Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis.

BACKGROUND: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration, serious adverse reactions during long-term administration. To achieve better treatment, reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. RESULTS: The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was - 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo biodistribution experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility. CONCLUSION: The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

Lithium doped silica nanospheres/poly(dopamine) composite coating on polyetheretherketone to stimulate cell responses, improve bone formation and osseointegration.

Osseointegration is crucial for early fixation as well as long-term success of orthopedic implants. Bioactive composite containing lithium doping silica nanospheres (LSNs) and poly(dopamine) (PDA) were coated on polyetheretherketone (PK) surface (LPPK), and effects of the LSNs/PDA composite (LPC) coating on the biological properties of LPPK were assessed both in vitro and in vivo. Results showed that LPPK with improved bioactivity remarkably promoted apatite mineralization in simulated body fluid (SBF) compared with PDA coated on PK (PPK) and PK. Moreover, the LPPK remarkably stimulated rat bone marrow stromal cells (rBMSCs) responses compared with PPK and PK. Furthermore, the LPPK significantly promoted bone tissues responses in vivo compared with PPK and PK. It could be suggested that the improvements of cells and bone tissues responses were attributed to the surface characteristics of the bioactive LPC coating on LPPK. The LPPK would be a great candidate for orthopedic and dental applications.

Characteristics and Comparisons of Morphometric Measurements and Computed Tomography Hounsfield Unit Values of C2 Laminae for Translaminar Screw Placement Between Patients With and Without Basilar Invagination.

OBJECTIVE: Patients with basilar invagination (BI) had high incidences of vertebral variations and high-riding vertebral artery (HRVA) that might restrict the use of pedicle or pars screw and increase the use of translaminar screw on axis. Here, we conducted a radiographic study to investigate the feasibility of translaminar screws and the bone quality of C2 laminae in patients with BI, which were compared with those without BI as control to provide guidelines for safe placement. METHODS: In this study, a total of 410 patients (205 consecutive patients with BI and 205 matched patients without BI) and 820 unilateral laminae of the axis were included at a 1:1 ratio. Comparisons with regard to insertion parameters (laminar length, thickness, angle, and height) for C2 translaminar screw placement and Hounsfield unit (HU) values for the assessment of the appropriate bone mineral density of C2 laminae between BI and control groups were performed. Besides, the subgroup analyses based on the Goel A and B classification of BI, HRVA, atlas occipitalization, and C2/3 assimilation were also carried out. Furthermore, the factors that might affect the insertion parameters and HU values were explored through multiple linear regression analyses. RESULTS: The BI group showed a significantly smaller laminar length, thickness, height, and HU value than the control group, whereas no significant difference was observed regarding the laminar angle. By contrast, the control group showed significantly higher rates of acceptability for unilateral and bilateral translaminar screw fixations than the BI group. Subgroup analyses showed that the classification of Goel A and B, HRVA, atlas occipitalization, and C2/3 assimilation affected the insertion parameters except the HU values. Multiple linear regression indicated that the laminar length was significantly associated with the male gender (B = 0.190, p < 0.001), diagnoses of HRVA (B = -0.109, p < 0.001), Goel A (B = -0.167, p < 0.001), and C2/3 assimilation (B = -0.079, p = 0.029); the laminar thickness was significantly associated with the male gender (B = 0.353, p < 0.001), diagnoses of HRVA (B = -0.430, p < 0.001), Goel B (B = -0.249, p = 0.026), and distance from the top of odontoid to the Chamberlain line (B = -0.025, p = 0.003); laminar HU values were significantly associated with age (B = -2.517, p < 0.001), Goel A (B = -44.205, p < 0.001), Goel B (B = -25.704, p = 0.014), and laminar thickness (B = -11.706, p = 0.001). CONCLUSION: Patients with BI had narrower and smaller laminae with lower HU values and lower unilateral and bilateral acceptability for translaminar screws than patients without BI. Preoperative 3-dimensional computed tomography (CT) and CT angiography were needed for BI patients.

