self-assemble into micelles. As expected, the micelles were stable and biocompatible, featuring pH-, esterase- and temperature-dependent manner of drug release. Moreover, the anticancer effect studies of GFCP micelles were performed using a tumor-bearing mouse model and cellular assays (tumor cell uptake assay, cytotoxicity and tumor-sphere penetration). Collectively, GFCP micelles show both potential in vivo and in vitro in improving the anticancer effectiveness of GA owing to high loading capacity, targeted tumor accumulation, and multiple tumor microenvironmental responsiveness.

Preparation of Fe3O4@PMAA@Ni Microspheres towards the Efficient and Selective Enrichment of Histidine-Rich Proteins.

Magnetic material is considered to as a major concern material for the enrichment of histidine-rich proteins (His-proteins) via metal-ion affinity. In this work, magnetic polymer microspheres with core-shell structure (Fe3O4@PMAA@Ni) were successfully prepared via reflux-precipitation polymerization followed by in situ reduction and growth of Ni2+. The obtained Ni nanofoams with flower-like structure and uniform pore size (3.34 nm) provided numerous binding sites for His-proteins. The adsorption performance of Fe3O4@PMAA@Ni microspheres for His-proteins was estimated via selectively separating bovine hemoglobin (BHb) and bovine serum albumin (BSA) from a matrix composed of BHb, BSA, and lysozyme (LYZ). The results indicated that Fe3O4@PMAA@Ni microspheres could efficiently and selectively separate His-proteins from the matrix, with a maximum adsorption capacity of ∼2660 mg/g for BHb. Moreover, Fe3O4@PMAA@Ni microspheres exhibited good stability and recyclability for BHb separation over seven cycles. Therefore, this work reported a novel and facile strategy to prepare core-shell Fe3O4@PMAA@Ni microspheres, which was promising for practical applications of His-protein separation and purification in proteomics.

Probiotics ameliorate alveolar bone loss by regulating gut microbiota.

OBJECTIVES: Oestrogen deficiency is an aetiological factor of postmenopausal osteoporosis (PMO), which not only decreases bone density in vertebrae and long bone but also aggravates inflammatory alveolar bone loss. Recent evidence has suggested the critical role of gut microbiota in osteoimmunology and its influence on bone metabolisms. The present study aimed to evaluate the therapeutic effects of probiotics on alveolar bone loss under oestrogen-deficient condition. MATERIALS AND METHODS: Inflammatory alveolar bone loss was established in ovariectomized (OVX) rats, and rats were daily intragastrically administered with probiotics until sacrifice. Gut microbiota composition, intestinal permeability, systemic immune status and alveolar bone loss were assessed to reveal the underlying correlation between gut microbiota and bone metabolisms. RESULTS: We found administration of probiotics significantly prevented inflammatory alveolar bone resorption in OVX rats. By enriching butyrate-producing genera and enhancing gut butyrate production, probiotics improved intestinal barrier and decreased gut permeability in the OVX rats. Furthermore, the oestrogen deprivation-induced inflammatory responses were suppressed in probiotics-treated OVX rats, as reflected by reduced serum levels of inflammatory cytokines and a balanced distribution of CD4+ IL-17A+ Th17 cells and CD4+ CD25+ Foxp3+ Treg cells in the bone marrow. CONCLUSIONS: This study demonstrated that probiotics can effectively attenuate alveolar bone loss by modulating gut microbiota and further regulating osteoimmune response and thus represent a promising adjuvant in the treatment of alveolar bone loss under oestrogen deficiency.

Candida albicans promotes tooth decay by inducing oral microbial dysbiosis.

Candida albicans has been detected in root carious lesions. The current study aimed to explore the action of this fungal species on the microbial ecology and the pathogenesis of root caries. Here, by analyzing C. albicans in supragingival dental plaque collected from root carious lesions and sound root surfaces of root-caries subjects as well as caries-free individuals, we observed significantly increased colonization of C. albicans in root carious lesions. Further in vitro and animal studies showed that C. albicans colonization increased the cariogenicity of oral biofilm by altering its microbial ecology, leading to a polymicrobial biofilm with enhanced acidogenicity, and consequently exacerbated tooth demineralization and carious lesion severity. More importantly, we demonstrated that the cariogenicity-promoting activity of C. albicans was dependent on PHR2. Deletion of PHR2 restored microbial equilibrium and led to a less cariogenic biofilm as demonstrated by in vitro artificial caries model or in vivo root-caries rat model. Our data indicate the critical role of C. albicans infection in the occurrence of root caries. PHR2 is the major factor that determines the ecological impact and caries-promoting activity of C. albicans in a mixed microbial consortium.

Sucrose promotes caries progression by disrupting the microecological balance in oral biofilms: an in vitro study.

