Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Two quinoline-based two-photon fluorescent probes for imaging of viscosity in subcellular organelles of living HeLa cells.

Two viscosity-sensitive two-photon fluorescent probes (QL and QLS) were designed and synthesized, which can be localized in lysosome and mitochondria in living HeLa cells, respectively. As the increases of viscosity from 2.55 to 1150 cP, the fluorescence quantum yield (Φ) of QL and QLS was increased by 28-fold and 37-fold, respectively. At the same time, its effective two-photon absorption cross section (ΦδTPA) was enhanced by 15-fold and 16-fold, respectively. Fluorescence lifetime imaging (FLIM) of living HeLa cells stained with QL and QLS, revealed that lysosomal viscosity ranged from 100.76 to 254.74 cP and mitochondrial viscosity ranged from 92.21 to 286.79 cP. This type of fluorescent probe is helpful in the design and application of materials for monitoring diseases associated with abnormal viscosity.

Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch.

Toll-like receptors (TLRs) have been implicated in pain and itch regulation. TLR2, a TLR family member that detects microbial membrane components, has been implicated in pathologic pain. However, the role of TLR2 in pruritic and nociceptive responses has not been thoroughly investigated. In this study, we found that TLR2 was expressed in mouse dorsal root ganglia (DRG) and trigeminal ganglia (TG) neurons. Itch and pain behaviors, including histamine-dependent and histamine-independent acute itching, acetone/diethyl ether/water and 2,4-dinitrofluorobenzene-induced chronic itching and inflammatory pain, were largely attenuated in TLR2 knockout (KO) mice. The TLR2 agonist Pam3CSK4, which targets TLR2/1 heterodimers, evoked pain and itch behavior, whereas lipoteichoic acid (LTA) and zymosan, which recognize TLR2/6 heterodimers, produced only pain response. The TLR2 agonist-induced nociceptive and pruritic behaviors were largely diminished in transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) KO mice. Finally, Pam3Csk4 and zymosan increased the [Ca2+]i in DRG neurons from wild-type mice. However, the enhancement of [Ca2+]i was largely inhibited in the DRG neurons from TRPV1 and TRPA1 KO mice. Our results demonstrate that TLR2 is involved in different itch and pain behaviors through activating TLR1/TLR2 or TLR6/TLR2 heterodimers via TRPV1 and TRPA1 channels.

Regulation of optical properties for fluorescent triphenylamine-silver hybrid based on SPR effect.

In this study, a two photon absorbing (TPA) material consisting silver nanoparticles and triphenylamine-thiol derivative (TBS) has been prepared through interfacial coordination effect according to soft-hard-acid-base principle. The interfacial structure and morphology of the hybrid are researched in detail. Linear and nonlinear optical properties of the hybrid are studied. Upon interfacial coordination, the hybrid shows red-shifted UV-Vis absorption, causing from enhanced electronic drawing strength due to existence of Ag atom. The results also indicate that the surface Plasmon resonance (SPR) effect of Ag nanoparticles (~6 nm) brings about enhancement in single photon fluorescence emission and two photon absorption. Compared with free TBS, Ag-TBS hybrids show higher TPA cross-section (δ), which is 8784 GM for TBS and up to 103876 GM for Ag-TBS hybrid, showing ~12 fold increase. Due to excellent TPA property, the hybrids have good application in the field of optical power limiting and its limiting threshold is 0.49 J/cm-2. This type of interfacial coordination induced hybrid provides a promising strategy to regulate linear optical properties and optimize nonlinear performance.