Serum Cytokines and FeNO in School-Aged Children with Mycoplasma pneumoniae Pneumonia.

BACKGROUND Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) that is particularly prevalent in school-aged children. This study explored the potential involvement of cytokines in children with Mycoplasma pneumoniae pneumonia (MPP) infection. MATERIAL AND METHODS Children aged 3-7 years who were hospitalized due to CAP infection were enrolled and divided into 2 groups: an MPP group (n=33) and a NMPP group (n=38), along with 21 age-matched healthy controls. Clinical characteristics and laboratory data were recorded. Serum levels of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were assessed using Luminex xMAP technology. Correlation analysis and ROC curves analysis were also performed to further explore the role of these detected cytokines in CAP. RESULTS Compared with the healthy controls, the serum expression of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were significantly higher in the MPP and NMPP groups. Furthermore, serum IL-18 expression was found to be significantly correlated with lgE, FeNO, IL-5, IL-8, and IL-13 concentrations. Significant differences were also observed between the MPP group and NMPP group patients in levels of IL-18, IL-5, and IL-6, and further ROC analysis showed that the area under the curve (AUC) of IL-18 and IL-5 were 0.813 (95% CI: 0.710-0.917; P<0.01) and 0.844 (95% CI: 0.756-0.933; P<0.01), respectively. CONCLUSIONS IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 serum levels showed significant differences in children with CAP. IL-18 and IL-5 were much higher in the MPP group compared to the NMPP group patients, whereas IL-6 levels were significantly lower in these 2 groups.

Expanding the Chemical Space of Succinate Dehydrogenase Inhibitors via the Carbon-Silicon Switch Strategy.

The carbon-silicon switch strategy has become a key technique for structural optimization of drugs to widen the chemical space, increase drug activity against targeted proteins, and generate novel and patentable lead compounds. Flubeneteram, targeting succinate dehydrogenase (SDH), is a promising fungicide candidate recently developed in China. We describe the synthesis of novel SDH inhibitors with enhanced fungicidal activity to enlarge the chemical space of flubeneteram by employing the C-Si switch strategy. Several of the thus formed flubeneteram-silyl derivatives exhibited improved fungicidal activity against porcine SDH compared with the lead compound flubeneteram and the positive controls. Disease control experiments conducted in a greenhouse showed that trimethyl-silyl-substituted compound W2 showed comparable and even higher fungicidal activities compared to benzovindiflupyr and flubeneteram, respectively, even with a low concentration of 0.19 mg/L for soybean rust control. Furthermore, compound W2 encouragingly performed slightly better control than azoxystrobin and was less active than benzovindiflupyr at the concentration of 100 mg/L against soybean rust in field trials. The computational results showed that the silyl-substituted phenyl moiety in W2 could form strong van der Waals (VDW) interactions with SDH. Our results indicate that the C-Si switch strategy is an effective method for the development of novel SDH inhibitors.

Fangjing decoction relieves febrile seizures-induced hippocampal neuron apoptosis in rats via regulating the Akt/mTOR pathway.

Background: Fangjing decoction is a Traditional Chinese Medicine that exhibits anticonvulsive effects in treating febrile seizures (FS). Its action mechanism and the regulation on Akt/mammalian target of rapamycin (mTOR) pathway were revealed in the present study.Methods: FS model was established in Sprague-Dawley rats with or without Fangjing decoction treatment. On day 5, following initiation of drug treatment, seizures were monitored. Hippocampal neuron apoptosis was assessed using terminal dUTP nick end-labeling method. The levels of Bax, protein kinase B (Akt), phospho-Akt (p-Akt), mTOR, and p-mTOR proteins were analyzed using Western blotting. The content of hippocampal γ-aminobutyric acid (GABA) was measured by using ELISA assay.Results: Compared with the control group (n=8), Fangjing decoction effectively prolonged the latency but shortened the duration of FS in rats (n=8). Concomitantly, the apoptosis of hippocampal neurons, as well as Bax protein levels were also decreased in FS rats which were treated with Fangjing decoction. In addition, the Akt/mTOR signaling was found to be activated in rat hippocampus following FS, as evidenced by increased p-Akt and p-mTOR, while Fangjing decoction could inhibit the activation of Akt/mTOR signaling. Furthermore, the low GABA content in rat hippocampus following FS was significantly elevated by Fangjing decoction treatment. More importantly, SC79, a specific activator for Akt, apparently attenuated the protective effects of Fangjing decoction on FS rats.Conclusion: These results suggest that Fangjing decoction protects the hippocampal neurons from apoptosis by inactivating Akt/mTOR pathway, which may contribute to mitigating FS-induced brain injury.