The brain's vasculature is likely to be subjected to the same age-related physiological and anatomical changes affecting the rest of the cardiovascular system. Since aerobic fitness is known to alleviate both cognitive and volumetric losses in the brain, it is important to investigate some of the possible mechanisms underlying these beneficial changes. Here we investigated the role that estimated cardiorespiratory fitness (eCRF) plays in determining the relationship between aging and cerebral blood flow (CBF) in a group of older adults (ages 55–85). Using arterial spin labeling to quantify CBF, we found that blood flow in the gray matter was positively correlated with eCRF and negatively correlated with age. Subsequent analyses revealed that eCRF fully mediated the effects of age on CBF in the gray matter, but not in the white matter. Additionally, regional measures of CBF were related to regional measures of brain volume. These findings provide evidence that age-related effects on cerebrovascular health and perfusion in older adults are largely influenced by their eCRF levels.

Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell-sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell-cell contact, and diffusion. In this review article we will explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro- and nano- fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, we will review the maturation of micropatterning in 2D, pseudo-3D systems, and patterning within 3D hydrogels in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues.

Background: Stem cell-based therapies have shown great promise in regenerative medicine and continue to generate wide interest in future clinical applications. However, the issue of storage and preservation of stem cells, for future clinical applications, still requires extensive investigation. Objective: The purpose of this study was to evaluate the effect of cryopreservation on the regenerative capacity of bone marrow stem cells in periodontal defects in dogs. Materi als and Methods: Bone marrow mesenchymal stem cells (BMSCs) were obtained from 5 beagle dogs. After cryopreservation for 1 month, cell viability, surface adherence ability, alkaline phosphatase activity and mineralized nodule formation were assessed. Twenty-six periodontal fenestration defects (5 × 5 mm) were created at a location 5 mm apical to the cemento-enamel junction in experimental teeth. Cryopreserved BMSCs were transplanted into the defects using a collagen scaffold carrier. Freshly isolated BMSCs and collagen scaffold alone were used as controls. All animals were sacrificed 8 weeks after surgery, and specimens were evaluated by histomorphometry. Results: Cryopreservation had no discernible negative effect on BMSC growth and differentiation in vitro. Both freshly isolated and cryopreserved BMSC transplantations induced significantly better periodontal regeneration with newly formed cementum, alveolar bone and periodontal ligament compared with the application of collagen scaffold alone. Conclusion: Cryopreserved BMSCs showed no altered regenerative capacity compared with freshly isolated BMSCs in the application of periodontal regeneration.

BackgroundMacrophage inhibitory cytokine 1 (MIC-1/GDF15) has been identified as a potential novel biomarker for detection of pancreatic cancer (PCa). However, the diagnostic value of serum MIC-1 for pancreatic ductal adenocarcinoma (PDAC), particularly for those at the early stage, and the value for treatment response monitoring have not yet been investigated.MethodsMIC-1 expression in tumor tissue was analyzed by RT-PCR from 64 patients with PDAC. Serum MIC-1 levels were detected by ELISA in 1472 participants including PDAC, benign pancreas tumor, chronic pancreatitis and normal controls. The diagnostic performance of MIC-1 was assessed and compared with CA19.9, CEA and CA242, and the value of it as a predictive indicator for therapeutic response and tumor recurrence was also evaluated.ResultsMIC-1 levels were significantly elevated in PDAC tissues as well as serum samples. The sensitivity of serum MIC-1 for PDAC diagnosis was much higher than that of CA19.9 (65.8% vs. 53.3%) with similar specificities. Furthermore, serum MIC-1 detected 238 out of 377 (63.1%) CA19.9-negative PDAC. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA19.9 in distinguishing early-stage PDAC from normal serum with a higher sensitivity (62.5% vs. 25.0% respectively). Notably, serum MIC-1 level was significantly decreased in patients with PDAC after curative resection and returned to elevated levels when tumor relapse occurred.ConclusionsSerum MIC-1 is significantly elevated in most PDAC, including those with negative CA19.9 and early stage disease, and thus may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of PDAC.

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Basigin (BSG) is a multifunctional glycoprotein that plays an important role in male reproduction since male knockout (KO) mice are sterile. The Bsg KO testis lacks elongated spermatids and mature spermatozoa, a phenotype similar to that of alpha-mannosidase IIx (MX) KO mice. MX regulates formation of N-acetylglucosamine (GlcNAc) terminated N-glycans that participate in germ cell-Sertoli cell adhesion. Results showed that Bsg KO spermatocytes displayed normal homologous chromosome synapsis and progression through meiosis. However, only punctate expression of the round spermatid marker SP-10 in the acrosomal granule of germ cells of Bsg KO mice was detected indicating that spermatogenesis in Bsg KO mice was arrested at the early round spermatid stages. We observed a large increase in the number of germ cells undergoing apoptosis in Bsg KO testes. Using lectin blotting, we determined that GlcNAc terminated N-glycans are linked to BSG. GlcNAc terminated N-glycans were significantly reduced in Bsg KO testes. These observations indicate that BSG may act as a germ cell-Sertoli cell attachment molecule. Loss of BSG significantly reduced adhesion between GC-2 and SF7 cells. Moreover, wild type testes showed strong expression of N-cadherin (CDH2) while expression was greatly reduced in the testes of Bsg KO mice. In addition, the integrity of the blood-testis barrier (BTB) was compromised in Bsg KO testes. In conclusion, although some Bsg KO spermatogonia can undergo normal progression to the spermatocyte stage, BSG-mediated germ cell-Sertoli cell interactions appear to be necessary for integrity of the BTB and spermatocyte progression to mature spermatozoa.

Cancer progression involves complex signals within the tumor microenvironment that orchestrate proliferation and invasive processes. The mechanical properties of the extracellular matrix (ECM) within this microenvironment has been demonstrated to influence growth and the migratory phenotype that precedes invasion. Here we present the integration of a label-free quantitative phase imaging technique, spatial light interference microscopy (SLIM)—with protein-conjugated hydrogel substrates—to explore how the stiffness of the ECM influences melanoma cells of varying metastatic potential. Melanoma cells of high metastatic potential demonstrate increased growth and velocity characteristics relative to cells of low metastatic potential. Cell velocity in the highly metastatic population shows a relative insensitivity to matrix stiffness suggesting adoption of migratory routines that are independent of mechanics to facilitate invasion. The use of SLIM and engineered substrates provides a new approach to characterize the invasive properties of live cells as a function of microenvironment parameters. This work provides fundamental insight into the relationship between growth, migration and metastatic potential, and provides a new tool for profiling cancer cells for clinical grading and development of patient-specific therapeutic regimens.

Aim: Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. Methods: Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. Results: A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. Conclusion: Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.