Evaluation of post-dilatation on longitudinal stent deformation and postprocedural stent malapposition in the left main artery by optical coherence tomography (OCT): an in vitro study.

BACKGROUND: The diameter of the ostial and proximal left main coronary artery can be greater than 5.0 mm. However, the diameters of the mostly available coronary drug-eluting stents (DESs) are ≤ 4.0 mm. Whether high-pressure dilatation can increase the diameter of stents from 4.0 to 5.0 mm and whether post-dilatation leads to longitudinal stent deformation (LSD) of 4.0-mm-diameter stents have rarely been studied. Therefore, this study aims to evaluate LSD and stent malapposition of six types of commercially available 4.0-mm-diameter stents in China in a 5.0-mm-diameter artificial blood vessel model by optical coherence tomography (OCT) in vitro. METHODS: The left main coronary artery was simulated by a truncated cone-shaped silicone tube. The internal diameters were 4.0 mm at one end of the silicone tube and 5.0 mm at the other end. Six different types of coronary stents widely used in China were selected for this study. Each stent was respectively implanted into the simulated blood vessel and dilated to a diameter of 4.2 mm according to the stent-balloon pressure compliance table. The stents were subjected to post-dilatation with a 5.0 × 15-mm noncompliant balloon. The LSD ratio of the longitudinal axis of each stent and stent malapposition were measured through OCT, and any fractures of the stents were determined. RESULTS: None of the six types of stents fractured following post-dilatation. The longitudinal axes of the BuMA and Excrossal stents were slightly shortened, while the other stents were elongated after high-pressure post-dilatation. All stents expanded to a diameter of 5.0 mm without incomplete stent apposition, except for the Nano Plus stent, which remained malapposed after high-pressure post-dilatation. CONCLUSION: All 4.0-mm-diameter stents can be expanded to a diameter of 5.0 mm by noncompliant balloon post-dilatation without stent strut fracture. Most stents were found to be well apposed after high-pressure post-dilatation. However, LSD was observed after post-balloon dilatation. Stent malapposition might be positively correlated with the percentage change in stent length.

Mechanism insights into the histopathological changes of polypropylene microplastics induced gut and liver in zebrafish.

Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 µm across varying concentrations (300 mg/L and 600 mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.

Intracellular mRNA phase separation induced by cationic polymers for tumor immunotherapy.

The formation of biomolecular condensates via liquid‒liquid phase separation (LLPS) is an advantageous strategy for cells to organize their subcellular compartments for diverse functions. Recent findings suggest that RNA or RNA-related LLPS techniques have potential for the development of new cellular regulation strategies. However, manipulating RNA LLPS in living cells has great challenges. Herein, we report that cationic polymers (CPs) have strong RNA LLPS-inducing activity. By introducing CPs into living cells or RNA solutions, significant RNA LLPS was verified through confocal imaging, turbidity assays, and fluorescence recovery after photobleaching (FRAP) tests. Among them, turbidity kinetics determinations indicated that the hydrophilic positively charged amino groups on the CPs play essential roles in RNA phase separation. Moreover, the LLPS induced by the cationic polymers dramatically changed the gene expression patterns in the cells. Interestingly, we found that TGFß1 mRNA was highly encapsulated in the RNA droplets, which lowered the immunosuppressive capability of the tumor cells and triggered marked antitumor reactions in a mouse breast cancer model. Thus, we present here the CP-based modulation of RNA LLPS as a novel transcriptional manipulation method with potential for cancer immunotherapy drug development.

Identifying the Best Questions for Rapid Screening of Secondhand Smoke Exposure Among Children.

