Owing to their unique chemical and physical properties, hydrogels are attracting increasing attention in both basic and translational biomedical studies. Although the classical hydrogels with static ...networks have been widely reported for decades, a growing number of recent studies have shown that structurally dynamic hydrogels can better mimic the dynamics and functions of natural extracellular matrix (ECM) in soft tissues. These synthetic materials with defined compositions can recapitulate key chemical and biophysical properties of living tissues, providing an important means to understanding the mechanisms by which cells sense and remodel their surrounding microenvironments. This review begins with the overall expectation and design principles of dynamic hydrogels. We then highlight recent progress in the fabrication strategies of dynamic hydrogels including both degradation-dependent and degradation-independent approaches, followed by their unique properties and use in biomedical applications such as regenerative medicine, drug delivery, and 3D culture. Finally, challenges and emerging trends in the development and application of dynamic hydrogels are discussed.
The microenvironment is increasingly recognized to have key roles in cancer, and biomaterials provide a means to engineer microenvironments both in vitro and in vivo to study and manipulate cancer. ...In vitro cancer models using 3D matrices recapitulate key elements of the tumour microenvironment and have revealed new aspects of cancer biology. Cancer vaccines based on some of the same biomaterials have, in parallel, allowed for the engineering of durable prophylactic and therapeutic anticancer activity in preclinical studies, and some of these vaccines have moved to clinical trials. The impact of biomaterials engineering on cancer treatment is expected to further increase in importance in the years to come.
The purpose of the present study was to evaluate the effectiveness of probiotics on type II diabetes mellitus (T2DM).
We performed a comprehensive search on PubMed, Web of Science, China National ...Knowledge Infrastructure, Chinese Scientific Journal Databases, Wan Fang database and China biology medicine disc for relevant studies published before June 2019. Glycated hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR) and fasting blood glucose (FBG) were used as indicators for T2DM. Inverse-variance weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for the mean HbA1c, FBG and HOMA-IR changes from baseline.
15 randomized controlled trials (RCT) with a total of 902 participants were included into the meta-analysis. Considering the clinical heterogeneity caused by variation of dosage and duration of probiotic treatment, random-effects model was used to estimate the pooled WMD. Significantly greater reduction in HbA1c% (WMD = - 0.24, 95% CI - 0.44, - 0.04, p = 0.02), FBG (WMD = - 0.44 mmol/L, 95% CI - 0.74, - 0.15, p = 0.003) and HOMA-IR (WMD = - 1.07, 95% CI - 1.58, - 0.56, p < 0.00001) were observed in probiotics treated group. Further sensitivity analysis verified the reliability and stability of our results.
The results of our meta-analysis indicated that probiotics treatment may reduce HbA1c, FBG and insulin resistance level in T2DM patients. More clinical data and research into the mechanism of probiotics are needed to clarify the role of probiotics in T2DM.
The oxidative state of intestinal tracts of healthy animals were investigated after short-term intake of half-fin anchovy hydrolysates (HAHp) and their thermal or Maillard reaction products (MRPs). ...After one month of continuous oral gavage of HAHp, HAHp-heated products (HAHp-H), the MRPs of HAHp with 3% of glucose (HAHp-3%G MRPs), and the MRPs of HAHp with 3% of fructose (HAHp-3%F MRPs) at a dose of 1.0 g/kg of body weight per day into healthy ICR male mice, the concentrations of serum low-density and high-density lipoprotein cholesterol did not significantly change compared to the control group (CK, gavage with saline). Similar results were found for the interleukin-6 concentrations of all groups. By comparison, HAHp-H, HAHp-3%G MRPs, and HAHp-3%F MRPs administration decreased serum tumor necrosis factor-α concentration as compared to the CK group (
< 0.05). No histological damage was observed in the jejunum, ileum, and colonic tissues of all groups. However, HAHp-H treatment induced higher upregulation of Kelch-like ECH-associated protein 1, transcription factors Nrf-2, associated protective phase-II enzymes of NAD(P)H: quinine oxidoreductase-1, and hemoxygenase-1 in colon tissue, as well as higher upregulation of endogenous antioxidant enzymes, including copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase 2 than other groups (
< 0.05). Additionally, increases in Nε-carboxymethyllysine expression in the colonic tissues of all groups were consistent with their increased oligopeptide transporter 1 expressions. Our results suggest that the thermal products of HAHp might have a broad application prospect in improving antioxidant defense in vivo in healthy animals.
