BMP-7 modified exosomes derived from synovial mesenchymal stem cells attenuate osteoarthritis by M2 polarization of macrophages.

Background: Although the exosomes derived from mesenchymal stem cells (MSCs) display a therapeutic effect on inflammatory diseases, its application on OA has great limitations due to lack of specificity and targeting. The current study aimed to elucidate the potential therapeutic role of bone morphogenetic proteins-7(BMP-7) modified synovial mesenchymal stem cells-derived exosomes (SMSCs-exo) on OA and mechanism. Methods: For in vitro experiments, LPS-treated macrophages RAW264.7 were treated with SMSCs-exo (exo) or BMP-7 modified SMSCs-exos (BMP-7-exo). The levels of inflammatory factors were assessed by ELISA. Also, the proportion of iNOS and CD206 positive cells were quantified by flow cytometry. Chondrocytes and RAW264.7 were co-culture to evaluate the effects of macrophage polarization on chondrocytes cellular behaviors. This effect on KOA was verified by an experiment in vivo. HE staining and Safranin fast green staining were used to observe the damage of articular cartilage. Immunohistochemistry was used to determine the expression of collagen II and aggrecan in articular cartilage, as well as the expression of iNOS and CD206 in synovial tissues. Results: Our in vitro results showed that BMP-7-exo treatment promoted LPS-induced proliferation of macrophages and chondrocytes, and showed a better ability to reduce inflammation by promoting macrophages M2 polarization. After co-culture with LPS treated macrophages, the proliferation rate and migration of chondrocytes were significantly decreased, while the apoptosis was significantly increased. The macrophages treated with BMP-7-exo and exo partially reversed these changes. The chondrocytes in BMP-7-exo group had higher proliferation rate and migration, as well as lower apoptosis compared with the exo group. Also, the in vivo results showed BMP-7-exo treatment improved the pathological changes of KOA and promoted synovial macrophages M2 polarization. Conclusions: Our results demonstrated that BMP-7-exo attenuated KOA inflammation and cartilage injury by synovial macrophages M2 polarization, suggesting that BMP-7-exo carry much therapeutic potential for OA.

C-reactive protein to albumin ratio (CAR) in predicting surgical site infection (SSI) following instrumented posterior lumbar interbody fusion (PLIF).

Identification of novel markers would contribute to the individualised risk assessment and development of a risk prediction model. This study aimed to investigate the role of the C-reactive protein to albumin ratio (CAR) in predicting surgical site infection (SSI) following instrumented posterior lumbar interbody fusion (PLIF) of lumbar degenerative diseases. This study enrolled patients who underwent PLIF and instrumentation for treatment of lumbar degenerative diseases between 2015 and 2020. Electronic medical records were inquired for data collection, with follow-up register for identifying SSI cases. The optimal cut-off for CAR was determined by constructing the receiver operator characteristic (ROC) curve. Patients with high- or low-CAR value were compared using the univariate analyses, and the association between CAR and the risk of SSI was investigated using multivariate logistics regression analysis. A total of 905 patients were enrolled, twenty-nine (3.2%) had developed an SSI with 72.4% occurring during index hospitalisation, and 11 (1.2%) had deep and 18 (2.0%) superficial SSIs. An SSI was associated with additional 10.7 days of index total hospital stay (P = .001). The CAR was 0-5.43 (median, 0.05), and the optimal cut-off was 0.09 and area under the curve was 0.720 (P < .001). 336 (37.1%) patients had a CAR ≥0.09 and 22 (6.5%) developed an SSI, with a crude risk of 5.6 relative to those with a low CAR. The multivariate analyses showed CAR ≥0.09 was associated with 8.06-fold increased risk of SSI, together with diabetes (P = .018), while hypertension was identified as a protective factor (OR, 0.34; 95%CI, 0.11-1.00, P = .049). High CAR is found to significantly predict the incident SSI following instrumented PLIF of lumbar degenerative diseases, and can be considered as a useful index in practice only after it is verified by future high-level evidences.

GPBAR1 is associated with asynchronous bone metastasis and poor prognosis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death in China. Asynchronous metastasis is the main reason for HCC recurrence, but the current assessment of HCC metastasis and prognosis is far from clinically satisfactory. Materials: In our study, we investigated the expression of G-protein-coupled bile acid receptor (GPBAR1) in HCC tissues and tumor-adjacent tissues by qRT-PCR and immunohistochemistry. The associations between GPBAR1 expression, clinicopathological factors, and asynchronous metastases were assessed by the Chi-square test. The overall survival curves of different variables were plotted with the Kaplan-Meier method, and the statistical significance between different subgroups was analyzed with the log-rank test. The independent prognostic factors were identified by the Cox regression hazard model. Results: GPBAR1 was more highly expressed in HCC tissues than in tumor-adjacent tissues. GPBAR1 expression in HCC was significantly higher than that in liver cirrhosis, followed by normal liver tissues. GPBAR1 was significantly associated with poor prognosis in HCC and can be regarded as an independent prognostic biomarker. Interestingly, GPBAR1 expression in HCC was significantly correlated with asynchronous metastasis to the bone but not to the liver or lung. Conclusions: GPBAR1 was found to be an independent, unfavorable prognostic factor of HCC, as well as an indicator of asynchronous bone metastasis but not liver or lung metastases. Our results could provide a new aspect for HCC metastasis studies and help identify high-risk HCC patients, which helps ameliorate the prognostic assessment of HCC.