Sucrose has long been regarded as the most cariogenic carbohydrate. However, why sucrose causes severer dental caries than other sugars is largely unknown. Considering that caries is a polymicrobial infection resulting from dysbiosis of oral biofilms, we hypothesized that sucrose can introduce a microbiota imbalance favoring caries to a greater degree than other sugars. To test this hypothesis, an in vitro saliva-derived multispecies biofilm model was established, and by comparing caries lesions on enamel blocks cocultured with biofilms treated with sucrose, glucose and lactose, we confirmed that this model can reproduce the in vivo finding that sucrose has the strongest cariogenic potential. In parallel, compared to a control treatment, sucrose treatment led to significant changes within the microbial structure and assembly of oral microflora, while no significant difference was detected between the lactose/glucose treatment group and the control. Specifically, sucrose supplementation disrupted the homeostasis between acid-producing and alkali-producing bacteria. Consistent with microbial dysbiosis, we observed the most significant disequilibrium between acid and alkali metabolism in sucrose-treated biofilms. Taken together, our data indicate that the cariogenicity of sugars is closely related to their ability to regulate the oral microecology. These findings advance our understanding of caries etiology from an ecological perspective.

Low density lipoprotein mimic nanoparticles composed of amphipathic hybrid peptides and lipids for tumor-targeted delivery of paclitaxel.

BACKGROUND: Low density lipoprotein (LDL) has been regarded as a promising antitumor drug vehicle. However some problems, such as rare source, difficulty of large-scale production, and potential safety concerns, hinder its clinical application. PURPOSE: The objective of this study is to develop a biomimetic LDL nanocarrier by replacing the native apolipoprotein B-100 (apoB-100) with an artificial amphipathic peptide and demonstrate its antitumor efficacy. METHODS: The amphipathic hybrid peptide (termed as FPL) consisting of a lipid binding motif of apoB-100 (LBMapoB)-polyethylene glycol (PEG)-folic acid (FA) was synthesized and characterized by 1H NMR and circular dichroism. FPL decorated lipoprotein-mimic nanoparticles (termed as FPLM NPs) were prepared by a modified solvent emulsification method. Paclitaxel (PTX) was incorporated into NPs and its content was quantified by HPLC analysis. The morphology of NPs was observed by transmission electron microscopy (TEM), and the particle size and zeta potential of NPs were determined by dynamic light scattering (DLS). The colloidal stability of FPLM NPs was evaluated in PBS containing bovine serum albumin (BSA). In vitro release of PTX loaded FPLM NPs was evaluated using the dialysis method. Cellular uptake and cytotoxity assayswere evaluated on human cervical cancer cells (HeLa) and lung cancer cells (A549). Tumor inhibition in vivo was investigated in M109 tumor-bearing mice via tail vein injection of Taxol formulation and PTX loaded NPs. RESULTS: The composition of FPLM NPs, including cholesteryl oleate, glyceryl trioleate, cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and FPL peptides, was optimized to be 5:1:1:3:10 (w/w). FPLM NPs had a spherical shape with a mean diameter of 83 nm and a negative charge (-12 mV). FPLM NPs with optimum formulation had good colloidal stability in BSA solution.The release of PTX from FPLM NPs was slow and sustained. The uptake of FPLM NPs was higher in folate receptor (FR) overexpressing tumor cells (HeLa cells) than in FR deficient tumor cells (A549 cells). The intracellular distribution indicated that FPLM NPs had the lysosome escape capacity. The internalization mechanism of FPLM NPs was involved with clathrin- and caveolae-mediated endocytosis and FR played a positive role in the internalization of FPLM NPs. The CCK-8 assay demonstrated that FPLM NPs exhibited notably better anti-tumor effect than Taxol formulation in vitro. Moreover, PTX loaded FPLM NPs produced very marked anti-tumor efficiency in M109 tumor-bearing mice in vivo. CONCLUSION: FPLM NPs is a promising nanocarrier which can improve the therapeutic effect and reduce the side effects of antitumor drugs.

Integrated generation of induced pluripotent stem cells in a low-cost device.

Human induced pluripotent stem cells (iPSCs) have unlimited proliferation capability and potential to differentiate into all somatic cells. Their derivatives contain patients' genetic information and can model many diseases. Additionally, derivatives of patient-specific iPSCs induce minimal immune rejection in vivo. With this unique combination of properties, iPSCs open the avenue to personalized medicine including personalized drug screening, toxicity test, cell therapy and tissue engineering. However, the further advance of iPSC-based personalized medicine is currently limited by the difficulty to generate iPSCs for large populations and at affordable cost. We here report a low-cost device to address this challenge. The device allows the entire bioprocess for generating high quality and quantity of iPSCs for one patient to be done automatically within a closed conical tube without cell passaging. Additionally, iPSCs can be further differentiated into somatic cells in the device. Thus, the device also allows integrated iPSCs generation, expansion and differentiation to produce any somatic cell types. This device can be made in large quantities at low cost for manufacturing iPSCs (and their derivatives in necessary) for large populations at affordable cost. It will significantly advance the iPSCs-based personalized medicine.

The oral microbiome of early stage Parkinson's disease and its relationship with functional measures of motor and non-motor function.

