Hu'po Anshen decoction promotes fracture healing in mice with traumatic brain injury through BMP2-COX2-ATF4 signaling pathway.

Hu'po Anshen decoction (HPASD), a traditional Chinese medicine used to treat concussion and fracture, could regulate the expression of bone morphogenetic protein 2 (BMP2). However, whether HPASD affects the fracture healing of traumatic brain injury (TBI) combined with a fracture through BMP2 and its downstream signals remains obscure. The chondrocyte-specific BMP2 conditional knockout mice and chondrocyte-specific cyclooxygenase-2 (COX2) overexpression mice were generated. BMP2 conditional knockout mice were treated with fracture surgery, fracture combined with TBI, or fracture combined with TBI followed by different doses of HPASD (2.4, 4.8, and 9.6 g/kg), respectively. TBI was induced by Feeney's weight-drop technique. The fracture callus formation and fracture sites were determined by X-ray, micro-CT, and histological analyses. The expressions of chondrocyte-, osteoblast-, and BMP2/COX2 signal-related targets were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot assays. The specific absence of BMP2 in chondrocytes led to the prolonged formation of cartilage callus, a delay in the osteogenesis initiation and the downregulation of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, ATF4. Overexpression of COX2 partially reverses the effects of chondrocyte-specific BMP2 knockout mice. HPASD promoted cartilage callus formation and osteogenesis initiation, as accompanied by upregulated expression levels of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, and ATF4 in a time-dependent and concentration-dependent manner in chondrocyte-specific BMP2 knockout mice. Overall, our findings demonstrated that HPASD induced COX2 transcription through the BMP2-Smad1/5/9-RUNX2 axis, and then affected fracture healing through the COX2-mediated EP4-ERK1/2-RSK2-ATF4 axis.

TYRO protein tyrosine kinase-binding protein predicts favorable overall survival in osteosarcoma and correlates with antitumor immunity.

To explore the prognostic significance and underlying mechanism of TYRO protein tyrosine kinase-binding protein (TYROBP) in osteosarcoma. Firstly, the expression of TYROBP was analyzed using the t test. The Kaplan-Meier plotter analysis and a receiver operating characteristic curve were performed to evaluate the influence of TYROBP on overall survival (OS). Further, Cox regression analysis was conducted to predict the independent prognostic factors for OS of osteosarcoma patients, and a nomogram was constructed. Then, the relationship between TYROBP and clinicopathological characteristics was determined using statistical methods. Enrichment analyses were conducted to evaluate the biological functions of TYROBP. Finally, the ESTIMATE algorithm was used to assess the association of TYROBP with immune cell infiltration. TYROBP was significantly increased in osteosarcoma (all P < .001). However, the high expression of TYROBP was related to better OS in osteosarcoma patients. Cox regression analysis showed that TYROBP was an independent prognostic factor for predicting OS (P = .005), especially in patients of the male sex, age <18 years, metastasis, and tumor site leg/foot (all P < .05). Besides, TYROBP mRNA expression was significantly associated with the tumor site (P < .01) but had no remarkable relationship with age, gender, and metastasis status (all P > .05). Functional annotation and gene set enrichment analysis (GSEA) revealed that TYROBP was mainly involved in immune-related pathways. Importantly, TYROBP positively correlated with immune scores (P < .001, R = .87). TYROBP served as an independent prognostic biomarker for OS in osteosarcoma. High TYROBP expression might prolong the survival of osteosarcoma patients mainly through promoting antitumor immunity.

Persistent luminescence-polypyrrole nanocomposite for dual-modal imaging and photothermal therapy of mammary cancer.

Multifunctional nanocomposites that possess imaging and high-performance therapeutic features are experiencing a surge in interest in the precision clinical anticancer treatment. In this work, we reported the fabrication and bio-application of a novel persistent luminescence-polypyrrole nanocomposite (LPLNP@SPP) for photoacoustic/persistent luminescence (PA/PL) dual-modal imaging guided photothermal therapy (PTT). The construction of LPLNP@SPP avoids the PL quenching of LPLNP-OH by the polypyrrole-coating, and thus enables the combination of PL and PTT. The LPLNP@SPP shows excellent biocompatibility, long lasting near-infrared (NIR) PL emitting without in situ excitation and high-contrast PA signals. Meanwhile, this nanocomposite exhibits strong NIR absorbance and exceptional photothermal conversion capability, which provides notable potential for imaging-guided antitumor therapy. Thus, our work highlights the dual-functional core-shell LPLNP@SPP as a feasible theranostic nanoplatform for cancer diagnosis and therapy.

Database Study on the Expression and Purification of Membrane Proteins.

Membrane proteins are crucial for biological processes, and many of them are important to drug targets. Understanding the three-dimensional structures of membrane proteins are essential to evaluate their bio-function and drug design. High-purity membrane proteins are important for structural determination. Membrane proteins have low yields and are difficult to purify because they tend to aggregate. We summarized membrane protein expression systems, vectors, tags, and detergents, which have deposited in the Protein Data Bank (PDB) in recent four-and-a-half years. Escherichia coli is the most expression system for membrane proteins, and HEK293 cells are the most commonly cell lines for human membrane protein expression. The most frequently vectors are pFastBac1 for alpha-helical membrane proteins, pET28a for beta-barrel membrane proteins, and pTRC99a for monotopic membrane proteins. The most used tag for membrane proteins is the 6×His-tag. FLAG commonly used for alpha-helical membrane proteins, Strep and GST for beta- barrel and monotopic membrane proteins, respectively. The detergents and their concentrations used for alpha-helical, beta-barrel, and monotopic membrane proteins are different, and DDM is commonly used for membrane protein purification. It can guide the expression and purification of membrane proteins, thus contributing to their structure and bio function studying.