Robust inverse-design of scattering spectrum in core-shell structure using modified denoising autoencoder neural network.

Neural network-based inverse design of nanophotonic device network is computationally and time efficient, but in general suffers the problems of robustness and stability against variation of the input target electromagnetic response. The inverse design network is required to be robust against the input electromagnetic response and to be capable of approximating the given electromagnetic response, even under the circumstances that the exact target response may not exist. We introduce a modified denoising autoencoder network to ensure the robustness of neural network-based inverse design, which consists of (1) a pre-trained network as a substitute of numerical simulation and (2) an inverse design network. We further purposely train the network with certain random disturbances added to the training dataset generated by the pre-trained network. Consequently, our modified denoising autoencoder network is more robust and more accurate than the conventional fully connected neural network. The strength and flexibility of our proposed network is illustrated via three concrete examples of achieving the desired scattering spectra of layered spherical scatterers.

Haplotype analysis on relationship of ERCC2 and ERCC3 gene polymorphisms with osteosarcoma risk in Chinese young population.

The purpose of the study was to investigate the association of single-nucleotide polymorphisms (SNPs) within excision repair cross-complementation (ERCC) gene polymorphisms, additional gene-gene interaction, and haplotype combination with osteosarcoma risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs. Logistic regression was performed to investigate the association between six SNPs within ERCC gene, additional gene-gene interaction on osteosarcoma risk. Haplotype analysis was performed using SNPstats ( http://bioinfo.iconcologia.net/SNPstats ). Osteosarcoma risk was significantly higher in carriers with the T allele of ERCC2-rs1799793 than those with GG genotype (GT+ TT vs. GG), adjusted OR (95% CI) = 1.56 (1.13-2.01), and higher in carriers with the A allele of ERCC3-rs4150441 than those with GG genotype (GA+ AA vs. GG), adjusted OR (95% CI) = 1.63 (1.25-2.09). GMDR model indicated a significant two-locus model (p = 0.0107) involving rs1799793 and rs4150441; cross-validation consistency of the two-locus model was 9/10; and the testing accuracy was 60.11%. Participants rs1799793-GT or -TT and rs4150441-GA or -AA genotype have the highest osteosarcoma risk, compared to subjects with rs1799793-GG and rs4150441-GG genotype, OR (95% CI) = 2.87 (1.21-4.63), after covariates adjustment. Haplotype containing the rs1799793-T and rs11615-T alleles was associated with a statistically increased osteosarcoma risk, OR (95% CI) = 1.47 (1.12-1.92). We found that the T allele of ERCC2-rs1799793 and the A allele of ERCC3-rs4150441, interaction between rs1799793 and rs4150441, and haplotype containing the rs1799793T and rs11615-T alleles were all associated with increased osteosarcoma risk.

Fractionation of 50kGy electron beam irradiation: effects on biomechanics of human flexor digitorum superficialis tendons treated with ascorbate.

The electron beam (Ebeam) irradiation has begun to be considered as an efficient alternative to gamma irradiation in the sterilization of allografts in the reconstruction of anterior cruciate ligament. The purpose of this study was to evaluate the biomechanical properties of human tendons after exposure to electron beam and free radical scavenger ascorbate. Forty human flexor digitorum superficialis tendons were prepared from five fresh cadavers and divided randomly into four groups: A, fresh (0kGy); B, 50kGy Ebeam irradiation; C, fractionated 50kGy Ebeam irradiation; D, fractionated 50kGy Ebeam on ascorbate-treated tendons. The fractionation of 50kGy was achieved by repeated irradiation of 2.5kGy for 20 repetitions. Biomechanical properties were analyzed during load-to-failure testing. The fresh tendons were found to be significant different in ultimate load, ultimate elongation relative to tendons in group B. Statistical differences were found between group B and C in ultimate load. No differences were detected between group A and C in all the parameters. Compare tendons in group C and D, significant differences were found in ultimate load and ultimate stress. It is recommended that fractionated 50kGy electron beam irradiation and free radical scavenger ascorbate should be applied in the sterilization of allografts tendons.