CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia.

Neuroinflammation is a crucial mechanism in many neurological disorders. Injury to the peripheral sensory nerves leads to a neuroinflammatory response in the somatosensory pathway, from dorsal root ganglia (DRG) to the spinal cord, contributing to neuropathic pain. How the immune reaction is initiated peripherally and propagated to the spinal cord remains less clear. Here, we find that ciliary neurotrophic factor (CNTF), highly expressed in Schwann cells, mediates neuroinflammatory response through the activating signal transducer and activator of transcription 3 (STAT3) and inducing interleukin 6 (IL-6) in sensory neurons. Cntf deficiency attenuates neuroinflammation in DRG and the spinal cord with alleviated pain post-injury. Recombinant CNTF applied to the sensory nerves recapitulates neuroinflammation in the DRG and spinal cord, with consequent pain development. We delineate the CNTF-STAT3-IL-6 axis in mediating the onset and progression of the inflammatory cascade from the periphery to the spinal cord with therapeutic implications for neuropathic pain.

DLK mediates the neuronal intrinsic immune response and regulates glial reaction and neuropathic pain.

Inflammatory response triggered by nerve injury plays important roles in the development of neurological disorders, such as neuropathic pain. The signaling events leading to inflammation in the nervous system remain poorly understood. Here, by deleting Dlk in sensory neurons driven by Wnt1a-Cre, we show that dual leucine zipper kinase (DLK) is required for the neuronal intrinsic immune response to induce cytokines and chemokines such as Ccl2, Ccl7, and Ccl12 upon nerve injury. The DLK-controlled injury response in sensory neurons could regulate CD11b+ immune cell infiltration in the dorsal root ganglia, as well as microgliosis and astrogliosis in the spinal dorsal horn but not the ventral horn. Deficiency of Dlk drastically alleviates the neuropathic pain elicited by chronic constriction injury of the sciatic nerve. Thus, DLK is an essential component that mediates the neuronal intrinsic immune response to nerve injury in sensory neurons and regulates inflammation in the spinal cord.

Splenic Leukocytes Get the Nerves up for Myelopoiesis.

The intricate interplay between the immune and the nervous systems has been steadily unveiled at both cellular and molecular levels. In this issue of Immunity, Vasamsetti et al. (2018) show that sympathetic nerves drive catecholamine signaling from leukocytes, thereby promoting splenic granulocyte macrophage progenitor (GMP) proliferation and differentiation.

Sources of varieties and quality of circular Fructus Ligustri Lucidi.

This study aimed to trace sources and quantitatively analyze the specnuezhenide content of circular Fructus Ligustri Lucidi for clinical use. Different specifications of Fructus Ligustri Lucidi were identified using DNA barcoding technology and the specnuezhenide content was analyzed by High Performance Liquid Chromatography (HPLC). The ITS sequence of circular Fructus Ligustri Lucidi was identical to that of standard privet, which was determined through botanical identification. ITS sequence similarity between circular Fructus Ligustri Lucidi and Fructus Ligustri Lucidi which was registered in NCBI ranged from 99.5% to 100%. The sequences of circular and other Fructus Ligustri Lucidi were clustered in a Neighbor-Joining tree with bootstrap value of 95, and these sequences could be distinguished from adulterants. Conforming to pharmacopoeia standard, the average specnuezhenide content of circular Fructus Ligustri Lucidi was higher than that of chicken waist Fructus Ligustri Lucidi. Circular Fructus Ligustri Lucidi derived from Ligustrum lucidum Ait. and the specnuezhenide content was higher in circular Fructus Ligustri Lucidi than that in chicken waist Fructus Ligustri Lucidi.

Biological and genomic analysis of a PBSX-like defective phage induced from Bacillus pumilus AB94180.

Defective prophages, which are found in the genomes of many bacteria, are unable to complete a viral replication cycle and propagate in their hosts as healthy prophages. They package random DNA fragments derived from various sites of the host chromosome instead of their own genomes. In this study, we characterized a defective phage, PBP180, which was induced from Bacillus pumilus AB94180 by treatment with mitomycin C. Electron microscopy showed that the PBP180 particle has a head with a hexagonal outline of ~40 nm in diameter and a long tail. The DNA packaged in the PBP180 head consists of 8-kb DNA fragments from random portions of the host chromosome. The head and tail proteins of the PBP180 particle consist of four major proteins of approximately 49, 33, 16 and 14 kDa. The protein profile of PBP180 is different from that of PBSX, a well-known defective phage induced from Bacillus subtilis 168. A killing activity test against two susceptible strains each of B. subtilis and B. pumilus showed that the defective particles of PBP180 killed three strains other than its own host, B. pumilus AB94180, differing from the host-killing ranges of the defective phages PBSX, PBSZ (induced from B. subtilis W23), and PBSX4 (induced from B. pumilus AB94044). The genome of the PBP180 prophage, which is integrated in the B. pumilus AB94180 chromosome, is 28,205 bp in length, with 40 predicted open reading frames (ORFs). Further genomic comparison of prophages PBP180, PBSX, PBSZ and other PBSX-like prophage elements in B. pumilus strains revealed that their overall architectures are similar, but significant low homology exists in ORF29-ORF38, which presumably encode tail fiber proteins involved in recognition and killing of susceptible strains.

[The preparation and kinetic study on enzymatically-controlled drug release of isotretinoin/amylose inclusion complex].

The inclusion complex of isotretinoin was prepared by sealed-control temperature method and amylose was used as carrier. The formation of inclusion complex was confirmed by powder X-ray diffraction and DSC. The equation of enzymatically-controlled drug release was established by kinetic theory, and the release characteristic of drug was confirmed by using the kinetic equation. The results show that the drug release was attributed to first order reaction without alpha-amylase. However, with alpha-amylase, the drug release was an acceleration process by the effect of both dissociation and enzymatic hydrolysis simultaneously. The research indicates that drug release from the inclusion complex was modulated by the addition of alpha-amylase.