Changes in the function and microbiome of the upper and lower gastrointestinal tract have been documented in Parkinson's disease (PD), although most studies have examined merely fecal microbiome profiles and patients with advanced disease states. In the present study we sought to identify sensitive and specific biomarkers of changes in the oral microbiome of early stage PD through shotgun metatranscriptomic profiling. We recruited 48 PD subjects and 36 age- and gender-matched healthy controls. Subjects completed detailed assessments of motor, cognitive, balance, autonomic and chemosensory (smell and taste) functions to determine their disease stage. We also obtained a saliva sample for profiling of microbial RNA and host mRNA using next generation sequencing. We found no differences in overall alpha and beta diversity between subject groups. However, changes in specific microbial taxa were observed, including primarily bacteria, but also yeast and phage. Nearly half of our findings were consistent with prior studies in the field obtained through profiling of fecal samples, with others representing highly novel candidates for detection of early stage PD. Testing of the diagnostic utility of the microbiome data revealed potentially robust performance with as few as 11 taxonomic features achieving a cross-validated area under the ROC curve of 0.90 and overall accuracy of 84.5%. Bioinformatic analysis of 167 different metabolic pathways supported shifts in a small set of distinct pathways involved in amino acid and energy metabolism among the organisms comprising the oral microbiome. In parallel with the microbial analysis, we also examined the evidence for changes in human salivary mRNAs in the same subjects. This revealed significant changes in a set of 9 host mRNAs, several of which mapped to various brain functions and showed correlations with some of the significantly changed microbial taxa. Unexpectedly, we also observed robust correlations between many of the microbiota and functional measures, including those reflecting cognition, balance, and disease duration. These results suggest that the oral microbiome may represent a highly-accessible and informative microenvironment that offers new insights in the pathophysiology of early stage PD.

Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide.

The main purpose of present study was to develop novel chitosan-modified polylactic-co-glycolicacid nanoparticles (CS@PLGA NPs) for improving the bio-availability of tolbutamide (TOL). The TOL-loaded CS@PLGA NPs (TOL-CS@PLGA NPs) were fabricated with the solvent evaporation method. The cargo-free CS@PLGA NPs showed a diameter of 228.3±2.5nm monitored with a laser light particlesizer, and the transmission electron microscope (TEM) photographs revealed their "core-shell" structures. The Zeta potential of the original PLGA NPs and the cargo-free CS@PLGA NPs was measured to be -20.2±3.21mV and 24.2±1.1mV, respectively. The changes in Zeta potential indicated the CS chains were coated on the surfaces of the original PLGA NPs. The thermal gravity analysis (TGA) curves suggested that the CS chains improved the thermostability of the original PLGA NPs. The results of cells viability indicated the cargo-free CS@PLGA NPs were nontoxicity. The in vitro release profiles suggested that TOL-CS@PLGA NPs could release TOL in pH 7.4 phosphate buffer solution (PBS) at a sustained manner. Streptozotocin (STZ) was employed to build the diabetic rat models. The physiological changes in the islet ß cells confirmed the obtaining of diabetic rats. After treatment by gavage, the TOL-CS@PLGA NPs showed an excellent hypoglycemic effect. Therefore, the TOL-CS@PLGA NPs had a potential application in oral delivery of TOL.

The ratiometric fluorescence nanoparticle based on SiRB for pH detection of tumor.

Tumor pH detection and pH value change monitoring have been of great interest in the field of nanomedicine. In this study, a pH-sensitive near-infrared fluorescence probe SiRB (Si-rhodamine and Boronic acid group) was synthesized by introducing a boronic acid group into the silicon rhodamine structure. ICG (Indocyanine green) as the fluorescence internal standard and SiRB were loaded into PLGA (poly lactic-co-glycolic acid) to form PLGA-SiRB-ICG nanoparticle. The experiments showed that the size of the nanoparticle was about 90 nm, which can reach tumor passively by enhancing permeability and retention effect. PLGA in the acidic environment will accelerate the release of cleavage, and the fluorescence ratio of the two probes can reflect the specific pH value in the tumor. The results indicated that the nanoparticle could quantitatively measure the pH value of the tumor site, which is expected to be used in tumor research and treatment.

Scalable and physiologically relevant microenvironments for human pluripotent stem cell expansion and differentiation.

Human pluripotent stem cells (hPSCs) are required in large numbers for various biomedical applications. However, the scalable and cost-effective culturing of high quality hPSCs and their derivatives remains very challenging. Here, we report a novel and physiologically relevant 3D culture system (called the AlgTube cell culture system) for hPSC expansion and differentiation. With this system, cells are processed into and cultured in microscale alginate hydrogel tubes that are suspended in the cell culture medium in a culture vessel. The hydrogel tubes protect cells from hydrodynamic stresses in the culture vessel and limit the cell mass smaller than 400 µm in diameter to ensure efficient mass transport, creating cell-friendly microenvironments for growing cells. This system is simple, scalable, highly efficient, defined and compatible with the current good manufacturing practices. Under optimized culture conditions, the AlgTubes enabled long-term culture of hPSCs (>10 passages, >50 days) with high cell viability, high growth rate (1000-fold expansion over 10 days per passage), high purity (>95% Oct4+) and high yield (5.0 × 108 cells ml-1), all of which offer considerable advantages compared to current approaches. Moreover, the AlgTubes enabled directed differentiation of hPSCs into various tissue cells. This system can be readily scaled to support research from basic biological study to clinical development and the future industry-scale production.