The Differential Metabolic Profiles Between Deltamethrin-Resistant and -Susceptible Strains of Aedes albopictus (Diptera: Culicidae) by 1H-NMR.

Metabolomics can indicate the physiological and biochemical responses of mosquitoes to different stimulants, including insecticides, which allow them to adapt to different inhospitable environments. Though metabolic differences between insecticide-resistant and -susceptible strains have been established for other mosquito species, such as Anopheles and Culex, it is yet to be done for Aedes albopictus (Skuse). In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis performed on Ae. albopictus deltamethrin-resistant and -susceptible strains showed significant differences in amino acid, organic acid, and sugar metabolism. Concentrations of neutral amino acids and sugars tended to be lower in the deltamethrin-resistant strain than in the deltamethrin-suceptible strain, but the concentration of basic and acidic amino acids and organic acids increased. All these changes might accommodate biochemical and physiological needs in deltamethrin-resistant mosquitoes, such as enzyme synthesis and detoxification. This was further confirmed by the predictable draft metabolic map. This is the first report using NMR spectroscopy to investigate the metabolic differences between deltamethrin-resistant and -susceptible strains of Ae. albopictus. To a certain degree, this demonstrates how Ae. albopictus develop insecticide resistance by metabolic reprograming to survive under the insecticide pressure.

MicroRNA miR-155-5p knockdown attenuates Angiostrongylus cantonensis-induced eosinophilic meningitis by downregulating MMP9 and TSLP proteins.

Angiostrongylus cantonensis infection is a major cause of eosinophilic meningitis (EM). Severe cases or cases that involve infants and children present poor prognoses. MicroRNAs (miRNAs), which are important regulators of gene expression in many biological processes, were recently found to be regulators of the host response to infection by parasites; however, their roles in brain inflammation caused by A. cantonensis are still unclear. The current study confirmed that miR-155-5p peaked at 21 days after A. cantonensis infection, and its expression was positively correlated with the concentration of excretory and secretory products (ESPs). We found that miR-155-5p knockdown lentivirus successfully ameliorated brain injury and downregulated the expression of major basic protein (MBP) in vivo, and the number of eosinophils in CSF (and the percentage of eosinophils in peripheral blood were also decreased in the miR-155-5p knockdown group. Moreover, the expression of several eosinophilic inflammation cytokines such as CCL6/C10, ICAM-1, and MMP9, declined after the miR-155-5p knockdown. SOCS1 protein, which is an important negative regulator of inflammation activation, was identified as a direct miR-155-5p target. We further detected the effect of miR-155-5p knockdown on phosphorylated-STAT3 and phosphorylated-p65 proteins, which were found to be negatively regulated by SOCS1 and play an important role in regulating the inflammatory response. We found that miR-155-5p knockdown decreased the activity of p-STAT3 and p-p65, thereby leading to lower expression of MMP9 and TSLP proteins, which were closely related to the chemotaxis and infiltration of eosinophils. Interestingly, the inhibition of p-STAT3 or p-p65 was found to induce the downregulation of miR-155-5p in an opposite manner. These observations suggest that a positive feedback loop was formed between miR-155-5p, STAT3, and NF-κB in A. cantonensis infection and that miR-155-5p inhibition might provide a novel strategy to attenuate eosinophilic meningitis.

Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway.

Since incurable castration-resistant prostate cancer (CRPC) inevitably develops following treatment with androgen deprivation therapy, there is an urgent need to devise new therapeutic strategies to treat this cancer. Pyrimethamine, an FDA-approved antimalarial drug, is known to exert an antitumor activity in various types of human cancer cells. However, whether pyrimethamine can inhibit prostate cancer is not well established. Hence, the present study aimed to characterize the mechanism of action of pyrimethamine on prostate cancer. We investigated the potential effect of pyrimethamine on cell proliferation, cell cycle, and apoptosis in metastatic DU145 and PC3 prostate cancer cells. We found that pyrimethamine inhibited cell proliferation, induced cell cycle arrest in the S phase, and promoted cell apoptosis of prostate cells in vitro; it also suppressed tumor growth in xenograft models. In addition, we observed that pyrimethamine suppressed prostate cancer growth by inhibiting the p38-NF-κB axis in vitro and in vivo. Thus, this study demonstrates that pyrimethamine is a novel p38 inhibitor that can exert antiproliferative and proapoptotic effects in prostate cancer by affecting cell cycle and intrinsic apoptotic signaling, thereby providing a novel strategy for using pyrimethamine in CRPC treatment.