INTRODUCTION: Many children suffer from secondhand smoke exposure (SHSe), which leads to a variety of negative health consequences. However, there is no consensus on how clinicians can best query parents for possible SHSe among children. We employed a data-driven approach to create an efficient screening tool for clinicians to quickly and correctly identify children at risk for SHSe. METHODS: Survey data from mothers and biospecimens from children were ascertained from the Neurodevelopment and Improving Children's Health following Environmental Tobacco Smoke Exposure (NICHES) study. Included were mothers and their children whose saliva were assayed for cotinine (n = 351 pairs, mean child age = 5.6 years). Elastic net regression predicting SHSe, as indicated from cotinine concentration, was conducted on available smoking-related questions and cross-validated with 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to select the most predictive items of SHSe among children (n = 1670, mean child age = 8.4 years). RESULTS: Answering positively to at least one of the two final items ("During the past 30 days, did you smoke cigarettes at all?" and "Has anyone, including yourself, smoked tobacco in your home in the past 7 days?") showed area under the curve = .82, and good specificity (.88) and sensitivity (.74). These results were validated with similar items in the nationally representative NHANES sample, area under the curve = .82, specificity = .78, and sensitivity = .77. CONCLUSIONS: Our data-driven approach identified and validated two items that may be useful as a screening tool for a speedy and accurate assessment of SHSe among children. IMPLICATIONS: The current study used a rigorous data-driven approach to identify questions that could reliably predict SHSe among children. Using saliva cotinine concentration levels as a gold standard for determining SHSe, our analysis employing elastic net regression identified two questions that served as good classifier for distinguishing children who might be at risk for SHSe. The two items that we validated in the current study can be readily used by clinicians, such as pediatricians, as part of screening procedures to quickly identify whether children might be at risk for SHSe.

Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions.

Kaempferol (KAE) is a naturally occurring flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability, and suboptimal bioavailability greatly restrict its clinical application in cancer therapy. To address the aforementioned limitations and augment the antitumor efficacy of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizing agent, screened the optimal preparation process, and conducted a comprehensive investigation of their fundamental properties as well as the antitumor effects in the study. The findings indicated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was prominently improved compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable and had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, along with increased intracellular ROS production and higher apoptosis rates compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps had a longer duration of action in mice, significantly improved bioavailability, and showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity in 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared notably improved the defect and the antitumor effects of KAE, making it a promising nanodrug delivery system for KAE with potential applications as a clinical antitumor drug.

Destructing biofilms by cationic dextran through phase transition.

Eliminating biofilms from infected tissue presents one of the most challenging issues in clinical treatment of chronic wounds. In biofilms, the extracellular polymeric substances (EPS) form gel structures by electrostatic forces between macromolecules. We hypothesized that cationic polymers could induce the gel-to-sol phase transition of the network, leading to biofilms disruptions. We first validated this assumption by using polyethyleneimine (PEI) as a model molecule, and further synthesized two cationic dextrans with high biodegradability for in vitro and in vivo evaluation. All the cationic polymers could destruct Pseudomonas aeruginosa (P. aeruginosa) biofilms. Treating biofilm with cationic dextrans significantly enhanced the bacterial antibiotic sensitivity. When tested in a biofilm-presenting mouse wound healing model, the cationic dextrans efficiently controlled infection, and accelerated the healing process. Our findings suggest that devising cationic polymers to trigger phase transition of biofilm is an effective, straightforward, and perhaps generic strategy for anti-bacterial therapies.

Localized delivery of antisense oligonucleotides by cationic hydrogel suppresses TNF-α expression and endotoxin-induced osteolysis.

PURPOSE: To investigate the possibility of using localized nucleic drug delivery methods for the treatment of osteolysis-related bone disease. METHODS: A bio-degradable cationic hydrogel composed of gelatin and chitosan was used to deliver an antisense oligonucleotide (ASO) targeting murine TNF-α for the treatment of endotoxin-induced osteolysis. RESULTS: ASO combined with this hydrogel was released when it was digested by adhering cells. The released ASO was efficiently delivered into contacted cells and tissues in vitro and in vivo. When tested in animal models of edotoxin-induced bone resorption, ASO delivered by such means effectively suppressed the expression of TNF-α and subsequently the osteoclastogenesis in vivo. Osteolysis in the edotoxin-induced bone resorption animal models was blocked by the treatment. CONCLUSION: This is a successful attempt to apply localized gene delivery method to treat inflammatory diseases in vivo.

