Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.
In
breast cancer chemophotothermal therapy, it is a great challenge
for the development of multifunctional nanoagents for precision targeting
and the effective treatment of tumors, especially for metastasis.
Herein, we successfully design and synthesize a multifunctional black
phosphorus (BP)-based nanoagent, BP/DTX@PLGA, to address this challenge.
In this composite nanoagent, BP quantum dots (BPQDs) are loaded into
poly(lactic-co-glycolic acid) (PLGA) with additional
conjugation of a chemotherapeutic agent, docetaxel (DTX). The in vivo
distribution results demonstrate that BP/DTX@PLGA shows striking tropism
for targeting both primary tumors and lung metastatic tumors. Moreover,
BP/DTX@PLGA exhibits outstanding controllable chemophotothermal combinatory
therapeutics, which dramatically improves the efficacy of photothermal
tumor ablation when combined with near-light irradiation. Mechanistically,
accelerated DTX release from the nanocomplex upon heating and thermal
treatment per se synergistically incurs apoptosis-dependent cell death,
resulting in the elimination of lung metastasis. Meanwhile, in vitro
and in vivo results further confirm that BP/DTX@PLGA possesses good
biocompatibility. This study provides a promising BP-based multimodal
nanoagent to constrain cancer metastasis.
With the rapid development of nanotechnology and an increasing use of nanoenabled consumer products, there is an urgent need to develop precautionary tools to evaluate acute lung toxicity of engineered nanomaterials (ENMs). As natural pulmonary surfactant (PS) film represents the initial barrier of nano–bio interactions in the lungs, a novel in vitro experimental method, called constrained drop surfactometry (CDS), is developed to quantitatively evaluate PS inhibition caused by ENMs. The results show that at a very low concentration, four representative ENMs, including carbon nanotubes, graphene oxide, zinc oxide, and silver nanoparticles, all increase in vitro minimum surface tension of a modified natural PS, Infasurf. These in vitro results are related to the extensive alveolar collapse and inflammation observed in vivo in mice exposed to these ENMs in an intratracheal instillation model. Thus, there may be a direct correlation between in vitro surface tension increase due to PS inhibition by ENMs and in vivo lung toxicity revealed by alveolar collapse and inflammation. Compared to commonly used animal models, CDS holds great promise for the development of an animal‐free, easy‐to‐use, and low‐cost precautionary assay for the prediction of acute lung toxicity of inhaled ENMs.
During pregnancy, iron requirements are increased to support maternal erythropoietic expansion and fetal growth and development. To meet these requirements, dietary iron absorption increases, and available iron stores are mobilized. These adjustments are thought to be in large part mediated by the iron-regulatory hormone hepcidin, which controls the concentrations of ferroportin, the sole exporter of iron into the extracellular fluid and blood plasma. Hepcidin regulation of iron availability during healthy and abnormal pregnancies is not well understood. In our cross-sectional study, we compared hepcidin, iron and hematological parameters between nonpregnant control women, healthy pregnant women in the first and second trimester, and women with spontaneous abortion in the first trimester. We found that in healthy pregnancy, hepcidin increased in the first trimester compared with nonpregnant women, but then decreased during the second trimester. The second trimester hepcidin levels decreased despite stable serum iron concentrations, suggesting active suppression of hepcidin, presumably to enhance iron availability as iron demand increases. In women with spontaneous abortion during the first trimester, hepcidin, serum iron, and ferritin concentrations were all increased compared with the first trimester healthy pregnancy. Although the specific mechanisms remain to be determined, our findings demonstrate that maternal hepcidin is regulated by signals related to the progression of pregnancy, and that pregnancy loss is associated with profound changes in maternal iron metabolism. These observations highlight the existence of fetoplacental signals that modulate maternal iron homeostasis.
Contaminant-bearing fine biochar particles (FBPs) may exert significantly different toxicity profiles from their contaminant-free counterparts. While the role of FBPs in promoting contaminant uptake has been recognized, it is unclear whether the binding of contaminants can modify the biochemical reactivity and toxicological profiles of FBPs. Here, we show that binding of benzo[a]pyrene (B(a)P, a model polycyclic aromatic hydrocarbon) at environmentally relevant exposure concentrations markedly alters the cytotoxicity of FBPs to macrophages, an important line of innate immune defense against airborne particulate matters (PMs). Specifically, B(a)P-bearing FBPs elicit more severe disruption of the phospholipid membrane, endocytosis, oxidative stress, autophagy, and compromised innate immune defense, as evidenced by blunted proinflammatory effects, compared with B(a)P-free FBPs. Notably, the altered cytotoxicity cannot be attributed to the dissolution of B(a)P from the B(a)P-bearing FBPs, but appears to be related to B(a)P adsorption-induced changes of FBPs bioreactivity toward macrophages. Our findings highlight the significance of environmental chemical transformation in altering the bioreactivity and toxicity of PMs and call for further studies on other types of carbonaceous nanoparticles and additional exposure scenarios.
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