Recent Advances of Persistent Luminescence Nanoparticles in Bioapplications.

Persistent luminescence phosphors are a novel group of promising luminescent materials with afterglow properties after the stoppage of excitation. In the past decade, persistent luminescence nanoparticles (PLNPs) with intriguing optical properties have attracted a wide range of attention in various areas. Especially in recent years, the development and applications in biomedical fields have been widely explored. Owing to the efficient elimination of the autofluorescence interferences from biotissues and the ultra-long near-infrared afterglow emission, many researches have focused on the manipulation of PLNPs in biosensing, cell tracking, bioimaging and cancer therapy. These achievements stimulated the growing interest in designing new types of PLNPs with desired superior characteristics and multiple functions. In this review, we summarize the works on synthesis methods, bioapplications, biomembrane modification and biosafety of PLNPs and highlight the recent advances in biosensing, imaging and imaging-guided therapy. We further discuss the new types of PLNPs as a newly emerged class of functional biomaterials for multiple applications. Finally, the remaining problems and challenges are discussed with suggestions and prospects for potential future directions in the biomedical applications.

Naringin protects against steroid­induced avascular necrosis of the femoral head through upregulation of PPARγ and activation of the Notch signaling pathway.

Naringin, a flavonoid, is the effective pharmaceutical ingredient of drynaria, with the effects of healing fractures, strengthening bones and promoting kidney function. The aim of the present study was to investigate the potential effect of naringin on steroid­induced avascular necrosis of the femoral head (SANFH). Treatment with naringin markedly protected against the steroid­induced decrease in serum osteocalcin levels, and the rate of osteonecrosis in a model of SANFH. In addition, naringin decreased the total cholesterol and low density lipoprotein/high density lipoprotein ratio in the SANFH rabbit. It was observed that naringin markedly inhibited caspase­3 activity, increased runt­related transcription factor 2 and transcription factor sp7 mRNA expression, promoted alkaline phosphatase activity and upregulated collagen I, peroxisome proliferator­activated receptor (PPAR) Î³2, neurogenic locus notch homolog protein (Notch), ß­catenin and phosphorylated­Rac­α serine/threonine protein kinase protein expression in the SANFH rabbit. The results of the present study demonstrated that naringin protects against SANFH through upregulation of PPARγ2 and activation of the Notch signaling pathway, and may be a useful addition to the treatment options for diseases of the femoral head.

[Larix gmelinii tree-ring width chronology and its responses to climate change in Kuduer, Great Xing' an Mountains].

Based on the established tree-ring width chronology of Larix gmelinii in Kuduer, Great Xing' an Mountains, this paper analyzed the relationships between L. gmelinii tree-ring width chronology and related climatic variables, including air temperature, precipitation, and PDSI. In the study area, the L. gmelinii tree-ring width chronology was significantly negatively correlated with the air temperature in May and July (P<0.01), had no significant correlation with precipitation, but significantly positively correlated with the PDSI in June-August (P<0.05), suggesting that hydro-thermal variables had significant coupling effects to the radial growth of L. gmelinii in its growth season, particularly in May and July. The L. gmelinii tree-ring width chronology had significant correlations with large scale climatic regimes such as the Pacific Decadal Oscillation (PDO) in both low and high frequency variations, illustrating the significant effects of the remote oceanic climatic regimes to the local tree growth.

[Three-tunnels core decompression with implantation of bone marrow stromal cells (bMSCs) and decalcified bone matrix (DBM) for the treatment of early femoral head necrosis].

OBJECTIVE: To analyse retrospectively 3-tunnels core decompression with implantation of bone marrow stromal cells(bMSCs) and decalcified bone matrix (DBM) for treatment of femoral head necrosis in early stages, and to study its therapeutic results and indications. METHODS: According to the University of Pennsyvania system of classification and staging,to treat the patients with 3-tunnels core decompression with implantation of bone marrow stromal cells (bMSCs) and decalcified bone matrix (DBM) for treatment of early femoral head necrosis. Among the total 87 patients (103 hips), the male was 71 (86 hips) and the female 16 (17 hips) with the average age of 47 years old. The average course of disease was 1.3 year. The effect was evaluated by the clinical symptoms, the Harris' scores and the manifestations of radiology before and after operation. RESULTS: All the patients were followed up more than 2 years (average 26 months). The average Harris' scores increased from preoperation 47.3 to postoperation 74.0. The average rate of excellent and good results was 75.7%. The rate of excellent and good was 88% (22/25) in type I, 78.7% (37/47) in type II and 61.3% (19/31) in type III. No severe complications were observed. CONCLUSION: Three-tunnels core decompression with implantation of bMSCs and DBM not only removal the focus of disease, but also use DBM the induction of bone and autologous hone marrow stem cells to differentiate the functions of the femoral head can be resumed loading structure, eliminate pain,improve joint function. It is an effective method for early femoral head necrosis.