Transformation and kinetics of chlorine-containing products during pyrolysis of plastic wastes.

Pyrolysis can not only effectively dispose of plastic wastes but also reclaim valuable chemicals and biochar. However, the production and release of second pollutants, particularly chlorine-containing products, have been neglected. The mechanism for the transformation of chlorine during the pyrolysis of plastic wastes remains unclear. Herein, a thermogravimetric Fourier transform infrared mass spectrometry technology was used to investigate the migration and transformation of substances during the pyrolysis of polyvinyl chloride (PVC) plastic from 200 °C to 900 °C with heating rates of 5, 50, 100, 150, and 200 K min-1. Results show the first stage of weight loss is at 200 °C-360 °C, where the dehydrochlorination of PVC mainly occurred, accompanied by the formation of conjugated double bonds and a small number of hydrocarbon compounds. The second stage of weight loss is at 360 °C-550 °C, where the breakage and rearrangement of the long polyethene chain may occur. Kinetics analysis shows the higher activation energy value is in the second stage, which indicates that the second stage reaction is less likely to occur and the Flynn-Wall-Ozawa method is more suitable for the study of plastic pyrolysis kinetics. This study suggests that second pollutants can be minimized during controllable pyrolysis.

Ionic Hydrogels Based Wearable Sensors to Monitor the Solar Radiation Dose for Vitamin D Production and Sunburn Prevention.

Wearable solar radiation sensors based on ionic hydrogels are facilely prepared to simultaneously monitor the radiation dose for the production of vitamin D and the prevention of sunburn. Tetramethylethylenediamine (TEMED) is neutralized with acrylic acid (AA) to obtain tetramethylethylenediamine acrylate (TEMEDA), which is further polymerized with acrylamide by a free radical reaction. By simply adding MB or NR during the polymerization, the final obtained ionic hydrogels can indicate solar radiation. Due to the extent of discoloration, the discoloration speed of MB and NR is correlated to the radiation dose. This wearable sensor can indicate the solar radiation dose required by the human body to synthesize vitamin D through the discoloration of the ionized hydrogel of MB, whereas those with NR are able to illustrate the threshold of radiation dose that causes potential skin hurt. Therefore, the benefit and drawback of solar radiation can be well balanced by optimizing the exposure time to solar irradiation. In addition, polyurethane cross-linked with a thermoresponsive coating is used as band for this wearable sensor. Due to the hydrophilicity below its transition temperature, the cross-linked band possesses the easy cleaning capability of stains after the daily wear. Such type of wearable sensor can be broadly used for monitoring the solar radiation, especially in outdoor activities.

An Efficient Carbon-Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway.

The emergence of nanocarriers solves the problems of antitumor drugs such as non-targeting, huge side effects, etc., and has been widely used in tumor therapy. Some kinds of antitumor drugs such as doxorubicin (DOX) mainly act on the nucleic acid causing DNA damage, interfering with transcription, and thereby disrupting or blocking the process of cancer cell replication. Herein, a new nanodrug delivery system, the carbon-based nanomaterials (CBNs)-Pluronic F127-DOX (CPD), is designed by using CBNs as a nanocarrier for DOX. As a result, the tumor growth inhibition rate of CPD group is as high as 79.42 ± 2.83%, and greatly reduces the side effects. The targeting rate of the CPD group of DOX in the tumor nucleus is 36.78%, and the %ID/g in tumor tissue is 30.09%. The CPD regulates the expression levels of Caspase-3, p53, and Bcl-2 genes by increasing intracellular reactive oxygen species (ROS) levels and reducing mitochondrial membrane potential, which indicates that mitochondrial-mediated pathways are involved in apoptosis. The CPD nanodrug delivery system increases the effective accumulation of DOX in tumor cell nuclei and tumor tissues, and generates massive ROS, thereby inhibiting tumor growth in vivo, representing a promising agent for anticancer applications.

