A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the ...impact of circulating exosomes on HCC development and recurrence. One‐shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha‐fetoprotein (AFP), but exosome‐free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR‐92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR‐92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR‐92b. The hepatoma‐derived exosomal miR‐92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell‐mediated cytotoxicity. Furthermore, higher expression of miR‐92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma‐derived exosomal miR‐92b. The value of circulating exosomal miR‐92b may predict the risk of posttransplant HCC recurrence.
This study demonstrates the impact of circulating exosomes on liver cancer development in rats, explores functional roles of exosomal miR‐92b in the tumor microenvironment, and verifies its clinical value for early prediction of posttransplant hepatocellular carcinoma recurrence.
A high‐sensitivity and low‐power theranostic nanosystem that combines with synergistic photothermal therapy and surface‐enhanced Raman scattering (SERS) mapping is constructed by mesoporous silica ...self‐assembly on the reduced graphene oxide (rGO) nanosheets with nanogap‐aligned gold nanoparticles (AuNPs) encapsulated and arranged inside the nanochannels of the mesoporous silica layer. Rhodamine 6G (R6G) as a Raman reporter is then encapsulated into the nanochannels and anti‐epidermal growth factor receptor (EGFR) is conjugated on the nanocomposite surface, defined as anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G, where PEG is polyethylene glycol and CPSS is carbon porous silica nanosheets. SERS spectra results show that rGO@CPSS‐Au‐R6G enhances 5 × 106 magnification of the Raman signals and thus can be applied in the noninvasive cell tracking. Furthermore, it displays high sensitivity (detection limits: 10−8m R6G solution) due to the “hot spots” effects by the arrangements of AuNPs in the nanochannels of mesoporous silica. The highly selective targeting of overexpressing EGFR lung cancer cells (A549) is observed in the anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G, in contrast to normal cells (MRC‐5). High photothermal therapy efficiency with a low power density (0.5 W cm−2) of near‐infrared laser can be achieved because of the synergistic effect by conjugated AuNPs and rGO nanosheets. These results demonstrate that the anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G is an excellent new theranostic nanosystem with cell targeting, cell tracking, and photothermal therapy capabilities.
By integrating targeting antibody (anti‐epidermal growth factor receptor), hot‐spots between arrayed gold nanoparticles and surface‐enhanced Raman scattering mapping image, a controllable porous silica/carbon nanostructure is developed. Supported on a reduced graphene oxide substrate to achieve real‐time diagnosis with synergistic photothermal effects, on‐demand eradication of tumor cells in vitro is enabled.
Semiconductor crystals have generally shown facet‐dependent electrical, photocatalytic, and optical properties. These phenomena have been proposed to result from the presence of a surface layer with ...bond‐level deviations. To provide experimental evidence of this structural feature, synchrotron X‐ray sources are used to obtain X‐ray diffraction (XRD) patterns of polyhedral cuprous oxide crystals. Cu2O rhombic dodecahedra display two distinct cell constants from peak splitting. Peak disappearance during slow Cu2O reduction to Cu with ammonia borane differentiates bulk and surface layer lattices. Cubes and octahedra also show two peak components, while diffraction peaks of cuboctahedra are comprised of three components. Temperature‐varying lattice changes in the bulk and surface regions also show shape dependence. From transmission electron microscopy (TEM) images, slight plane spacing deviations in surface and inner crystal regions are measured. Image processing provides visualization of the surface layer with depths of about 1.5–4 nm giving dashed lattice points instead of dots from atomic position deviations. Close TEM examination reveals considerable variation in lattice spot size and shape for different particle morphologies, explaining why facet‐dependent properties are emerged. Raman spectrum reflects the large bulk and surface lattice difference in rhombic dodecahedra. Surface lattice difference can change the particle bandgap.
High‐resolution X‐ray diffraction patterns reveal bulk and surface layer components for polyhedral Cu2O crystals, while transmission electron microscopy analysis provides first visual evidence of the surface layer contributing to their various facet‐dependent properties. The surface layer can affect Raman spectra and tune the crystal bandgap.
