Conjugated linoleic acid prevents age-induced bone loss in mice by regulating both osteoblastogenesis and adipogenesis.

Osteoporosis (OP) can increase the risk of bone fracture and other complications, which is a major clinical problem. Previous researches have revealed that conjugated linoleic acid (CLA) can promote the bone formation. But the mechanisms are not clear. Thus, we tested the hypothesis that CLA acts on bone formation might be via mTOR Complex1 (mTORC 1) pathway by in vitro and vivo assays. We studied the effect of CLA mix on MC3T3-E1 pre-osteoblasts differentiation into osteoblasts, and bone formation under osteoporotic conditions. At the same time, 3T3-L1 pre-adipocyte with the same CLA mix concentration gradient for 8 days with adipogenic differentiation medium. We found that Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) expressions of pre-osteoblasts were up-regulated. Moreover in presence of CLA, peroxisome proliferators-activated receptor γ(PPARγ) and CCAAT/enhancer-binding protein (C/EBPα) were down-regulated. Osteoporosis mice bone parameters in the distal femoral meraphysis were significantly increased compared with placebo mice. Furthermore, the phosphor-S6 (P-S6) was suppressed and phosphor-AKT (P-AKT) was up-regulated. Consistently, CLA can stimulate differentiation of osteoblasts and inhibited pre-adipocytes differentiated into adipocytes via AKT/mTORC1 signal pathway. Overall CLA thus be a suitable candidate for the treatment of patients with postmenopausal osteoporosis and obesity.

Key extracellular proteins and TF-miRNA co-regulatory network in diabetic foot ulcer: Bioinformatics and experimental insights.

BACKGROUND: Diabetic foot ulcers (DFUs), a serious complication of diabetes, are associated with abnormal extracellular protein (EP) metabolism. The identification of key EPs and their regulatory networks is crucial for the understanding of DFU formation and development of effective treatments. In this study, a large-scale bioinformatics analysis was conducted to identify potential therapeutic targets and experimental validation was performed to ensure the reliability and biological relevance of the findings. METHODS: Due to the comprehensive profiling of DFU samples provided by the GSE80178 dataset, we initially selected it to derive differentially expressed genes (DEGs) associated with DFU. Subsequently, utilizing the UniProt database and annotated EP list from the Human Protein Atlas annotation database, we screened for extracellular protein-related differentially expressed genes (EP-DEGs) due to their crucial role in the pathogenesis and healing of DFU. We examined EP-DEG pathway enrichment and protein-protein interaction networks, analyzed paired full-thickness skin tissue samples from 24 patients with DFUs and healthy controls, and performed polymerase chain reaction (PCR) experiments to validate candidate genes. Ultimately, we constructed a transcription factor (TF)-microRNA (miRNA)-hub gene co-regulatory network to explore upstream and downstream regulatory connections based on validated DEGs. RESULTS: Four crucial candidate genes (FMOD, LUM, VCAN, and S100A12) were identified and verified via PCR analysis. The TF-miRNA-hub EP-DEG regulatory network contained the pivotal TFs TRIM28 and STAT3 and the miRNAs hsa-mir-20a-5p, hsa-miR-21, and hsa-miR-203. CONCLUSION: The findings of this study advance our understanding of the pathology of DFU by defining key roles of specific EPs and elucidating a comprehensive regulatory network. These insights pave the way for novel approaches to improve DFU treatment outcomes.

Matrix stiffness regulates epithelial-mesenchymal transition via cytoskeletal remodeling and MRTF-A translocation in osteosarcoma cells.

Matrix stiffness is known to alter cellular behaviors in various biological contexts. Previous investigations have shown that epithelial-mesenchymal transition (EMT) promotes the progression and invasion of tumor. Mechanical signaling is identified as a regulator of EMT. However, the molecular mechanisms underlying the influence exerted by matrix stiffness on EMT in osteosarcoma remains largely unknown. Using polyacrylamide hydrogel model, we investigate the effects of matrix stiffness on EMT and migration in osteosarcoma. Our data indicates that high matrix stiffness regulates cell morphology and promotes EMT and migration in osteosarcoma MG63 cell line in vitro. Notably, matrix stiffness promotes polymerization of actin and nuclear accumulation of myocardin-related transcription factor A (MRTF-A). Furthermore, inhibiting MRTF-A by CCG 203971 significantly reduces EMT and migration on rigid gels. These data suggest that matrix stiffness of the tumor microenvironment actively regulate osteosarcoma EMT and migration through cytoskeletal remodeling and translocation of MRTF-A, which may contribute to cancer progression.

Upregulation of UBAP2L in Bone Marrow Mesenchymal Stem Cells Promotes Functional Recovery in Rats with Spinal Cord Injury.

