Oscillating Fluid Flow Activated Osteocyte Lysate-Based Hydrogel for Regulating Osteoblast/Osteoclast Homeostasis to Enhance Bone Repair.

As major regulators on bone formation/resorption in response to mechanical stimuli, osteocytes have shown great promise for restoring bone injury. However, due to the unmanageable and unabiding cell functions in unloading or diseased environments, the efficacy of osteogenic induction by osteocytes has been enormously limited. Herein, a facile method of oscillating fluid flow (OFF) loading for cell culture is reported, which enables osteocytes to initiate only osteogenesis and not the osteolysis process. After OFF loading, multiple and sufficient soluble mediators are produced in osteocytes, and the collected osteocyte lysates invariably induce robust osteoblastic differentiation and proliferation while restraining osteoclast generation and activity under unloading or pathological conditions. Mechanistic studies confirm that elevated glycolysis and activation of the ERK1/2 and Wnt/ß-catenin pathways are the major contributors to the initiation of osteoinduction functions induced by osteocytes. Moreover, an osteocyte lysate-based hydrogel is designed to establish a stockpile of "active osteocytes" to sustainably deliver bioactive proteins, resulting in accelerated healing through regulation of endogenous osteoblast/osteoclast homeostasis.

In vitro and in vitro toxicity study of diesel exhaust particles using BEAS-2B cell line and the nematode Caenorhabditis elegans as biological models.

It is well accepted that diesel exhaust particles (DEPs) are highly associated with improper function of organ systems. In this study, DEP toxicity was performed by using in vitro human BEAS-2B cell line and in vivo animal model, namely, Caenorhabditis elegans (C. elegans). The potential toxicity of DEP was assessed by the apical endpoints of BEAS-2B cell line and reflections of C. elegans under exposure scenarios of 0~50 µg mL-1 DEP. With the increase of DEP exposure concentration, microscopic accumulations in the cytoplasm of cell line and intestine of C. elegans were observed. Such invasion of DEP impaired the behaviors of C. elegans as well as its un-exposed offspring and caused significant impeded locomotion. Moreover, the disorders of dopaminergic function were observed simultaneously under DEP exposure, specifically manifested by the decreased transcriptional expression of dat-1. The stress responses instructed by the expression of hsp-16.2 were also increased sharply in TJ375 strain of C. elegans at DEP concentrations of 1 and 10 µg mL-1. In the case of cellular reactions to DEP exposure, the injuries of membrane integrity and the decreased viability of cell line were simultaneously identified, and reactive oxygen species (ROS), damaged DNA fragment, and upregulated apoptosis were monotonically elevated in cell lines with the increase of DEP concentrations. This study provided a systematic insight into toxicity of DEP both in vivo and vitro, demonstrating that DEP exposure could disturb the stability of cell system and further threat the stability of organism.

Nonylphenol induced individual and population fluctuation of Caenorhabditis elegans: Disturbances on developmental and reproductive system.

The environmental risks that have arisen from endocrine disruption compounds (EDCs) have become global challenges, especially for persistent bio-accumulated xenobiotic chemicals, such as nonylphenol (NP). In the present study, the population dynamics of Caenorhabditis elegans (C. elegans) were systemically investigated by conducting developmental and reproductive bioassays under the exposure of NP, which has been widely detected in actual aquatic environments. The results revealed that under NP exposure (400 µg L-1 NP), developmental indictors of C. elegans, including the body length and width were significantly inhibited at different life stages of L1 and L4 larva, and the growth curves were further adversely affected. In addition, abnormalities in reproductive systems were also observed under NP exposure. Such abnormalities obeyed a dose-dependent relationship with NP levels, which were closely related to the delayed spawning time and decreased reproductive rates. Moreover, the results from global genome expression analysis for nematodes revealed that the most significant enriched GO terms could be predominantly responsible for the dysregulation of growth and reproductive system. The population's parameters, including age composition and intrinsic growth rate (rm d-1), displayed significant changes, with a suppressed potentiality of population growth. Those data elucidated that NP exhibited a profound impact on the dynamic stability of the population, even with no obvious effect on certain biochemical markers.

Photolysis-Induced Neurotoxicity Enhancement of Chlorpyrifos in Aquatic System: A Case Investigation on Caenorhabditis elegans.

Contamination of the environment by toxic pesticides has become of great concern in agricultural countries. Chlorpyrifos (CP) is among the pesticides most commonly detected in the environment owing to its wide agricultural applications. The aim of this study was to compare potential changes in the toxicity of CP after irradiation. To this end, photolysis of CP was conducted under simulated sunlight, and neurotoxicity assessment was carried out at CP of 20 and 50 µg L-1 and its corresponding irradiated mixture solutions which contain a mixture of identified intermediates using the nematode, Caenorhabditis elegans as a model organism. Photodegradation of 20 µg L-1 CP for 1 h produced no obvious reduction of physiological damage, and more serious effects on animal movement were detected after exposure of the animals to a solution of 50 µg L-1 for 1 h irradiation compared with unirradiated solution. GABAergic and cholinergic neurons were selectively vulnerable to CP exposure, and maximal neuropathological alterations were observed after 1 h irradiation of the CP solutions in coherence with the behavioral impairment. The generation of photoproducts was considered to be responsible for the enhanced disturbance on those biological processes. This work provided useful information on the toxicological assessments of chemicals that were produced during the environmental transformation of pesticides.