Geniposide Alleviates Glucocorticoid-Induced Inhibition of Osteogenic Differentiation in MC3T3-E1 Cells by ERK Pathway

Glucocorticoid (GC) therapy is the leading cause of secondary osteoporosis and the therapeutic and preventative drugs for GC-induced osteoporosis are limited. In this study, we investigated the protective effects of geniposide on dexamethasone (DEX)-induced osteogenic inhibition in MC3T3-E1 cells. The results showed that there was no obvious toxicity on MC3T3-E1 cells when geniposide was used at the doses ranging from 1 to 75 μM. In DEX-treated MC3T3-E1 cells, geniposide promoted the alkaline phosphatase (ALP) activity and the mineralization. In addition, geniposide also significantly increased the mRNA and protein expression of osteopontin (OPN), Runt-related transcription factor 2 (Runx2), and Osterix (Osx) in DEX-treated MC3T3-E1 cells. Furthermore, geniposide activated ERK pathway in DEX-treated MC3T3-E1 cells. The ERK activation inhibitor U0126 and glucagon-like peptide-1 (GLP-1) receptor antagonist exendin 9-39 abolished the geniposide-induced activation of ERK and inhibited the protective effect of geniposide. Taken together, our study revealed that geniposide alleviated GC-induced osteogenic suppression in MC3T3-E1 cells. The effect of geniposide was at least partially associated with activating ERK signaling pathway via GLP-1 receptor. Geniposide might be a potential therapeutic agent for GC-induced osteoporosis

Computational design of transmembrane pores.

Transmembrane channels and pores have key roles in fundamental biological processes1 and in biotechnological applications such as DNA nanopore sequencing2-4, resulting in considerable interest in the design of pore-containing proteins. Synthetic amphiphilic peptides have been found to form ion channels5,6, and there have been recent advances in de novo membrane protein design7,8 and in redesigning naturally occurring channel-containing proteins9,10. However, the de novo design of stable, well-defined transmembrane protein pores that are capable of conducting ions selectively or are large enough to enable the passage of small-molecule fluorophores remains an outstanding challenge11,12. Here we report the computational design of protein pores formed by two concentric rings of α-helices that are stable and monodisperse in both their water-soluble and their transmembrane forms. Crystal structures of the water-soluble forms of a 12-helical pore and a 16-helical pore closely match the computational design models. Patch-clamp electrophysiology experiments show that, when expressed in insect cells, the transmembrane form of the 12-helix pore enables the passage of ions across the membrane with high selectivity for potassium over sodium; ion passage is blocked by specific chemical modification at the pore entrance. When incorporated into liposomes using in vitro protein synthesis, the transmembrane form of the 16-helix pore-but not the 12-helix pore-enables the passage of biotinylated Alexa Fluor 488. A cryo-electron microscopy structure of the 16-helix transmembrane pore closely matches the design model. The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer channels and pores for a wide variety of applications

Precisely controlled resorcinol-formaldehyde resin coating for fabricating core-shell, hollow, and yolk-shell carbon nanostructures

MOST of China [2011CB932403, 2009CB930703]; NSFC [21131005, 21021061, 20925103, 20923004]; Fok Ying Tung Education Foundation [121011]This work provides a facile one-step sol-gel route to synthesize high-quality resorcinol-formaldehyde (RF) resin coated nanocomposites that can be further used to fabricate desired carbon nanostructures. Colloidal particles with different morphologies and sizes can be coated with high-quality RF resin shells by the proposed cationic surfactant assisted RF resin coating strategy. The as-synthesized RF resin coated nanocomposites are ideal candidates for selective synthesis of core-shell, hollow, and yolk-shell carbon nanostructures. Based on the carboxylic functional RF resin coating, graphitic carbon nanostructures can also be synthesized by employing the graphitization catalyst. The as-synthesized carbon nanostructures show the advantageous performances in several applications. Hollow carbon spheres are potential electrode materials for lithium-sulfur batteries. Hollow graphitic spheres are promising catalyst supports for oxygen reduction reaction. And yolk-shell structured Au@HCS nanoreactors with ultrathin shells exhibit high catalytic activity and recyclability in confined catalysis

Microorganism-mediated synthesis of chemically difficult-to-synthesize Au nanohorns with excellent optical properties in the presence of hexadecyltrimethylammonium chloride