In order to further develop and utilize shrimp processing by-products, in this study, a novel antibacterial hydrolysate of shrimp by-products by pepsin hydrolysis (SPH) was prepared. The ...antibacterial effect of SPH on specific spoilage organisms of squid after end storage at room temperature (SE-SSOs) was investigated. SPH showed an antibacterial effect on the growth of SE-SSOs, with (23.4 ± 0.2) mm of inhibition zone diameter. The cell permeability of SE-SSOs was enhanced after SPH treatment for 12 h. Some bacteria were twisted and shrunk, while pits and pores formed and intracellular contents leaked under scanning electron microscopy observation. The flora diversity of SE-SSOs treated with SPH was determined by a 16S rDNA sequencing technique. Results showed that SE-SSOs were mainly composed of the phyla of Firmicutes and Proteobacteria, among which
(47.29%) and
(38.35%) were dominant genera. SPH treatment resulted in a significant reduction in the relative abundance of the genus
and increased the abundance of
. Linear discriminant analysis (LDA) of LEfSe conveyed that SPH treatment had a significant impact on altering the bacterial structure of SE-SSOs. The 16S PICRUSt of Cluster of Orthologous Group (COG) annotation revealed that SPH treatment for 12 h could significantly increase the function of transcription level K, while SPH treatment for 24 h could downregulate post-translational modifications, protein turnover, and chaperone metabolism functions O. In conclusion, SPH has a proper antibacterial effect on SE-SSOs and can change the flora structure of SE-SSOs. These findings will provide a technical basis for the development of inhibitors of squid SSOs.
We introduce concentration‐dependent number and brightness (cdN&B), a fluorescence fluctuation technique that can be implemented on a standard confocal microscope and can report on the thermodynamics ...of membrane protein association in the native plasma membrane. It uses transient transfection to enable measurements of oligomer size as a function of receptor concentration over a broad range, yielding the association constant. We discuss artifacts in cdN&B that are concentration‐dependent and can distort the oligomerization curves, and we outline procedures that can correct for them. Using cdN&B, we characterize the association of neuropilin 1 (NRP1), a protein that plays a critical role in the development of the embryonic cardiovascular and nervous systems. We show that NRP1 associates into a tetramer in a concentration‐dependent manner, and we quantify the strength of the association. This work demonstrates the utility of cdN&B as a powerful tool in biophysical chemistry.
Concentration‐dependent number and brightness (cdN&B) is a fluorescence fluctuation technique that can be implemented on a standard confocal microscope and report on the thermodynamics of membrane protein association in the native plasma membrane. cdN&B uses transient transfection to enable measurements of oligomer size as a function of receptor concentration over a broad range, yielding the association constant.
Three-dimensional (3D) tissue-engineered models of the blood-brain barrier (BBB) recapitulate in vivo shear stress, cylindrical geometry, and cell-ECM interactions. Here we address four issues ...associated with BBB models: cell source, barrier function, cryopreservation, and matrix stiffness. We reproduce a directed differentiation of brain microvascular endothelial cells (dhBMECs) from two fluorescently labeled human induced pluripotent stem cell lines (hiPSCs) and demonstrate physiological permeability of Lucifer yellow over six days. Microvessels formed from cryopreserved dhBMECs show expression of BBB markers and maintain physiological barrier function comparable to non-cryopreserved cells. Microvessels displaying physiological barrier function are formed in collagen I hydrogels with stiffness matching that of human brain. The dilation response of microvessels was linear with increasing transmural pressure and was dependent on matrix stiffness. Together these results advance capabilities for tissue-engineered BBB models.
Variations in a multitude of material microenvironmental properties have been observed across tissues in vivo, and these have profound effects on cell phenotype. Phenomenological experiments have ...suggested that certain of these features of the physical microenvironment, such as stiffness, could sensitize cells to other features; meanwhile, mechanistic studies have detailed a number of biophysical mechanisms for this sensing. However, the broad molecular consequences of these potentially complex and nonlinear interactions bridging from biophysical sensing to phenotype have not been systematically characterized, limiting the overall understanding and rational deployment of these biophysical cues. Here, we explore these interactions by employing a 3D cell culture system that allows for the independent control of culture substrate stiffness, stress relaxation, and adhesion ligand density to systematically explore the transcriptional programs affected by distinct combinations of biophysical parameters using RNA-seq. In mouse mesenchymal stem cells and human cortical neuron progenitors, we find dramatic coupling among these substrate properties, and that the relative contribution of each property to changes in gene expression varies with cell type. Motivated by the bioinformatic analysis, the stiffness of hydrogels encapsulating mouse mesenchymal stem cells was found to regulate the secretion of a wide range of cytokines, and to accordingly influence hematopoietic stem cell differentiation in a Transwell coculture model. These results give insights into how biophysical features are integrated by cells across distinct tissues and offer strategies to synthetic biologists and bioengineers for designing responses to a cell’s biophysical environment.
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