Insulin-like growth factor 1 (IGF-1) is implicated in the nociceptive (pain) sensitivity of primary afferent neurons. We found that the IGF-1 receptor (IGF-1R) functionally stimulated voltage-gated T-type Ca(2+) (CaV3) channels in mouse dorsal root ganglia (DRG) neurons through a mechanism dependent on heterotrimeric G protein (heterotrimeric guanine nucleotide-binding protein) signaling. IGF-1 increased T-type channel currents in small-diameter DRG neurons in a manner dependent on IGF-1 concentration and IGF-1R but independent of phosphatidylinositol 3-kinase (PI3K). The intracellular subunit of IGF-1R coimmunoprecipitated with Gαo. Blocking G protein signaling by the intracellular application of guanosine diphosphate (GDP)-β-S or with pertussis toxin abolished the stimulatory effects of IGF-1. Antagonists of protein kinase Cα (PKCα), but not of PKCβ, abolished the IGF-1-induced T-type channel current increase. Application of IGF-1 increased membrane abundance of PKCα, and PKCα inhibition (either pharmacologically or genetically) abolished the increase in T-type channel currents stimulated by IGF-1. IGF-1 increased action potential firing in DRG neurons and increased the sensitivity of mice to both thermal and mechanical stimuli applied to the hindpaw, both of which were attenuated by intraplantar injection of a T-type channel inhibitor. Furthermore, inhibiting IGF-1R signaling or knocking down CaV3.2 or PKCα in DRG neurons abolished the increased mechanical and thermal sensitivity that mice exhibited under conditions modeling chronic hindpaw inflammation. Together, our results showed that IGF-1 enhances T-type channel currents through the activation of IGF-1R that is coupled to a G protein-dependent PKCα pathway, thereby increasing the excitability of DRG neurons and the sensitivity to pain.

Pinguecula is a condition of abnormal epithelial differentiation. It is characterized by squamous proliferation and metaplasia, resulting in instability of tear film with normal basic tear secretion.

The development of simple but sensitive methods for hyaluronidase (HAase) detection has been paid a great deal of attention because HAase is a potential cancer marker. In this work, a novel system coupled with a controlled release system has been designed for HAase determination without complex analytical instruments and skilled technicians. Pt@SiO 2 nanoparticles (NPs), which can catalyze the breakdown of H 2 O 2 into O 2 and H 2 O, was embedded in the hydrogel constructed by polyethylenimine (PEI) and hyaluronic acid (HA). In the presence of HAase, the hydrogel was broken down as HAase can catalyze the degradation of HA and hence the Pt@SiO 2 NPs in the hydrogel was released. The released Pt@SiO 2 NPs mixed with H 2 O 2 solution in a drainage device, and then O 2 was generated due to the decomposition of H 2 O 2 , resulting in an enhancement of pressure in the drainage device because of the low solubility of O 2 . A certain amount of H 2 O overflowed from the drainage device because the difference of the pressure between the inner and outer of the drainage device. The overflowed H 2 O was collected by a tube, and its amount was easily measured by an electronic balance. The weight of the H 2 O has a linear relationship with the HAase concentration in the range of 1−60 U/mL (120 min enzymatic hydrolysis time) and 0.2−10 U/mL (240 min enzymatic hydrolysis time). The developed system has been applied to detect the activity of HAase in urine samples with satisfied results.

This study aimed to investigate the efficacy of polydopamine nanoparticles (Pdop-NPs) as a subcutaneous antigen delivery vehicle in antitumor therapy. The nanoparticles were prepared by self-polymerization of dopamine in an aerobic and weak alkaline solution, and the tumor model antigen-ovalbumin (OVA) was grafted onto the nanoparticles to form OVA@Pdop nanoparticles (OVA@Pdop-NPs). The particle size of OVA@Pdop-NPs was 232.8 nm with a zeta potential of −23.4 mV, and the loading capacity of OVA protein was 754 μg mg–1. OVA@Pdop-NPs were essentially noncytotoxic and even demonstrated a slightly viability effect on bone-marrow-derived dendritic cells (BMDCs). As compared to free OVA, OVA@Pdop-NPs exhibited higher cellular uptake and were easier to migrate to lymph nodes in vivo. Both in vitro and in vivo experiments showed that OVA@Pdop-NPs promoted the maturation of DCs with up-regulated expression of major histocompatibility complex (MHC), costimulatory molecules, and cytokines. When used to treat the mice bearing OVA-MC38 colon tumor, OVA@Pdop-NPs could effectively activate OVA-specific cytotoxic CD8+ T cells and induce the production of memory CD4+ and CD8+ T cells and thus led to significantly suppressed tumor growth. All the preliminary data demonstrated the application potential of OVA@Pdop-NPs as a vaccine vector in cancer immunotherapy.

Systemic L-DOPA was partly effective in this guinea pig model and, therefore, is worth testing for effectiveness in progressing human myopes.