Fundamental Research Funds for Central Universities [2010121051]; NSFC [21106117, 21036004]Closely packed, size-controllable and stable Au nanohorns (AuNHs) that are difficult to synthesize through pure chemical reduction are facilely synthesized using a microorganism-mediated method in the presence of hexadecyltrimethylammonium chloride (CTAC). The results showed that the size of the as-synthesized AuNHs could be tuned by adjusting the dosage of the Pichia pastoris cells (PPCs). The initial concentrations of CTAC, ascorbic acid (AA) and tetrachloroaurate trihydrate (HAuCl4 center dot 3H(2)O) significantly affected the formation of the AuNHs. Increasing the diameters of AuNHs led to a red shift of the absorbance bands around 700 nm in their UV-vis-NIR spectra. Interestingly, the AuNH/PPC composites exhibited excellent Raman enhancement such that rhodamine 6G with concentration as low as (10(-9) M) could be effectively detected. The formation process of the AuNHs involved the initial binding of the Au ions onto the PPCs with subsequent reduction by AA to form supported Au nanoparticles (AuNPs) based on preferential nucleation and initial anisotropic growth on the platform of the PPCs. The anisotropic growth of these AuNPs, which was influenced by CTAC and PPCs, resulted in the formation of growing AuNHs, while the secondary nucleation beyond the PPCs produced small AuNPs that were subsequently consumed through Ostwald ripening during the aging of the AuNHs. This work exemplifies the fabrication of novel gold nanostructures and stable bio-Au nanocomposites with excellent optical properties by combining microorganisms and a surfactant

Efficacy and Safety of the Injection of the Traditional Chinese Medicine Puerarin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis of 53 Randomized Controlled Trials

Objective. The injection of the traditional Chinese patent medicine puerarin has been widely used in the treatment of various diseases such as angina pectoris or ischemic stroke. We aim to evaluate the efficacy and safety of puerarin injection for the treatment of diabetic peripheral neuropathy (DPN). Methods. A systematic literature search was performed in seven medical databases from their inception until June 2017. 53 studies with RCTs, totaling 3284 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager 5.3 software. Results. The meta-analysis showed that puerarin injection for the treatment of DPN was significantly better compared with the control group in terms of the total effective rate. The result showed that puerarin injection for the treatment of DPN can significantly increase the probability of sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of the median and peroneal nerves. Conclusions. This meta-analysis demonstrated that puerarin injection may be more effective and safe for the treatment of DPN. However, further and higher quality RCTs are required to prove its efficacy and provide meaningful evidence for clinical treatment due to the poor methodological quality

miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4

Glucocorticoid administration is the leading cause of secondary osteoporosis. In this study, we tested the hypotheses that histone deacetylase 4 (HDAC4) is associated with glucocorticoid-induced bone loss and that HDAC4 dependent bone loss can be ameliorated by miRNA-365. Our previous studies showed that miR-365 mediates mechanical stimulation of chondrocyte proliferation and differentiation by targeting HDAC4. However, it is not clear whether miR-365 has an effect on glucocorticoid-induced osteoporosis. We have shown that, in MC3T3-E1 osteoblasts, dexamethasone (DEX) treatment decreased the expression of miR-365, which is accompanied by the decrease of cell viability in a dose-dependent manner. Transfection of miR-365 ameliorated DEX-induced inhibition of MC3T3-E1 cell viability and alkaline phosphatase activity, and attenuated the suppressive effect of DEX on runt-related transcription factor 2 (Runx2), osteopontin (OPN), and collagen 1a1 (Col1a1) osteogenic gene expression. In addition, miR-365 decreased the expression of HDAC4 mRNA and protein by direct targeting the 3′-untranslated regions (3′-UTR) of HDAC4 mRNA in osteoblasts. MiR-365 increased Runx2 expression and such stimulatory effect could be reversed by HDAC4 over-expression in osteoblasts. Collectively, our findings indicate that miR-365 ameliorates DEX-induced suppression of cell viability and osteogenesis by regulating the expression of HDAC4 in osteoblasts, suggesting miR-365 might be a novel therapeutic agent for treatment of glucocorticoid-induced osteoporosis

Identification and analysis of CYP450 genes from transcriptome of Lonicera japonica and expression analysis of chlorogenic acid biosynthesis related CYP450s

Background Lonicera japonica is an important medicinal plant that has been widely used in traditional Chinese medicine for thousands of years. The pharmacological activities of L. japonica are mainly due to its rich natural active ingredients, most of which are secondary metabolites. CYP450s are a large, complex, and widespread superfamily of proteins that participate in many endogenous and exogenous metabolic reactions, especially secondary metabolism. Here, we identified CYP450s in L. japonica transcriptome and analyzed CYP450s that may be involved in chlorogenic acid (CGA) biosynthesis. Methods The recent availability of L. japonica transcriptome provided opportunity to identify CYP450s in this herb. BLAST based method and HMM based method were used to identify CYP450s in L. japonica transcriptome. Then, phylogenetic analysis, conserved motifs analysis, GO annotation, and KEGG annotation analyses were conducted to characterize the identified CYP450s. qRT-PCR was used to explore expression patterns of five CGA biosynthesis related CYP450s. Results In this study, 151 putative CYP450s with complete cytochrome P450 domain, which belonged to 10 clans, 45 families and 76 subfamilies, were identified in L. japonica transcriptome. Phylogenetic analysis classified these CYP450s into two major branches, A-type (47%) and non-A type (53%). Both types of CYP450s had conserved motifs in L. japonica. The differences of typical motif sequences between A-type and non-A type CYP450s in L. japonica were similar with other plants. GO classification indicated that non-A type CYP450s participated in more molecular functions and biological processes than A-type. KEGG pathway annotation totally assigned 47 CYP450s to 25 KEGG pathways. From these data, we cloned two LjC3Hs (CYP98A subfamily) and three LjC4Hs (CYP73A subfamily) that may be involved in biosynthesis of CGA, the major ingredient for pharmacological activities of L. japonica. qRT-PCR results indicated that two LjC3Hs exhibited oppositing expression patterns during the flower development and LjC3H2 exhibited a similar expression pattern with CGA concentration measured by HPLC. The expression patterns of three LjC4Hs were quite different and the expression pattern of LjC4H3 was quite similar with that of LjC3H1. Discussion Our results provide a comprehensive identification and characterization of CYP450s in L. japonica. Five CGA biosynthesis related CYP450s were cloned and their expression patterns were explored. The different expression patterns of two LjC3Hs and three LjC4Hs may be due to functional divergence of both substrate and catalytic specificity during plant evolution. The co-expression pattern of LjC3H1 and LjC4H3 strongly suggested that they were under coordinated regulation by the same transcription factors due to same cis elements in their promoters. In conclusion, this study provides insight into CYP450s and will effectively facilitate the research of biosynthesis of CGA in L. japonica

