The value of synthetic magnetic resonance imaging in the diagnosis and assessment of prostate cancer aggressiveness.

Background: Synthetic magnetic resonance imaging (SyMRI) is a fast, standardized, and robust novel quantitative technique that has the potential to circumvent the subjectivity of interpretation in prostate multiparametric magnetic resonance imaging (mpMRI) and the limitations of existing MRI quantification techniques. Our study aimed to evaluate the potential utility of SyMRI in the diagnosis and aggressiveness assessment of prostate cancer (PCA). Methods: We retrospectively analyzed 309 patients with suspected PCA who had undergone mpMRI and SyMRI, and pathologic results were obtained by biopsy or PCA radical prostatectomy (RP). Pathological types were classified as PCA, benign prostatic hyperplasia (BPH), or peripheral zone (PZ) inflammation. According to the Gleason Score (GS), PCA was divided into groups of intermediate-to-high risk (GS ≥4+3) and low-risk (GS ≤3+4). Patients with biopsy-confirmed low-risk PCA were further divided into upgraded and nonupgraded groups based on the GS changes of the RP results. The values of the apparent diffusion coefficient (ADC), T1, T2 and proton density (PD) of these lesions were measured on ADC and SyMRI parameter maps by two physicians; these values were compared between PCA and BPH or inflammation, between the intermediate-to-high-risk and low-risk PCA groups, and between the upgraded and nonupgraded PCA groups. The risk factors affecting GS grades were identified via univariate analysis. The effects of confounding factors were excluded through multivariate logistic regression analysis, and independent predictive factors were calculated. Subsequently, the ADC+Sy(T2+PD) combined models for predicting PCA risk grade or GS upgrade were constructed through data processing analysis. The diagnostic performance of each parameter and the ADC+Sy(T2+PD) model was analyzed. The calibration curve was calculated by the bootstrapping internal validation method (200 bootstrap resamples). Results: The T1, T2, and PD values of PCA were significantly lower than those of BPH or inflammation (P≤0.001) in both the PZ or transitional zone. Among the 178 patients with PCA, intermediate-to-high-risk PCA group had significantly higher T1, T2, and PD values but lower ADC values compared with the low-risk group (P<0.05), and the diagnostic efficacy of each single parameter was similar (P>0.05). The ADC+Sy(T2+PD) model showed the best performance, with an area under the curve (AUC) 0.110 [AUC =0.818; 95% confidence interval (CI): 0.754-0.872] higher than that of ADC alone (AUC =0.708; 95% CI: 0.635-0.774) (P=0.003). Among the 68 patients initially classified as PCA in the low-risk group by biopsy, PCA in the postoperative upgraded GS group had significantly higher T1, T2, and PD values but lower ADC values than did those in the nonupgraded group (P<0.01). In addition, the ADC+Sy(T2+PD) model better predicted the upgrade of GS, with a significant increase in AUC of 0.204 (AUC =0.947; 95% CI: 0.864-0.987) compared with ADC alone (AUC =0.743; 95% CI: 0.622-0.841) (P<0.001). Conclusions: Quantitative parameters (T1, T2, and PD) derived from SyMRI can help differentiate PCA from non-PCA. Combining SyMRI parameters with ADC significantly improved the ability to differentiate between intermediate-to-high risk PCA from low-risk PCA and could predict the upgrade of low-risk PCA as confirmed by biopsy.

Multi-wavelength unidirectional forward scattering properties of the arrow-shaped gallium phosphide nanoantenna.

An arrow-shaped gallium phosphide nanoantenna exhibits both near-field electric field enhancement and far-field unidirectional scattering, and the interference conditions involve electric and magnetic quadrupoles as well as toroidal dipoles. By using long-wavelength approximation and exact multipole decomposition, the interference conditions required for far-field unidirectional transverse light scattering and backward near-zero scattering at multiple wavelengths are determined. The near-field properties are excellent, as exemplified by large Purcell factors of 4.5×109 for electric dipole source excitation, 464.68 for magnetic dipole source excitation, and 700 V/m for the field enhancement factor. The degree of enhancement of unidirectional scattering is affected by structural parameters such as the angle and thickness of the nanoantenna. The arrow-shaped nanoantenna is an efficient platform to enhance the electric field and achieve high directionality of light scattering. Moreover, the nanostructure enables flexible manipulation of light waves and materials, giving rise to superior near-field and far-field performances, which are of great importance pertaining to the practicability and application potential of optical antennas in applications such as spectroscopy, sensing, displays, and optoelectronic devices.

