Sodium Para-aminosalicylic Acid Inhibits Lead-Induced Neuroinflammation in Brain Cortex of Rats by Modulating SIRT1/HMGB1/NF-κB Pathway.

Lead (Pb) is considered to be a major environmental pollutant and occupational health hazard worldwide which may lead to neuroinflammation. However, an effective treatment for Pb-induced neuroinflammation remains elusive. The aim of this study was to investigate the mechanisms of Pb-induced neuroinflammation, and the therapeutic effect of sodium para-aminosalicylic acid (PAS-Na, a non-steroidal anti-inflammatory drug) in rat cerebral cortex. The results indicated that Pb exposure induced pathological damage in cerebral cortex, accompanied by increased levels of inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). Moreover, Pb decreased the expression of silencing information regulator 2 related enzyme 1 (SIRT1) and brain-derived neurotrophic factor (BDNF), and increased the levels of high mobile group box 1 (HMGB1) expression and p65 nuclear factor-κB (NF-κB) phosphorylation. PAS-Na treatment ameliorated Pb-induced histopathological changes in rat cerebral cortex. Moreover, PAS-Na reduced the Pb-induced increase of TNF-α and IL-1ß levels concomitant with a significant increase in SIRT1 and BDNF levels, and a decrease in HMGB1 and the phosphorylation of p65 NF-κB expression. Thus, PAS-Na may exert anti-inflammatory effects by mediating the SIRT1/HMGB1/NF-κB pathway and BDNF expression. In conclusion, in this novel study PAS-Na was shown to possess an anti-inflammatory effect on cortical neuroinflammation, establishing its efficacy as a potential treatment for Pb exposures.

Supramolecular Fluorescent Probes for the Detection of Reactive Oxygen Species Discovered via High-Throughput Screening.

Supramolecular fluorescent probes for the detection of reactive oxygen species (ROSs) are designed based on a pro-guest strategy. Nine commercially available fluorescent dyes, six host molecules, and a pro-guest are used to rapidly generate a library of 54 potential supramolecular probes. These potential supramolecular probes are screened in a high-throughput fashion using a plate reader to discover seven "hits" or workable probes. The mechanism is confirmed to be ROS-induced conversion from a low-binding-affinity pro-guest to a high-binding-affinity guest and the competitive displacement of the encapsulated fluorescent dye. The response to H2O2 of four supramolecular probes is found to be concentration-dependent and may be used for quantitative analysis of H2O2. The supramolecular probe is selectively responsive toward other oxidative agents, such as NaClO and Na2SO3. The cell study shows that supramolecular probes are capable of detecting H2O2 in human cancer cells (MCF-7 or HeLa).

Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-ß1/Smad and Akt/mTOR pathways.

Traumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms. For in vitro studies, lung fibroblasts (IMR-90 cells), with/without PLB treatment or TGF-ß1 induction, were used. The viability and proliferation of IMR-90 cells were examined by CCK-8 and EdU incorporation assays. The differentiation of IMR-90 cells was assessed by detecting the mRNA and protein expression levels of collagen (COL)-1 and alpha-smooth muscle actin (α-SMA). Besides, immunofluorescence assay was conducted to evaluate the localization of α-SMA in TGF-ß1-induced IMR-90 cells. Moreover, the combination of PLB with/without TßRI (SB-431,542), PI3K/Akt (Ly294002) or mTOR (rapamycin) inhibitor was pretreated on IMR-90 cells after TGF-ß1 induction. For in vivo studies, a rat model of TS was established. The pathological features and severity of TS were determined by hematoxylin and eosin staining. The protein levels of TGF-ß1/Smad and Akt/mTOR pathways were detected for both in vitro and in vivo models. PLB effectively inhibited the proliferation and differentiation of TGF-ß1-induced IMR-90 cells, and suppressed TGF-ß1/Smad and Akt/mTOR signaling pathways both in vivo and in vitro. Furthermore, PLB reduced the degree of TS in rats. Taken together, our results indicate that PLB regulates lung fibroblast activity and attenuates TS in rats by inhibiting TGF-ß1/Smad and Akt/mTOR signaling pathways. In conclusion, this study implies that PLB may serve as a promising therapeutic compound for TS.

Pro-guest and acyclic cucurbit[n]uril conjugated polymers for the controlled release of anti-tumor drugs.

We report "pro-guest" and acyclic cucurbit[n]uril conjugated polymers as supramolecular drug delivery systems (DDSs). These supramolecular DDSs could encapsulate anti-tumor drugs. Under acidic conditions, an acid-labile "pro-guest" degraded to become a "competing guest", which displaced and released the encapsulated drug at a tunable rate.