Finite-difference and integral schemes for Maxwell viscous stress calculation in immersed boundary simulations of viscoelastic membranes.

The immersed boundary method (IBM) has been frequently utilized to simulate the motion and deformation of biological cells and capsules in various flow situations. Despite the convenience in dealing with flow-membrane interaction, direct implementation of membrane viscosity in IBM suffers severe numerical instability. It has been shown that adding an artificial elastic element in series to the viscous component in the membrane mechanics can efficiently improve the numerical stability in IBM membrane simulations. Recently Li and Zhang (Int J Numer Methods Biomed Eng 35:e3200, 2019) proposed a finite-difference method for calculating membrane viscous stress. In the present paper, two new schemes are developed based on the convolution integral expression of the Maxwell viscoelastic element. We then conduct several tests for the accuracy, stability, and efficiency performances of these three viscous stress schemes. By studying the behavior of a one-dimensional Maxwell element under sinusoidal deformation, we find that a good accuracy can be achieved by selecting an appropriate relaxation time. The twisting sphere tests confirm that, compared to the numerical errors induced by other components in capsule simulations, such as the finite element method for membrane discretization and IBM for flow-membrane interaction, the errors from the viscous stress calculation are negligible. Moreover, extensive simulations are conducted for the dynamic deformation of a spherical capsule in shear flow, using different numerical schemes and various combinations of the artificial spring constants and calculation frequency for the membrane viscous stress calculation. No difference is observed among the results from the three schemes; and these viscous stress schemes require very little extra computation time compared to other components in IBM simulations. The simulation results converge gradually with the increase in the artificial spring stiffness; however, a threshold value exists for the spring stiffness to maintain the numerical stability. The viscous stress calculation frequency has no apparent influence on the calculation results, but a large frequency number can cause the simulation to collapse. We therefore suggest to calculate the membrane viscous stress at each simulation time step, such that a better numerical stability can be achieved. The three numerical schemes have nearly identical performances in all aspects, and they can all be utilized in future IBM simulations of viscoelastic membranes.

Improving Longitudinal Transversal Relaxation Of Gadolinium Chelate Using Silica Coating Magnetite Nanoparticles.

INTRODUCTION AND OBJECTIVE: Precisely and sensitively diagnosing diseases especially early and accurate tumor diagnosis in clinical magnetic resonance (MR) scanner is a highly demanding but challenging task. Gadolinium (Gd) chelate is the most common T 1 magnetic resonance imaging (MRI) contrast agent at present. However, traditional Gd-chelates are suffering from low relaxivity, which hampers its application in clinical diagnosis. Currently, the development of nano-sized Gd based T 1 contrast agent, such as incorporating gadolinium chelate into nanocarriers, is an attractive and feasible strategy to enhance the T 1 contrast capacity of Gd chelate. The objective of this study is to improve the T 1 contrast ability of Gd-chelate by synthesizing nanoparticles (NPs) for accurate and early diagnosis in clinical diseases. METHODS: Reverse microemulsion method was used to coat iron oxide (IO) with tunable silica shell and form cores of NPs IO@SiO2 at step one, then Gd-chelate was loaded on the surface of silica-coated iron oxide NPs. Finally, Gd-based silica coating magnetite NPs IO@SiO2-DTPA-Gd was developed and tested the ability to detect tumor cells on the cellular and in vivo level. RESULTS: The r 1 value of IO@SiO2-DTPA-Gd NPs with the silica shell thickness of 12 nm was about 33.6 mM-1s-1, which was approximately 6 times higher than Gd-DTPA, and based on its high T 1 contrast ability, IO@SiO2-DTPA-Gd NPs could effectively detect tumor cells on the cellular and in vivo level. CONCLUSION: Our findings revealed the improvement of T 1 relaxation was not only because of the increase of molecular tumbling time caused by the IO@SiO2 nanocarrier but also the generated magnetic field caused by the IO core. This nanostructure with high T 1 contrast ability may open a new approach to construct high-performance T 1 contrast agent.