To determine the association between combined lifestyle factors, including healthy diet, moderate alcohol consumption, non-smoking, physical activity, and optimal weight, and cardiovascular disease ...(CVD) risk among younger and older adults. We conducted a literature search using PubMed, EMBASE, Cochrane Library, and EBSCO databases up to November 30, 2019 and performed dose-response analysis, subgroup analysis and meta-regression with odds ratios and 95% confidence intervals (CIs). Twenty cohort studies involving 1,090,261 participants with 46,288 cardiovascular events and mean follow-up duration of 12.33 years were included. Compared with the group with the lowest number of healthy lifestyle factors, the group with the highest number had lower CVD risk pooled hazard ratio, 0.37 (95% CI 0.31-0.43). With age as an effect modifier, the lifetime risk of CVD was 0.31 (95% CI 0.24-0.41) at age 37.1-49.9 years, 0.36 (95% CI 0.30-0.45) at age 50.0-59.9 years and 0.49 (95% CI 0.38-0.63) at age 60.0-72.9 years. The hazard ratio of CVD significantly increased from 37.1 to 72.9 years of age slope in multivariate meta-regression: 0.01 (95% CI < 0.001-0.03; p = 0.042). Younger adults have more cardiovascular benefits from combined healthy lifestyle factors.
Objectives
The objective of this study was to determine global changes in gene expression with next generation sequencing (NGS) in order to assess the biological effects of orthodontic tooth movement ...(OTM) on alveolar bone in a rat model.
Materials and Methods
Thirty‐five Wistar rats (age 14 weeks) were used in the study. The OTM was performed using closed coil Nickel–Titanium spring to apply a mesial force on maxillary first molars of 8–10 g. Three hours, 1, 3, 7 and 14 days after the placement of the appliance, rats were killed at each time point respectively. The alveolar bone, around left maxillary first molar, were excised on compression side. The samples were immediately frozen in liquid nitrogen for subsequent RNA extraction. Total RNA samples were prepared for mRNA sequencing using the Illumina kit. RNA‐Seq reads were aligned to the rat genomes using the STAR Aligner and bioinformatic analysis was performed.
Results
A total of 18 192 genes were determined. Day 1 has the highest number of differentially expressed genes (DEGs) observed with more upregulated than downregulated genes. A total of 2719 DEGs were identified to use as input for the algorithm. Six distinct clusters of temporal patterns were observed representing proteins that were differentially regulated indicating different expression kinetics. Principal component analysis (PCA) showed distinct clustering by time points and days 3, 7 and 14 share similar gene expression pattern.
Conclusions
Distinct gene expression pattern was observed at different time points studied. Hypoxia, inflammation and bone remodelling pathways are major mechanisms behind OTM.
A novel photo‐responsive drug carrier that doubles as a photothermal agent with a nanocookie‐like structure is constructed by coating amorphous carbon on a mesoporous silica support self‐assembled on ...a sheet of reduced graphene oxide. With a large payload (0.88 mmolg−1) of a hydrophobic anticancer drug, (S)‐(+)‐camptothecin (CPT), nanocookies simultaneously provide a burst‐like drug release and intense heat upon near‐infrared exposure. Being biocompatible yet with a high efficiency for cell uptake, nanocookies have successfully eradicated subcutaneous tumors in 14 days following a single 5 min NIR irradiation without distal damage. These results demonstrate that the nanocookie is an excellent new delivery platform for local, on‐demand, NIR‐responsive, combined chemotherapy/hyperthermia for tumor treatment and other biomedical applications.
Formed by a one‐pot, scalable emulsion method and triggered by near infrared irradiation, photosensitive nanoparticles with a silica/carbon nanostructure supported on a reduced graphene oxide substrate can control release of hydrophobic chemotherapy drugs with synergistic hyperthermia effects, eradicating tumor cells in vivo and in vitro on demand.
Aging is one of the major risk factors for degenerative joint disorders, including those involving the temporomandibular joint (TMJ). TMJ degeneration occurs primarily in the population over 65, ...significantly increasing the risk of joint discomfort, restricted joint mobility, and reduced quality of life. Unfortunately, there is currently no effective mechanism‐based treatment available in the clinic to alleviate TMJ degeneration with aging. We now demonstrate that intermittent administration of senolytics, drugs which can selectively clear senescent cells, preserved mandibular condylar cartilage thickness, improved subchondral bone volume and turnover, and reduced Osteoarthritis Research Society International (OARSI) histopathological score in both 23‐ to 24‐month‐old male and female mice. Senolytics had little effect on 4 months old young mice, indicating age‐specific benefits. Our study provides proof‐of‐concept evidence that age‐related TMJ degeneration can be alleviated by pharmaceutical intervention targeting cellular senescence. Since the senolytics used in this study have been proven relatively safe in recent human studies, our findings may help justify future clinical trials addressing TMJ degeneration in old age.