Post-translational modifications of cellular proteins with ubiquitin or ubiquitin-like proteins regulate many cellular processes, such as cell proliferation, differentiation, apoptosis, signal transduction, intercellular immune recognition, inflammatory response, stress response, and DNA repair. Nice4/UBAP2L is an important member in the family of ubiquitin-like proteins, and its biological function remains unknown. This study aimed to investigate the effect of UBAP2L on spinal cord injury (SCI). At first, rat bone marrow mesenchymal stem cells (BMSCs) were infected with adeno-associated virus to induce over-expression of Nice4. Subsequently, the infected BMSCs were transplanted into rats suffering from semi-sectioned SCI. The results showed that the over-expression of Nice4 significantly promoted the proliferation and differentiation of BMSCs. In addition, the transplantation of infected BMSCs into the injured area of SCI rats improved the function repair of SCI. Importantly, the immunohistochemical and hematoxylin-eosin staining and RT-PCR results showed that the number of neuronal cells, oligodendrocytes, and astrocytes was significantly increased in the injured area, along with significantly upregulated expression of cyclin D1 and p38 mitogen-activated protein kinase (MAPK). Meanwhile, the expression of caspase 3 protein was significantly down-regulated. In conclusion, the over-expression of Nice4 gene can promote the functional recovery in SCI rats by promoting cell proliferation and inhibiting apoptosis. The results of this study indicate an alternative option for the clinical treatment of SCI.

The synergistic effect of bone forming peptide-1 and endothelial progenitor cells to promote vascularization of tissue engineered bone.

Large segmental bone defect repair remains a challenge in orthopedic surgeries. The tissue engineered bone graft will be a promising approach if vascularization of the graft is realized. In this study, beta-tricalcium phosphate (ß-TCP) scaffold incorporated with bone forming peptide-1 (BFP-1) was fabricated. Endothelial progenitor cells (EPCs) were introduced as well. We investigated the effect of BFP-1 on the proliferation, differentiation, and angiogenic functions of EPCs. Additionally, segmental femur bone defect was created in rabbits. Prevascularized ß-TCP scaffold was constructed and implanted into the bone defect. The vascularization and bone formation were evaluated after 4 and 12 weeks. The results showed that BFP-1 promoted the angiogenesis of EPCs through activating the activin receptor-like kinase-1/Smad pathway. The prevascularized tissue engineered bone graft enhanced capillary vessel in-growth and new bone formation. Significantly higher values of vascularization and radiographic grading scores were observed in groups involving EPCs and BFP-1, compared to ß-TCP scaffold alone. In conclusion, the synergy between EPCs and BFP-1 improved the vascularization and new bone regeneration, which has great potentials in clinical applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1008-1021, 2018.

Polymer/reduced graphene oxide functionalized sponges as superabsorbents for oil removal and recovery.

Polyurethane dish-washing (PU-DW) sponges are functionalized sequentially with polyethylenimine (PEI) and graphene oxide (GO) to form PEI/reduced graphene oxide (RGO) PU-DW sponges. The PEI/RGO PU-DW sponge consists of PEI/RGO sheets having numerous pores, with diameters ranging from 236 to 254nm. To further enhance hydrophobicity and absorption capacity of oil, PEI/RGO PU-DW sponge is further coated with 20% phenyltrimethoxysilane (PTMOS). The PTMOS/PEI/RGO PU-DW sponge absorbs various oils within 20s, with maximum absorption capacity values of 880% and 840% for bicycle chain oil and motorcycle engine oil, respectively. The absorbed oils were released completely by squeezing or immersed in hexane. The PTMOS/PEI/RGO PU-DW sponge efficiently separates oil/water mixtures through a flowing system. Having the advantages of faster absorption rate, reusability, and low cost, the PTMOS/PEI/RGO PU-DW sponge holds great potential as a superabsorbent for efficient removal and recovery of oil spills as well as for the separation of oil/water mixtures.

Optical and electrochemical applications of silicon-carbon dots/silicon dioxide nanocomposites.

Various colors of photoluminescent SiC-dots/SiO2 prepared through a simple heating process have been employed for optical and electrochemical applications. Blue (B)-, green (G)-, and tan (T)-SiC-dots/SiO2 powders have been prepared from SiC-dots that had been prepared from 3-aminopropyl trimethoxysilane through a hydrothermal route by simply controlling heating at 60 °C for 60 min and 300 °C for 10 and 20 min, respectively. The B-, G-, and T-SiC-dots/SiO2 nanocomposites emit at 455, 534, and 574 nm, respectively, under excitation at 360 nm. B-, G-, and T-SiC-dots/SiO2 glass films show at least seven colors when excited at 360, 460, and 520 nm. Through a heat-induced photoluminescence (PL) change, a representative lithographic pattern of B-SiC-dots/SiO2 films has been fabricated using a near-infrared laser. The B-, G-, and T-SiC-dots/SiO2 also possess high electrocatalytic activity for the oxygen reduction reaction. Having such interesting PL and electrical properties, the stable, low-toxic, and cost-effective B-, G-, and T-SiC-dots/SiO2 nanocomposites show great economic potential in many applications such as light-emitting diodes, photoluminescent windows, and fuel cells.

Photoluminescent AuCu bimetallic nanoclusters as pH sensors and catalysts.

A facile and one-pot approach to the preparation of gold (Au) and copper (Cu) bimetallic nanoclusters (NCs) is unveiled. AuCu NCs reveal features of orange photoluminescence (PL), reversible pH-dependent PL properties, and efficient catalytic activity for degradation of methylene blue (MB).