Acoustical scattering by multilayer spherical elastic scatterer containing electrorheological layer.

A computational procedure for analyzing acoustical scattering by multilayer concentric spherical scatterers having an arbitrary mixture of acoustic and elastic materials is proposed. The procedure is then used to analyze the scattering by a spherical scatterer consisting of a solid shell and a solid core encasing an electrorheological (ER) fluid layer, and the tunability in the scattering characteristics afforded by the ER layer is explored numerically. Tunable scatterers with two different ER fluids are analyzed. One, corn starch in peanut oil, shows that a significant increase in scattering cross-section is possible in moderate frequencies. Another, fine poly-methyl methacrylate (PMMA) beads in dodecane, shows only slight change in scattering cross-sections overall. But, when the shell is thin, a noticeable local resonance peak can appear near ka=1, and this resonance can be turned on or off by the external electric field.

Molecular characteristics and phylogenetic analysis of N gene of human derived rabies virus.

OBJECTIVE: To investigate the relationship between the molecular characteristics and phylogenetic evolution of rabies N gene. METHODS: Saliva samples were collected from rabies cases, and RT-PCR was used to amplify the N gene of rabies virus with the specific primers. The amplifying product of RT-PCR was cloned to pUCm-T vector and transformed into E.coli XL1-Blue and then the blue-white selection, PCR screening and gene sequencing were carried out to identify the positive clones. Finally, ExPASy and other bioinformatics software were used to analyze and predict the structure and biological characteristics of the N genome. RESULTS: The amplification product of RT-PCR was 1 353 bp, the recombinant plasmid pUCm-T/N was constructed, the whole length of the N gene open reading frame was composed of 1 353 nucleotide residues to code 450 amino acids (20 kinds), the accession number submitted to the Genbank was HM756692, its sequence homology of nucleotides and amino acids compared with the vaccine strain CTN-1-V was 90% and 99% respectively. The evolutionary analysis showed that the isolated strain belonged to genotype I with certain geographic regionality. CONCLUSION: The characteristics investigation and bioinformatics analysis of Hunan0806 N gene will provide fundamental data to reveal the significance of the N gene characteristics for rabies epidemiology and its prevention & control.

Changes in salivary chromogranin A levels in adults with atopic dermatitis are correlated with changes in their condition.

Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Symptoms of stress-induced AD are common in clinical practise. Salivary chromogranin A (CgA) level has research value as a possible index related to a patient's psychological stress. Using saliva, which is easily collectable, we compared two assessments of the severities of AD and stress with the levels of stress proteins in the saliva of 30 patients with AD in the Department of Dermatology of Shimane University between April 2015 and May 2017. The severities of AD and stress were assessed using the Scoring Atopic Dermatitis (SCORAD) score and State-Trait Anxiety Inventory score, respectively. Additionally, the assessments included those of personality using the Tokyo University Egogram (TEG)-II score and quality of life using the Dermatology Life Quality Index score. Simultaneously, we measured their salivary CgA levels. The change in salivary CgA per protein in patients with AD was correlated with their changes in SCORAD score (correlation coefficient, r = 0.596, P = 0.001) and objective SCORAD (r = 0.608, P < 0.001). The changes in CgA per protein correlated with those in TEG-II A (r = 0.370, P = 0.022), while the changes in SCORAD score correlated with those in DLQI (r = 0.309, P = 0.048). Our results suggest that changes in a patient's condition are reflective of the changes in the patient's stress. The changes in salivary CgA level in patients with AD correlated with the changes in their condition.

The effects of surface bioactivity and sustained-release of genistein from a mesoporous magnesium-calcium-silicate/PK composite stimulating cell responses in vitro, and promoting osteogenesis and enhancing osseointegration in vivo.

