[Advances in genetic studies of Charcot-Marie-Tooth disease type 4 (CMT4)].

The Charcot-Marie-Tooth disease (CMT) is one of the most common human inherited peripheral neuropathies. The most common pattern of inheritance is autosomal dominant, with less often occurrence autosomal recessive and X-linked dominant/recessive inheritance. CMT is generally divided into three forms: demyelinating forms (CMT1), axonal forms (CMT2) and intermediate forms (DI-CMT). The autosomal recessive form (AR-CMT1 or CMT4) is accompanied by progressive distal muscle weakness and atrophy of the limbs, pes cavus and claw-like hands. In addition, CMT4 is also characterized by early onset, rapid progression, and varying degrees of sensory loss and spinal deformities (e.g. scoliosis). Recently, 11 subtypes of CMT4 have been identified. Some of these subtypes were clear in pathogenic mechanisms, some had founder mutation, but some still had limited clinical description and mutation analysis. In this review, we summarize the latest research progresses of CMT4, including genotypes and phenotypes, pathogenic mechanisms and mouse models.

Porous Se@SiO2 nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.