Senolytic drugs preserved mandibular condylar cartilage thickness, improved subchondral bone volume and turnover, and reduced pathologies in old mouse TMJs.
By mimicking natural photosynthesis, generating hydrogen through visible-light-driven splitting of water would be an almost ideal process for converting abundant solar energy into a usable fuel in an ...environmentally friendly and high-energy-density manner. In a search for efficient photocatalysts that mimic such a function, here we describe a series of cycloplatinated polymer dots (Pdots), in which the platinum complex unit is presynthesized as a comonomer and then covalently linked to a conjugated polymer backbone through Suzuki–Miyaura cross-coupling polymerization. On the basis of our design strategy, the hydrogen evolution rate (HER) of the cycloplatinated Pdots can be enhanced by 12 times in comparison to that of pristine Pdots under otherwise identical conditions. In comparison to the Pt-complex-blended counterpart Pdots, the HER of cycloplatinated Pdots is over 2 times higher than that of physically blended Pdots. Furthermore, enhancement of the photocatalytic reaction time with high eventual hydrogen production and low efficiency rolloff are observed by utilizing the cycloplatinated Pdots as photocatalysts. On the basis of their performance, our cyclometallic Pdot systems appear to be alternative types of promising photocatalysts for visible-light-driven hydrogen evolution.
Iron‐oxide‐containing double emulsion capsules carrying both hydrophilic and hydrophobic therapeutic molecules can deliver drugs and energy on demand in vivo. Magneto‐chemotherapy/hyperthermia ...involves a burst‐like release of hydrophilic doxorubicin and hydrophobic paclitaxel, remotely triggered by a high frequency magnetic field, which also releases energy via internalized iron oxide nanoparticles, all contributing to cell kill.
Display omitted
•Development of a simple solid-state synthesis for preparation of biofunctional fluorescent carbon quantum dots (CQDs).•Mannose (Man) and folic acid (FA) were self-functionalized to ...CQDs.•Man–CQDs can be used for selective labeling of E. coli.•FA–CQDs are highly selective for folate receptor-overexpressing tumor cells.
We have developed a simple solid-state synthesis procedure to functionalize fluorescent carbon quantum dots (CQDs), using ammonium citrate as a carbon source and appropriate molecules as recognition ligands. Mannose and folic acid were used to modify CQDs to selectively label Escherichia coli (E. coli) and tumor cells, respectively. First, fluorescent-core CQDs (approximate size: 3nm) were synthesized through carbonization of ammonium citrate via dry heating. In the second step, CQDs were heated with mannose and folic acid to prepare mannose-functionalized CQDs (Man–CQDs) and folic acid-functionalized CQDs (FA–CQDs), respectively, through a dehydration reaction in the solid state. Solid-state synthesis of the self-functional CQDs is achievable without a coupling agent. We optimized the labeling efficiencies of self-functional Man–CQD and FA–CQD to cells by controlling the ratio of mannose or folic acid to CQDs, as well as the reaction temperature during synthesis. The solid-state synthesized Man–CQDs and FA–CQDs exhibited excitation-dependent fluorescence with excitation and emission maxima of 365 and 450nm, respectively, and a fluorescence quantum yield of approximately 9%. Man–CQDs can be used for selective labeling of E. coli and detection at concentrations as low as 100 colony forming units mL−1 in real samples (e.g., drinking water, apple juice, urine). Furthermore FA–CQDs are highly selective for labeling of folate receptor-overexpressing tumor cells. The synthesis of self-functional CQDs is simple, cost effective, and easily scaled up, and can be extended to the synthesis of various functional carbon nanomaterials, such as graphene oxide nanosheets, carbon nanotubes, fullerene nanoparticles and carbon nanodiamonds, with different ligands for other biolabeling applications and targeted therapies.
PDF