Casticin Attenuates Osteoarthritis-Related Cartilage Degeneration by Inhibiting the ROS-Mediated NF-κB Signaling Pathway in vitro and in vivo.

Casticin, a flavonoid isolated from Vitex trifolia, has been shown to have anti-inflammatory and antitumor effects in previous studies. Osteoarthritis (OA) is a disease based on degenerative pathological changes. The disease process is often accompanied by inflammatory pathological changes. However, there is no safe and effective drug for prevention and treatment. In the present study, we aimed to clarify the role of casticin in the murine model of destabilization of the medial meniscus (DMM). Male BALB/c mice were randomly divided into three groups: Sham, DMM-induced OA treated with vehicle, and DMM-induced OA treated with casticin. Our results indicated that the casticin treatments markedly reduced the destruction of cartilage and OARSI grades compared with those of the vehicle-treated mice. The levels of matrix metalloproteinase-13 (MMP13) in cartilage were also significantly reduced in the casticin-treated mice. Casticin also significantly regulated oxidative stress and reduced inflammation in the cartilage of mice with OA. These results suggest that casticin prevents the development of posttraumatic OA in mice. Consequently, decreased reactive oxygen species levels and suppressed proinflammatory cytokine production were confirmed in casticin-treated IL-1ß-stimulated ADTC5 cells. After casticin treatment, the NF-κB signaling pathway was significantly inhibited in the cells. It can be concluded that casticin can alleviate arthritis-related cartilage degeneration by inhibiting ROS-mediated NF-κB signaling pathway in vitro and in vivo.

Highly improved, non-localized field enhancement enabled by hybrid plasmon of crescent resonator/graphene in infrared wavelength.

The development of surface enhanced infrared absorption has been constrained by the limited field enhancement and narrow-band resonance of commonly used metal resonators. In this theoretical work, the design of a crescent resonator (CR) combined with graphene-enabled plasmon tuning is proposed to settle the drawbacks. The CR is similar to a split ring resonator (SRR), but exhibits a much improved field enhancement. The influence of graphene on the field enhancement of the CR has been systematically investigated. Coupling from localized plasmon of CR to propagating plasmon of graphene has been observed, and the constructive interference of the plasmon wave has led to not only better enhancement inside the gap but also usable enhancements all over the graphene film, which go beyond the localized nature of metal plasmons.

A multifunctional fluorescent aptamer probe for highly sensitive and selective detection of cadmium(II).

We report a highly sensitive and selective strategy for Cd(II) assay using a singly labeled multifunctional probe consisting of a Cd(II)-specific aptamer (CAP), which acted as a recognition element for Cd(II) and a signal reporter. The presence of Cd(II) can induce the conformational switching of the CAP, accompanied by a change in fluorescence intensity. Thereby, a fluorescence strategy for Cd(II) assay was established. The proposed method has a detection limit of 2.15 nM, which is much lower than the detection limits reported in related literature. This strategy involves only an aptamer probe, and the use of such a G4-based quencher avoids the dual labeling of the CAP with fluorophore/quencher units. It is obviously more convenient and economical than the other aptamer-based biosensors for Cd(II) detection. The mechanism by which Cd(II) induces the CAP to change from a random coil sequence to a stem-loop structure was studied in a series of control experiments. This strategy would be helpful in the design of a sensitive analytical platform for various target assays in environmental and biomedical fields. Graphical Abstract The presence of Cd2+ leads to the conformational change of CAP from a random coil sequence to a stem-loop structure, resulting in a quenching in the fluorescence.

Gold nanoparticle mediated graphene plasmon for broadband enhanced infrared spectroscopy.

Graphene plasmonics, with dynamic tunable resonance wavelength, has been successfully used in broadband plasmon-enhanced infrared spectroscopy. However, the requirement for external voltage loading makes the practical application sophisticated. In this work, the hybrid structure of graphene nanodot array (GNA) and gold nanoparticles (AuNPs) has been proposed as a passive platform for broadband infrared absorption enhancement. Numerical simulations show that the plasmon resonance peak of GNA becomes stiffer and broader when introducing AuNPs, and this is also proved by experimental results that the vibrational modes of polyethylene oxide molecule in a broad spectral range can be simultaneously enhanced. The metal-graphene hybrid plasmonic system has been proved to be a promising candidate for infrared sensing, which is significant for safety and healthy applications.