Double-ring-disk hybrid nanostructures with slits for electric field enhancement.

Although noble metal nanoantennas have distinctive optical properties and local electric field enhancement, considerable non-radiative ohmic losses occur at the optical frequencies, consequently creating significant absorption and unwanted heating. Combining the plasmon mode of metal nanoantennas with the anapole mode of high refractive index dielectric materials offers a promising alternative to increase the electric field strength with minimal loss. Herein, a silicon disk with slots and two Au rings with a coupling mechanism are described. To elucidate the field enhancement mechanism, the near-field enhancement features and near-field electric field distributions are explored by a numerical simulation and multipole decomposition analysis. By opening the slit to generate high-intensity hot spots inside the disk, the electric field can be enhanced significantly, and nearby molecules can directly contact these hot spots. The resulting large field enhancement suggests significant applications to strong photon-exciton coupling and nonlinear photonics.

Transcriptomic Heterogeneity of Human Mesenchymal Stem Cells Derived from Bone Marrow, Dental Pulp, Adipose Tissue, and Umbilical Cord.

Compared with mesenchymal stem cells (MSCs) obtained from other tissue sources, those derived from umbilical cord (UC) tissue exhibit numerous advantages and vast potential for therapeutic applications. However, MSCs from different tissue sources are heterogeneous, and therefore, the therapeutic efficacy of UC-derived MSCs as a replacement for other tissue-derived MSCs needs to be studied. To better understand the distinctions between UC-derived MSCs and MSCs derived from other tissues, we conducted a transcriptome analysis of MSCs obtained from UC and three other tissues. Correlation analysis revealed the strongest correlation between UC-MSCs (UC-MSCs) and bone marrow-MSCs (BM-MSCs). Compared with UC-MSCs, the lower differentially expressed genes of BM-MSCs, dental pulp-MSCs (DP-MSCs), and adipose tissue-MSCs (AP-MSCs) were predominantly enriched in actin-related terms, while higher differentially expressed genes were predominantly enriched in immunological processes. We also analyzed the distribution of 34 frequently or highly expressed cell characterization molecules in BM-MSCs, DP-MSCs, AP-MSCs, and UC-MSCs. CD200 (FPKM >10) was only detected in UC-MSCs, while CD106 was detected in AD-MSCs and DP-MSCs (FPKM >10). The reliability of transcriptomic data analysis was verified by quantitative real-time PCR. Finally, we recommend the use of CD200, CD106, and other similar markers with unstable expression as benchmark molecules to monitor the proliferation and differentiation potential of MSCs. This study provides comprehensive insights into the heterogeneity between UC-MSCs and MSCs derived from other tissues, which can guide the therapeutic application of UC-MSCs.

Bis­enoxacin blocks alveolar bone resorption in rats with ovariectomy­induced osteoporosis.

Postmenopausal osteoporosis is a common systemic skeletal disease that is associated with estrogen­deficiency. Bone loss associated with bisphosphonates therapy can increase the risk of developing oral osteonecrosis. Recent studies have indicated that enoxacin may inhibit osteoclast formation and bone resorption via a different mechanism from that of bisphosphonates. Therefore, the authors hypothesized that the use of an enoxacin such as bis­enoxacin (BE) in association with bisphosphonates may be effective in the treatment of postmenopausal osteoporosis­associated alveolar bone resorption and reduce the risk of oral osteonecrosis by allowing the dose of bisphosphonates to be reduced. A total of 30 6­month­old female Sprague­Dawley rats were randomly assigned to five groups: The Sham, Vehicle, zoledronic acid (ZOL), low concentrations of BE (BE­L) and high concentrations of BE (BE­H) groups. The results demonstrated that the ZOL, BE­L and BE­H groups had an increased bone volume/tissue volume, trabecular thickness, mineral apposition rate, mineralizing surface/bone surface and a decreased trabecular separation when compared with the Vehicle group. The microscopic evaluation of histological sections clearly supported the results of the micro­computed tomography. The number of tartrate­resistant acid phosphatase­positive osteoclasts was markedly decreased in the ZOL, BE­L and BE­H groups, indicating that BE may inhibit osteoclast formation. The anti­resorptive effect in the BE­H group was close to or better than that exhibited by the ZOL group; however, this effect was poorer in the BE­L group. In conclusion, BE has the potential to block alveolar bone resorption resulting from ovariectomy­induced osteoporosis in rats in a dose­dependent manner.