Evaluation of a polyvinyl alcohol-alginate based hydrogel for precise 3D bioprinting.

In this study, we designed a polyvinyl alcohol (PVA)-alginate based hydrogel and evaluated its cytocompatibility and printability. The samples were fabricated by 3D printing using a freeze-thaw process. The scanning electron microscope, material testing machine, rheometer, and cell counting kit-8 assay were used to examine the morphology, mechanical properties, rheological properties, and cytocompatiblity of the scaffolds, respectively. The mechanical strength, cytocompatiblity, crosslinking time, and printability were remarkably improved with the use of PVA. To sum up, our data suggest that hybrid bio-ink is more appropriate for precise 3D bioprinting due to its rapid prototyping capability and better cytocompatibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2944-2954, 2018.

Glycemic control and adipokines after periodontal therapy in patients with Type 2 diabetes and chronic periodontitis.

The mechanism by which chronic periodontitis (CP) affects type 2 diabetes (T2DM) remains unclear. Therefore, the aim of this study is to evaluate the effects of periodontal therapy (PT) on the glycemic control and adipokines of patients with T2DM and CP with the purpose of elucidating the possible mechanisms by which CP influences T2DM. Forty-four patients with T2DM and CP were randomly divided into two groups according to whether they underwent PT. Periodontal status, blood glucose, and the levels of serum tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), adiponectin (APN), and fibroblast growth factor-21 (FGF-21) were measured at baseline and after 3 months. The results revealed that the probing depth (PD) and attachment loss (AL) were significantly improved, the serum levels of TNF-α and IL-6 were significantly decreased, and APN and FGF-21 exhibited substantial increases in the intervention group after 3 months (p < 0.05), whereas no significant changes were observed in the control group. The glycated hemoglobin (HbA1c) levels in both groups decreased significantly after 3 months compared with baseline (p < 0.05), but the intervention group exhibited a significantly greater change (p < 0.05). In conclusion, PT may relieve periodontal inflammation, which causes a reduction of insulin-antagonizing adipokines and an increase in insulin-sensitizing adipokines, thereby eliciting an improvement in glycemic control.

TiAl6V4 particles promote osteoclast formation via autophagy-mediated downregulation of interferon-beta in osteocytes.

Wear debris-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the medium and long term. Although osteocytes are the most abundant cells in bone and make direct contact with implants, the interaction between osteocytes and wear debris remains largely unknown. In the present study, we investigated the effect of TiAl6V4 alloy particles (TiPs) on osteocytes and the subsequent effects on osteoclast formation. Our study demonstrated that osteocyte-conditioned medium (CM) inhibited osteoclast differentiation from bone marrow monocytes (BMMs) to osteoclasts. However, TiPs attenuated this inhibitory effect. The expression of several osteoclastogenesis-associated factors, including receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), nitric oxide (NO) and interferon-beta (IFN-ß), was examined, and we found that TiPs markedly decreased the expression of IFN-ß, but not the other factors. In an osteoclastogenesis assay, our results suggested that the downregulation of IFN-ß mediated the stimulatory effect of TiPs on osteoclastogenesis. Additional evidence suggested that TiPs decreased the expression of IFN-ß in osteocytes via macroautophagy (hereinafter referred to as "autophagy"). Moreover, inhibiting autophagy with Atg5 siRNA prevented the increase in osteoclastogenesis induced by TiPs. Collectively, these results suggested a possible mechanism underlying wear debris-induced osteolysis. STATEMENT OF SIGNIFICANCE: For the first time, our study demonstrated that Ti-alloy particles attenuated the inhibitory effect of osteocytes-conditioned medium on osteoclast formation. With an osteoclastogenesis assay, we found that the downregulation of IFN-ß in osteocytes mediated the promoting effect of TiPs on osteoclast formation. Furthermore, our results suggested that TiPs-induced autophagy mediated the downregulation of IFN-ß in osteocytes. Inhibition of autophagy recovered the expression of IFN-ß and ameliorated the promoting effect of TiPs on osteoclast formation. Collectively, these findings suggest a possible mechanism underlying wear debris-induced osteolysis and identified autophagy inhibition in osteocytes as a potential therapeutic approach for wear debris induced osteolysis.

Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-beta1 for chondrocytes proliferation.

Cartilage defects as a result of disease or injury have a very limited ability to heal spontaneously. Recently, tissue engineering and local therapeutic gene delivery systems have been paid much attention in the cartilage natural healing process. Gene-activated matrix (GAM) blends these two strategies, serving as local bioreactor with therapeutic agents expression and also providing a structural template to fill the lesion defects for cell adhesion, proliferation and synthesis of extracellular matrix (ECM). In the current study, we used chitosan-gelatin complex as biomaterials to fabricate three-dimensional scaffolds and plasmid DNA were entrapped in the scaffolds encoding transforming growth factor-beta1 (TGF-beta1), which has been proposed as a promoter of cartilage regeneration for its effect on the synthesis of matrix molecules and cell proliferation. The plasmid DNA incorporated in the scaffolds showed a burst release in the first week and a sustained release for the other 2 weeks. The gene transfectd into chondrocytes expresses TGF-beta1 protein stably in 3 weeks. The histological and immunohistochemical results confirmed that the primary chondrocytes cultured into the chitosan-gelatin scaffold maintained round and owned characters of high secretion of specific ECM. From this study, it can be concluded that this gene-activated chitosan-gelatins matrix has a potential in the application of cartilage defects regeneration.

Patient-Derived Human Induced Pluripotent Stem Cells From Gingival Fibroblasts Composited With Defined Nanohydroxyapatite/Chitosan/Gelatin Porous Scaffolds as Potential Bone Graft Substitutes.

UNLABELLED: Human embryonic stem cells and adult stem cells have always been the cell source for bone tissue engineering. However, their limitations are obvious, including ethical concerns and/or a short lifespan. The use of human induced pluripotent stem cells (hiPSCs) could avoid these problems. Nanohydroxyapatite (nHA) is an important component of natural bone and bone tissue engineering scaffolds. However, its regulation on osteogenic differentiation with hiPSCs from human gingival fibroblasts (hGFs) is unknown. The purpose of the present study was to investigate the osteogenic differentiation of hiPSCs from patient-derived hGFs regulated by nHA/chitosan/gelatin (HCG) scaffolds with different nHA ratios, such as HCG-111 (1 wt/vol% nHA) and HCG-311 (3 wt/vol% nHA). First, hGFs were reprogrammed into hiPSCs, which have enhanced osteogenic differentiation capability. Second, HCG-111 and HCG-311 scaffolds were successfully synthesized. Finally, hiPSC/HCG complexes were cultured in vitro or subcutaneously transplanted into immunocompromised mice in vivo. The osteogenic differentiation effects of two types of HCG scaffolds on hiPSCs were assessed for up to 12 weeks. The results showed that HCG-311 increased osteogenic-related gene expression of hiPSCs in vitro proved by quantitative real-time polymerase chain reaction, and hiPSC/HCG-311 complexes formed much bone-like tissue in vivo, indicated by cone-beam computed tomography imaging, H&E staining, Masson staining, and RUNX-2, OCN immunohistochemistry staining. In conclusion, our study has shown that osteogenic differentiation of hiPSCs from hGFs was improved by HCG-311. The mechanism might be that the nHA addition stimulates osteogenic marker expression of hiPSCs from hGFs. Our work has provided an innovative autologous cell-based bone tissue engineering approach with soft tissues such as clinically abundant gingiva. SIGNIFICANCE: The present study focused on patient-personalized bone tissue engineering. Human induced pluripotent stem cells (hiPSCs) were established from clinically easily derived human gingival fibroblasts (hGFs) and defined nanohydroxyapatite/chitosan/gelatin (HCG) scaffolds. hiPSCs derived from hGFs had better osteogenesis capability than that of hGFs. More interestingly, osteogenic differentiation of hiPSCs from hGFs was elevated significantly when composited with HCG-311 scaffolds in vitro and in vivo. The present study has uncovered the important role of different nHA ratios in HCG scaffolds in osteogenesis induction of hiPSCs derived from hGFs. This technique could serve as a potential innovative approach for bone tissue engineering, especially large bone regeneration clinically.

