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Abstract The herbicide acetochlor is used in most parts of the world and is frequently detected in agricultural land and surface water; however, knowledge on the neurotoxicity of acetochlor is limited. Here, to test the effects of acetochlor on zebrafish development and behaviour, zebrafish embryos were exposed to acetochlor from 6 h post-fertilization (hpf) to 24 hpf, and larvae at 6 days post-fertilization (dpf) were exposed to acetochlor for 24 h. Both were exposed to 5, 10, or 20 mg/L acetochlor. We found that acetochlor induced developmental abnormalities, locomotion variations and changes in the physiology and gene expression in the embryos and larvae. The abnormalities included spinal curvature, brain abnormalities, and the decreased formation of newborn neurons. Larval locomotion was decreased with increases in the absolute turn angle and sinuosity. Acetylcholinesterase activity reduced in both embryos and larvae, and the expression of genes that are involved in neurodevelopment and the neurotransmitter system altered. Acetochlor increased the production of ROS and the accumulation of MDA but decreased CAT activity in the embryonic brain. Additionally, acetochlor induced cell death in the brain and tail spinal cord, and the expression of the apoptosis-related genes Bcl2 and caspase 3 were significantly upregulated. Collectively, this is the first study to examine the molecular and physiological effects of acetochlor on neuronal development, and the potential mechanisms appear to be associated with oxidative stress and decreased AChE activity, which disrupt the expression of nervous system genes and apoptosis-related genes and finally lead to apoptosis and morphological malformations. Highlights • Acetochlor led to brain abnormalities of zebrafish embryos. • Acetochlor influenced the locomotor behaviour of zebrafish larvae. • Acetochlor induced ROS and apoptosis in the brain of zebrafish embryos. • Acetochlor induced neurotoxicity in early development stages of zebrafish. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most common extracranial solid tumor that affects developing nerve cells in the fetus, infants, and children. miR-124 is a microRNA (miRNA) enriched in neuronal tissues, and VAMP3 (vesicle-associated membrane protein 3) has been reported to be an miR-124 target, although the relationship between NB and miR-124 or VAMP3 is unknown. Our current work identified that miR-124 levels are high in NB cases and that elevated miR-124 correlates with worse NB outcomes. Conversely, depressed VAMP3 correlates with worse NB outcomes. To investigate the mechanisms by which miR-124 and VAMP3 regulate NB, we altered miR-124 or VAMP3 expression in human NB cells and observed that increased miR-124 and reduced VAMP3 stimulated cell proliferation and suppressed apoptosis, while increased VAMP3 had the opposite effects. Genome-wide mRNA expression analyses identified gene and pathway changes which might explain the NB cell phenotypes. Together, our studies suggest that miR-124 and VAMP3 could be potential new markers of NB and targets of NB treatments. [ABSTRACT FROM AUTHOR]

Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. [ABSTRACT FROM AUTHOR]

Temporomandibular joint osteoarthritis (TMJ OA) is an important subtype of temporomandibular disorders (TMD). Articular cartilage destruction is considered a common pathological feature of TMJ OA, which is reported to be mainly induced by chondrocyte apoptosis. Synovial sterile inflammation is an initial factor of TMJ OA-associated articular cartilage destruction. Therefore, determining the mechanism of synovial membrane inflammation-induced articular cartilage destruction in TMJ OA is important for the TMJ OA therapy. In this study, we detected the function of synoviocytes in chondrocyte apoptosis under lipopolysaccharide (LPS)-induced inflammatory conditions and explored the underlying mechanism. We found that synoviocytes in inflammatory conditions facilitated LPS-induced chondrocytes apoptosis by secreting increased Tumor Necrosis Factor α (TNF-α), which was induced by long non-coding RNA plasmacytoma variant translocation 1 (PVT1) upregulation. PVT1 served as a competing endogenous RNA that sponged the microRNA miR-211-3p and prevented the inhibition of TNF-α expression. In conclusion, our in vitro study revealed that PVT1 has a previously unknown role in chondrocyte apoptosis, which may also be a mechanism underlying synoviocyte involvement in TMJ OA. • LPS-stimulated synoviocytes aggravate chondrocytes apoptosis. • PVT1 participates in synoviocytes cells-aggravated chondrocytes apoptosis. • PVT1 upregulates TNF-α through sponging miR-211-3p. [ABSTRACT FROM AUTHOR]

Abstract: Caesalpinia sappan has been shown to have interesting immunosuppressive properties. Its heartwood has long been used in Chinese medicines for treating a variety of immune-mediated pathology and inflammatory disease. The purpose of this work was to evaluate the immunocompetence effects of brazilein on mice lymphocytes in vitro and in vivo. The results showed that brazilein and Caesalpinia sappan ethanol extract (SME) could distinctly inhibit the proliferation of T lymphocyte stimulated by Concanavalin A (Con A) and the proliferation of B lymphocyte stimulated by lipopolysaccharides (LPS), and brazilein could suppress mice humoral immune response by plaque forming cell (PFC) test. In addition, immune organs (thymus and spleen) in mice treated with brazilein were notably atrophied and weight loss in vivo (intraperitoneal injection, i.p.). In attempting to investigate the mechanisms of the immunosuppressive activity of brazilein, we discovered that brazilein can induce apoptosis in mice spleen lymphocytes by flow cytometry analysis and DNA fragmentation assay, which may be one of the pathways that brazilein inhibited immunocompetence of mice lymphocytes. [Copyright &y& Elsevier]

Temperature is a critical abiotic factor in aquaculture farming. Serum cortisol, glucose, respiratory frequency, hepatic glycogen, anti-oxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GPx]), malondialdehyde (MDA) content, and expression of heat shock proteins (hsp70 , 90) and apoptosis-related genes (p53 , caspase3 , bax , bcl2) of turbot were determined at 27 °C under different thermal durations (0, 6, 12, 24, 48, 72, 96 h) to illustrate the underlying physiological response mechanisms. Results showed that cortisol and glucose significantly increased at 27 °C from 0 h to 12 h, and then dramatically decreased from 24 h to 96 h. Respiratory frequency manifested similar results to cortisol. Hepatic glycogen content, GPx and CAT activities gradually decreased in a time-dependent manner under thermal stress. However, SOD activity significantly increased at 6, 12, 24 h and then decreased until the end of thermal stress. Hepatic MDA content significantly increased from 12 h to 96 h. In addition, the apoptosis rate of hepatocyte gradually increased under thermal stress. p53 , caspase3 and bcl2 mRNAs were significantly up-regulated under thermal stress within 6 h, and down-regulated from 12 h to 96 h. bax mRNA was significantly up-regulated from 0 h to 6 h, and no significant difference was observed from 6 h to 96 h. Hepatic hsp70 and hsp90 mRNAs were significantly up-regulated from 6 h to 12 h, which was similar to those of serum glucose results. These results indicate that hyperthermal stress elevates respiratory frequency, serum cortisol and glucose contents, promotes hepatic glycogenolysis, impairs hepatic antioxidant capacity and induces hepatocyte apoptosis by p53 - bax - bcl2 and the caspase-dependent pathways. These findings expand the current knowledge on thermal tolerance and aid the management of turbot in captivity. • Hyperthermal stress affect respiratory frequency, serum cortisol and glucose levels. • Hyperthermal stress promote hepatic glycogenolysis in a time-dependent manner. • Hepatic antioxidant enzyme activities were modulated during hyperthermal stress. • p53 - bax - bcl2 and caspase-dependent pathways involved in hepatocyte apoptosis. • The transcription of hsp70 and hsp90 were modulated subject to hyperthermal stress. [ABSTRACT FROM AUTHOR]