Effects of oestrogen deficiency on the alveolar bone of rats with experimental periodontitis.

Periodontitis is an inflammatory disease characterized by loss of connective tissue and alveolar bone, and osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture. To date, the association between periodontitis and osteoporosis has remained to be fully elucidated. In the present study, an experimental rat model of periodontitis was used to explore the effects of oestrogen deficiency­induced osteoporosis on the maxillary alveolar bone. Forty­four female, six­month­old Sprague­Dawley rats were randomly divided into four groups: Control, ligature, ovariectomized (OVX), and OVX + ligature. One month after ovariectomy, rats in the ligature and OVX + ligature groups received ligatures on their first and second maxillary molars for 1 month. Fluorescent labelling was performed prior to sacrificing the animals. At the end of the experiment, the maxillae and serum were collected and subjected to micro­computed tomography analysis, confocal laser­scanning microscopic observation, Van Gieson's fuchsin staining, tartrate­resistant acid phosphatase staining and ELISA. Ligatures slightly reduced the alveolar bone mineral density (BMD) and bone formation rate, but significantly reduced alveolar crest height (ACH). Ovariectomy reduced the alveolar BMD, impaired the trabecular structure, reduced the bone formation rate and increased the serum levels of bone resorption markers. Animals in the OVX + ligature group exhibited a lower alveolar BMD, a poorer trabecular structure, a reduced ACH, a lower bone formation rate and higher serum levels of bone resorption markers compared with those in the control group. The results of the present study showed that ovariectomy enhanced alveolar bone loss and reduced the ACH of rats with experimental periodontitis. Thus, post­menopausal osteoporosis may influence the progression of periodontitis.

Sclerostin antibody treatment causes greater alveolar crest height and bone mass in an ovariectomized rat model of localized periodontitis.

INTRODUCTION: Periodontitis and osteoporosis are bone destructive diseases with a high prevalence in the adult population. The concomitant presence of osteoporosis may be a risk factor of progression of periodontal destruction. We studied the effect of sclerostin-neutralizing monoclonal antibody (Scl-Ab) on alveolar bone endpoints in an ovariectomized (OVX) rat model of induced experimental periodontitis. METHODS: Sixty female, 4-month-old Sprague-Dawley rats underwent sham operation or bilateral OVX and were left untreated for 2 months. Experimental periodontitis (ligature) was established by placing silk sutures subgingival to the right maxillary first and second molar teeth for 4 weeks, and feeding the rats food and high-sugar drinking water during this period. Thereafter, ligatures were removed and 25mg/kg vehicle or Scl-Ab was administered subcutaneously twice weekly for 6 weeks. Rats were randomized into four groups: (1) Control (Sham+Vehicle), (2) Sham+Ligature+Vehicle, (3) OVX+Ligature+Vehicle, and (4) OVX + Ligature + Scl-Ab. Terminal blood and right maxilla specimens were collected for analyses. RESULTS: Group 3 rats showed lower bone volume fraction (BVF) of alveolar bone with higher bone resorption and lower bone formation than Group 2 rats. Group 4 rats had higher alveolar crest height, as assessed by linear distance of cementoenamel junction to the alveolar bone crest and greater alveolar bone mass using Micro CT, than Group 3 rats. Significantly higher values of mineral apposition rate (MAR) and mineralizing surface/bone surface (MS/BS) were also observed in Group 4 rats by analyzing polychrome sequential labeling data. Increased serum osteocalcin and osteoprotegerin, and deceased serum tartrate-resistant acid phosphatase and CTx-1 illustrate the ability of Scl-Ab to increase alveolar bone mass by enhancing bone formation and decreasing bone resorption in an animal model of estrogen deficiency osteopenia plus periodontitis. CONCLUSION: Scl-Ab could be a potential bone anabolic agent for improving alveolar crest height and higher alveolar bone mass in conditions where alveolar bone loss in periodontitis is compounded by estrogen deficiency osteopenia.

Simvastatin prevents alveolar bone loss in an experimental rat model of periodontitis after ovariectomy.