Re-polarizing Myeloid-derived Suppressor Cells (MDSCs) with Cationic Polymers for Cancer Immunotherapy.

Our evolving understandings of cell-material interactions provide insights for using polymers to modulate cell behaviour that may lead to therapeutic applications. It is known that in certain cancers, myeloid-derived suppressor cells (MDSCs) play vital roles in promoting tumour progression, chiefly because of their 'alternatively activated' (or M2) phenotype that orchestrates immunosuppression. In this study, we demonstrated that two cationic polymers - cationic dextran (C-dextran) and polyethyleneimine (PEI) - could directly remodel these cells into an anti-tumour, 'classically activated' (or M1) phenotype, thereby stimulating these cells to express tumouricidal cytokines, reactivating the T cell functions, and prolonging the lifespan of the mice model. Our investigations with knock-out mice further indicate that the functions of these cationic polymers require the involvement of toll-like receptor 4-mediated signalling. Taken together, our study suggests that these cationic polymers can effectively and directly re-polarize MDSCs from an immunosuppressive characteristic to an anti-tumour phenotype, leading to successful restoration of immune surveillance in the tumour microenvironment and elimination of tumour cells. Our findings may have immediate impact on further development of polymer-based therapeutics for cancer immunotherapy.

Prevalence of and risk factors for the occurrence of symptomatic osteoarthritis in rural regions of Shanxi Province, China.

AIM: To determine the prevalence of symptomatic osteoarthritis (OA) in rural regions of Shanxi Province, China, and to identify factors increasing the prevalence of OA. METHOD: Residents over 16 years of age of targeted towns and villages in rural regions of Shanxi Province were sampled using a stratified multi-stage cluster method. Those exhibiting symptoms of rheumatism were referred to rheumatologists and those in whom rheumatism was suspected were X-rayed within 10 days of interview. OA was diagnosed by consensus (two or three rheumatologists). Factors associated with the presence of OA were identified. RESULTS: A total of 7126 permanent residents were surveyed and 1734 (24.3%) had OA. Knee OA was the most prevalent form of OA (13.8%), followed by lumbar (7.4%), cervical (3.4%), hand (3.3%), shoulder (3.0%), elbow (2.9%), ankle (0.7%), hip (0.6%), wrist (0.5%), thoracic (0.5%) and foot OA (0.5%). All of knee, ankle, shoulder and hand OA exhibited a gender bias. Advanced age, a sweet tooth, poor home ventilation, poor home heating, separation, divorce, or death of a partner, low-grade occupation, low educational level, high body mass index and the presence of concomitant cardiovascular disease, were associated with the presence of OA. CONCLUSION: Symptomatic OA is very prevalent in rural regions of Shanxi Province. Many factors increase the prevalence of the condition. Primary and secondary prevention programs seeking to improve living conditions, to reduce obesity, and to effectively treat concomitant cardiovascular disease, are required.

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 µg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.