Development of chitosan/gelatin hydrogels incorporation of biphasic calcium phosphate nanoparticles for bone tissue engineering

Abstract

The chitosan/gelatin hydrogel incorporated with biphasic calcium phosphate nanoparticles (BCP-NPs) as scaffold (CGB) for bone tissue engineering was reported in this article. Such nanocomposite hydrogels were fabricated by using cycled freeze-thawing method, of which physicochemical and biological properties were regulated by adjusting the weight ratio of chitosan/gelatin/BCP-NPs. The needle-like BCP-NPs were dispersed into composites uniformly, and physically cross-linked with chitosan and gelatin, which were identified via Scanning Electron Microscope (SEM) images and Fourier Transform Infrared Spectroscopy (FT-IR) analysis. The porosity, equilibrium swelling ratio, and compressive strength of CGB scaffolds were mainly influenced by the BCP-NPs concentration. In vitro degradation analysis in simulated body fluids (SBF) displayed that CGB scaffolds were degraded up to at least 30?wt% in one month. Also, CCK-8 analysis confirmed that the prepared scaffolds had a good cytocompatibility through in culturing with bone marrow mesenchymal stem cells (BMSCs). Finally, In vivo animal experiments revealed that new bone tissue was observed inside the scaffolds, and gradually increased with increasing months, when implanted CGB scaffolds into large necrotic lesions of rabbit femoral head. The above results suggested that prepared CGB nanocomposites had the potential to be applied in bone tissue engineering.     

Enhanced functional DNA biosensor for distance-based read-by-eye quantification of various analytes based on starch-hydrolysis-adjusted wettability change in paper devices

Low-cost, equipment-free and quantitative detection of a wide range of analytes of interest at home and in the field holds the potential to revolutionize disease diagnosis, environmental pollution monitoring, and food safety analysis. Herein, we describe a functional DNA biosensor for the first time that integrates analyte-directed assembly of enzyme-coated microbead probes for robust yet efficient signal amplification with a simple quantitative detection motif of distance measurement on portable paper devices based on starch-hydrolysis-adjusted wettability change of paper. Its utility is well demonstrated with highly sensitive and specific detection of model analytes ranging from adenosine (an important small biomolecule; 1.6 μM detection limit) to interferon-γ (a protein marker; 0.3 nM detection limit) and Pb²⁺ (a highly toxic metal ion; 0.5 nM detection limit) by simply using an inexpensive, ubiquitous ruler. The developed general method with the distance-measuring readout should be easily tailored for the portable, read-by-eye, quantitative detection of many other types of analytical targets by taking advantage of their specific functional DNA partners like aptamers and DNAzymes.

A functional DNA sensor was initially developed for the distance-measuring quantification of various analytes based on the starch-hydrolysis-adjusted wettability change of paper.     

Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients

Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l^-1 vs 0.4 ± 0.4 IU l⁻¹, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l⁻¹ vs 1.9 ± 1.1 IU l⁻¹, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.     

Multiple Genes of the Renin-Angiotensin System Are Novel Targets of Wnt/β-Catenin Signaling

Activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because of compensatory upregulation of renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary to achieve greater efficacy. By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and β-catenin induced the binding of LEF-1 to these sites in kidney tubular cells. Overexpression of either β-catenin or different Wnt ligands induced the expression of all RAS genes. Conversely, a small-molecule β-catenin inhibitor ICG-001 abolished RAS induction. In a mouse model of nephropathy induced by adriamycin, either transient therapy or late administration of ICG-001 abolished established proteinuria and kidney lesions. ICG-001 inhibited renal expression of multiple RAS genes in vivo and abolished the expression of other Wnt/β-catenin target genes. Moreover, ICG-001 therapy restored expression of nephrin, podocin, and Wilms’ tumor 1, attenuated interstitial myofibroblast activation, repressed matrix expression, and inhibited renal inflammation and fibrosis. Collectively, these studies identify all RAS genes as novel downstream targets of Wnt/β-catenin. Our results indicate that blockade of Wnt/β-catenin signaling can simultaneously repress multiple RAS genes, thereby leading to the reversal of established proteinuria and kidney injury.     

Suppressor of cytokine signaling 3 A+930-->G (rs4969168) polymorphism is associated with apolipoprotein A1 and low-density lipoprotein cholesterol

This study aimed to detect the association of the suppressor of cytokine signaling 3 gene (SOCS3) A+930-->G (rs4969168) single nucleotide polymorphism (SNP) and environmental factors with serum lipid levels in the Han and Mulao populations. Genotyping of the SOCS3 A+930-->G (rs4969168) SNP was performed in 752 of Han and 690 of Mulao participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype and allele frequencies were significantly different between the Han and Mulao populations (GG, 57.71% vs. 51.16%, GA, 36.97% vs. 41.16%, AA, 5.32% vs. 7.68%, P = 0.023; G, 76.20% vs. 71.74%, A, 23.80% vs. 28.26%; P = 0.006; respectively). Serum apolipoprotein (Apo) A1 levels in Han were different among the genotypes (P < 0.05). Subgroup analyses showed that the levels of ApoA1 in Han females, and ApoA1 and low-density lipoprotein cholesterol (LDL-C) in Mulao males were different among the genotypes (P < 0.05). Serum lipid parameters were also associated with several environmental factors in both ethnic groups (P < 0.05-0.001). These findings suggest that there may be a racial/ethnic- and/or sex-specific association between the SOCS3 A+930-->G (rs4969168) SNP and serum lipid parameters in some populations.     

口腔贱金属合金修复体的生物相容性试验

贱金属合金烤瓷熔附金属修复体是口腔临床修复体应用的主体,存在着较高的不安全性,其生物相容性评价主要有细胞毒性试验、动物试验和临床前试验.细胞毒性检测主要有中性红试验、51Cr释放法、分子滤过试验、甲噻唑四唑氮比色试验、细胞计数试剂盒8试验、乳酸脱氢酶试验、红细胞溶血试验和流式细胞计数等,使用最广泛的细胞是L929细胞和海拉细胞.按细胞接触方式的不同,毒性试验细胞的培养分为浸提液培养法、直接接触法和间接接触法.动物试验可从整体上评价生物相容性,可产生免疫或补体激活反应,但试验难以控制,费用高,费时.动物试验可弥补细胞毒性试验难以模拟的综合反应,因此其与细胞毒性试验一样都是口腔材料生物相容性评价必不可少的环节.