BACKGROUND: Periodontitis is an inflammatory disease characterized by the loss of connective tissue and alveolar bone. There is an increasing evidence that periodontitis is associated with a number of chronic disease, including osteoporosis. Periodontitis and osteoporosis are both bone destructive diseases and of high prevalence in adult population. Osteoporosis could increase some inflammatory factors that also participate in the progression of periodontitis, so as to facilitate the alveolar bone resorption. Simvastatin, specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme reductase, is of pleiotropic effects including anti-catabolic and anabolic effect on bone metabolism. This study aimed to explore the local and systemic effect of simvastatin on maxillary in rats with both osteoporosis and periodontitis. METHODS: Thirty-six 4-month-old female Sprague Dawley rats were randomly assigned to six groups: sham group, ligature group, ovariectomized (OVX) + ligature group, local simvastatin administration to OVX + ligature rats (local simvastatin group), oral simvastatin administration to OVX + ligature rats (oral simvastatin group), local and oral simvastatin administration to OVX + ligature rats (L&O simvastatin group). One month after OVX, ligatures were placed on the maxillary first (M1) and second molars (M2) for 4 weeks on all rats except those in the sham group, followed by simvastatin treatment for 2 months. The maxillae, serum, and femurs were collected for further examination including micro-computed (micro-CT) tomography, hematoxylin and eosin (H&E) staining, tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assays (ELISA), and the three-point bending test. RESULTS: Local simvastatin administration increased alveolar crest height and prevented local alveolar bone loss without alteration of systemic bone loss. Oral administration prevented local and systemic bone loss with no effect on alveolar crest height. CONCLUSIONS: Our results indicate that simvastatin has the potential of promoting bone formation and reducing alveolar bone loss in maxillary following ovariectomy (OVX) and ligature placement in rats.

The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway.

The aim of this study was to assess the effect of enoxacin on osteoclastogenesis and titanium particle-induced osteolysis. Wear particles liberated from the surface of prostheses are associated with aseptic prosthetic loosening. It is well established that wear particles induce inflammation, and that extensive osteoclastogenesis plays a critical role in peri-implant osteolysis and subsequent prosthetic loosening. Therefore, inhibiting extensive osteoclast formation and bone resorption could be a potential therapeutic target to prevent prosthetic loosening. In this study, we demonstrated that enoxacin, a fluoroquinolone antibiotic, exerts potent inhibitory effects on titanium particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of mature osteoclasts decreased after treatment with enoxacin in vivo, suggesting that osteoclast formation might be inhibited by enoxacin. We then performed in vitro studies to confirm our hypothesis and revealed the mechanism of action of enoxacin. Enoxacin inhibited osteoclast formation by specifically abrogating RANKL-induced JNK signaling. Collectively, these results suggest that enoxacin, an antibiotic with few side effects that is widely used in clinics, had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.

Smoking, radiotherapy, diabetes and osteoporosis as risk factors for dental implant failure: a meta-analysis.

BACKGROUND: There are conflicting reports as to the association between smoking, radiotherapy, diabetes and osteoporosis and the risk of dental implant failure. We undertook a meta-analysis to evaluate the association between smoking, radiotherapy, diabetes and osteoporosis and the risk of dental implant failure. METHODS: A comprehensive research on MEDLINE and EMBASE, up to January 2013, was conducted to identify potential studies. References of relevant studies were also searched. Screening, data extraction and quality assessment were conducted independently and in duplicate. A random-effects meta-analysis was used to pool estimates of relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 51 studies were identified in this meta-analysis, with more than 40,000 dental implants placed under risk-threatening conditions. The pooled RRs showed a direct association between smoking (n = 33; RR = 1.92; 95% CI, 1.67-2.21) and radiotherapy (n = 16; RR = 2.28; 95% CI, 1.49-3.51) and the risk of dental implant failure, whereas no inverse impact of diabetes (n = 5; RR = 0.90; 95% CI, 0.62-1.32) on the risk of dental implant failure was found. The influence of osteoporosis on the risk of dental implant failure was direct but not significant (n = 4; RR = 1.09; 95% CI, 0.79-1.52). The subgroup analysis indicated no influence of study design, geographical location, length of follow-up, sample size, or mean age of recruited patients. CONCLUSIONS: Smoking and radiotherapy were associated with an increased risk of dental implant failure. The relationship between diabetes and osteoporosis and the risk of implant failure warrant further study.