Autologous Stem Cell Therapy in Critical Limb Ischemia: A Meta-Analysis of Randomized Controlled Trials

Objective. Critical limb ischemia (CLI) is the most dangerous stage of peripheral artery disease (PAD). Many basic researches and clinical treatment had been focused on stem cell transplantation for CLI. This systematic review was performed to review evidence for safety and efficacy of autologous stem cell therapy in CLI. Methods. A systematic literature search was performed in the SinoMed, PubMed, Embase, ClinicalTrials.gov, and Cochrane Controlled Trials Register databases from building database to January 2018. Results. Meta-analysis showed that cell therapy significantly increased the probability of ulcer healing (RR = 1.73, 95% CI = 1.45–2.06), angiogenesis (RR = 5.91, 95% CI = 2.49–14.02), and reduced the amputation rates (RR = 0.59, 95% CI = 0.46–0.76). Ankle-brachial index (ABI) (MD = 0.13, 95% CI = 0.11–0.15), TcO2 (MD = 12.22, 95% CI = 5.03–19.41), and pain-free walking distance (MD = 144.84, 95% CI = 53.03–236.66) were significantly better in the cell therapy group than in the control group (P<0.01). Conclusions. The results of this meta-analysis indicate that autologous stem cell therapy is safe and effective in CLI. However, higher quality and larger RCTs are required for further investigation to support clinical application of stem cell transplantation

Autologous Stem Cell Therapy in Critical Limb Ischemia: A Meta-Analysis of Randomized Controlled Trials

Objective. Critical limb ischemia (CLI) is the most dangerous stage of peripheral artery disease (PAD). Many basic researches and clinical treatment had been focused on stem cell transplantation for CLI. This systematic review was performed to review evidence for safety and efficacy of autologous stem cell therapy in CLI. Methods. A systematic literature search was performed in the SinoMed, PubMed, Embase, ClinicalTrials.gov, and Cochrane Controlled Trials Register databases from building database to January 2018. Results. Meta-analysis showed that cell therapy significantly increased the probability of ulcer healing (RR = 1.73, 95% CI = 1.45–2.06), angiogenesis (RR = 5.91, 95% CI = 2.49–14.02), and reduced the amputation rates (RR = 0.59, 95% CI = 0.46–0.76). Ankle-brachial index (ABI) (MD = 0.13, 95% CI = 0.11–0.15), TcO2 (MD = 12.22, 95% CI = 5.03–19.41), and pain-free walking distance (MD = 144.84, 95% CI = 53.03–236.66) were significantly better in the cell therapy group than in the control group (P<0.01). Conclusions. The results of this meta-analysis indicate that autologous stem cell therapy is safe and effective in CLI. However, higher quality and larger RCTs are required for further investigation to support clinical application of stem cell transplantation

University Academic Performance Development Prediction Based on TDA

With the rapid development of higher education, the evaluation of the academic growth potential of universities has received extensive attention from scholars and educational administrators. Although the number of papers on university academic evaluation is increasing, few scholars have conducted research on the changing trend of university academic performance. Because traditional statistical methods and deep learning techniques have proven to be incapable of handling short time series data well, this paper proposes to adopt topological data analysis (TDA) to extract specified features from short time series data and then construct the model for the prediction of trend of university academic performance. The performance of the proposed method is evaluated by experiments on a real-world university academic performance dataset. By comparing the prediction results given by the Markov chain as well as SVM on the original data and TDA statistics, respectively, we demonstrate that the data generated by TDA methods can help construct very discriminative models and have a great advantage over the traditional models. In addition, this paper gives the prediction results as a reference, which provides a new perspective for the development evaluation of the academic performance of colleges and universities