Human Mesenchymal Stem Cells Improve Angiogenesis and Bone Formation in Severed Finger Rats through SIRT1/Nrf2 Signaling.

BACKGROUND: This study employed a severed finger rat model to analyze the effects of human mesenchymal stem cells (MSCs) on angiogenesis, inflammatory response, apoptosis, and oxidative stress, to evaluate the possible mechanism of the repair effect of MSCs on severed finger (SF) rats. METHODS: Sixty Sprague-Dawley (SD) rats were categorized into five groups (n = 12). The pathological changes of severed finger tissues were investigated by Hematoxylin and eosin (H&E) staining on day 14 after the rats were sacrificed. The levels of inflammatory factors and oxidative stress factors were detected by ELISA. Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick End Labeling (TUNEL) was employed to assess the apoptosis of chondrocytes in severed finger tissues. The expression of osteocalcin (OCN), osteopontin (OPN), Collagen I (Col-1), and CD31 were detected by immunohistochemistry or immunofluorescence assay, respectively. The expression levels of related proteins were determined by western blot. RESULT: Our study presented evidence that MSCs treatment improved pathological changes of skin and bone tissue, diminished the inflammatory response, prevented oxidative stress injury, suppressed chondrocyte apoptosis, and promoted angiogenesis, and bone formation compared to the model group. In addition, EX527 treatment attenuated the effect of MSCs, SRT1720 and ML385 co-treatment also attenuated the effect of MSCs. Importantly, the MSCs treatment increased the expression of Sirtuin 1(SIRT1)/Nuclear factor erythroid2-related factor 2(Nrf2) relate proteins. CONCLUSION: Our study indicated that the mechanism of the effect of MSCs on a severed finger was related to the SIRT1/ Nrf2 signaling pathway.

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.

A biocatalytic peptidobiosensing molecular bridge for detecting osteosarcoma marker protein.

A biosensing scheme requiring only one-step sample incubation before signal collection, and using a compact "three-in-one" probe of target-binding, signal conversion, and amplification, may greatly simplify the design of biosensors. Therefore, sparing the multi-step addition of enzymes, protein, and nanomaterial, as well as the associated complexity and non-specific interactions. In this work, a peptide probe aimed at such compact features has been designed, based on protein-triggered, conformation-driven, and Cu (II) facilitated side-chain di-tyrosine cyclization. This design can use target-probe recognition to induce discriminated cross-linking and self-cleavage of the probe, resulting in retention or dissociation of a signal amplification motif from the search and consequently quantitative detection performance. The method has also been tested preliminarily in fractioned osteosarcoma clinical samples, showing an acceptable coherence between signal readout and clinical diagnosis. On the basis of these early findings, it is reasonable to assume that the proposed probe will be beneficial for the next development of tumor screening and prognosis sensors.

Effect of Naringin on Monosodium Iodoacetate-Induced Osteoarthritis Pain in Rats.

BACKGROUND The aim of the current study was to evaluate the anti-osteoarthritic and anti-inflammatory effect of naringin in a monosodium iodoacetate (MIA)- induced osteoarthritis (OA) model in rats. The anti-osteoarthritic potential of naringin was evaluated against the MIA-induced OA rat model. MATERIAL AND METHODS Wistar rats were used for the study and were divided into the following groups: normal control (saline-treated); group II (MIA-treated): group III (MIA+Naringin), and group IV (MIA+Indomethacin). The potential effect of naringin was evaluated via its effect on the level of proinflammatory cytokines, measuring the weight-bearing distribution, and histopathological analysis. RESULTS The anti-inflammatory effect of naringin was assessed in vitro in lipopolysaccharide-induced RAW 264.6 cells. The results suggest that naringin exerts an anti-inflammatory effect via reducing the production of the prostaglandin E2 (PGE2), nitric oxide (NO), interlukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced RAW cells. Additionally, naringin also supported the recovery of hind-limb weight-bearing, reduced the generation or production of inflammatory mediator and proinflammatory cytokines, and protected the tissue from the damage in the OA model. CONCLUSIONS Naringin appears to be an effective therapeutic drug for the treatment of the OA and OA-related symptoms.

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.

Identification of common mechanisms between endometriosis and ovarian cancer.

PURPOSE: To determine common molecular markers between endometriosis and ovarian cancer. METHODS: Patients included women who underwent laparoscopic excision of ovarian endometriotic lesions (n = 7), healthy non-pregnant women with normal pelvises, who underwent excision of normal peritoneum (n = 7). Two epithelial ovarian cancer (EOC) cell lines were also utilized. Expression of transforming growth factor (TGF)-ß1, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF), estrogen receptor (ER)-1α, progesterone receptor (PR), androgen receptor (AR), and aromatase was evaluated by real-time RT-PCR. RESULTS: Endometriosis and EOC cells manifested significantly higher mRNA levels of TGF-ß1, COX-2, VEGF, ER-1α, AR, and aromatase, while they expressed significantly lower mRNA levels of PR. CONCLUSIONS: Increased TGF-ß1, COX-2, VEGF, ER-1α, AR, and aromatase and decreased PR in endometriotic as well as EOC cells suggests a potential association between these two disease processes. This association is important, as it may reveal common mechanisms for both diseases.