The surface of a mesoporous magnesium-calcium-silicate (m-MCS)/polyetheretherketone (PK) composite (MPC) was modified by sand blasting, and genistein (GS) was loaded inside the nanopores of the m-MCS on the modified MPC (MPCm) surface. The results showed that compared with MPC, the surface roughness and hydrophilcity of MPCm obviously improved with more m-MCS exposed on its surface. Moreover, no obvious differences in surface roughness and hydrophilcity were found between MPCm and GS loaded MPCm (MPCm-Ge), and both of them possessed an improved apatite mineralization ability in simulated body fluid solution (SBF) compared with MPC, indicating excellent surface bioactivity. Moreover, the MPCm obviously stimulated the adhesion, proliferation, differentiation and gene expressions of MC3T3-E1 cells compared with MPC, and the sustained-release of GS from the MPCm-Ge surface further significantly promoted the cell proliferation, differentiation and gene expression. According to the Micro-CT, histological and SEM analysis, the results demonstrated that the MPCm obviously improved osteogenesis and enhanced osseointegration in vivo compared with MPC, and the release of GS from the MPCm-Ge surface further significantly improved osteogenesis and enhanced osseointegration. In summary, the significant promotion of cell responses in vitro, and the improvements of osteogenesis and the enhancement of osseointegration in vivo were attributed to the effects of surface bioactivity and GS sustained-release from the MPCm-Ge surface. Therefore, MPCm-Ge would be a potential candidate for orthopedic and dental applications.

Burkitt Lymphoma Presented as Acute Lower Back Pain and Revealed by 18F-NaF PET/CT.

A 15-year-old man with acute lower back pain for 7 days underwent F-NaF PET/CT to determine the cause of his symptoms. The PET images revealed irregularly increased F activity in the L1 vertebral body without definite sclerotic changes on CT. However, the corresponding CT images revealed an adjacent paravertebral mass extending into the vertebral foramen without elevated activity on PET. A diagnosis of Burkitt lymphoma was made after pathological examination.

Intense 99mTc-MDP and 18F-NaF Activity in Long-standing Subcutaneous Implants.

A 64-year-old woman with a newly diagnosed left breast cancer underwent a presurgical Tc-MDP whole-body imaging, which showed 1 intense activity in the midline upper abdomen and another overlapping the upper thoracic spine. An F-NaF PET/CT scan performed a day later also revealed the elevated activity in the same regions. The activity corresponded to calcified subcutaneous implants, which were placed there more than 30 years ago.

Unexpected Detection of Urinary Bladder Cancer on Dual Phase 18F-NaF PET/CT in a Patient With Back Pain.

A 72-year-old man underwent F-NaF PET/CT to evaluate causes of lower back pain. The PET images revealed multiple foci of increased activity in several vertebral bodies, which might account for the patient's symptoms. In addition, the CT image revealed partially calcified soft tissue mass in the posterior wall of the urinary bladder, which was photopenic relative to the radioactive urine on early PET images but became intense on delayed PET images. The diagnosis of transitional cell carcinoma was made pathologically after a transurethral resection of the mass.

Unexpected Pregnancy Revealed on 18F-NaF PET/CT.

A 48-year-old illiterate woman who is congenitally deaf and mute underwent 18F-NaF PET/CT study to evaluate bone metastases from newly diagnosed breast cancer. Unexpectedly, a fetus in early second trimester was noted on CT images. In addition, subtle 18F-NaF uptake by the fetus could also be observed.

Elevated 99mTc-MDP and 18F-NaF Uptake in a Bladder Stone.

An 82-year-old man with known Eddison disease, osteoporosis, and a right buttock soft tissue mass underwent Tc-MDP bone scintigraphy with SPECT/CT and F-NaF PET/CT, both of which showed elevated uptake in a bladder stone.

Significant 99mTc-MDP but Unimpressive 18F-NaF Gastric Activity in a Patient With Multiple Myeloma.

A 69-year-old man with a history of low back pain for more than 4 months underwent Tc-MDP bone scan to determine the cause of the symptoms. In addition to the osseous lesions, significant activity in the stomach wall was noted. However, a subsequent F-NaF PET/CT only revealed bone lesion without increased activity in the stomach wall. The cause of the back pain was eventually confirmed due to multiple myeloma.