Reduction of the trans-cortical vessel was associated with bone loss, another underlying mechanism of osteoporosis.

RATIONALE: Numerous studies have established a robust association between bone morrow microvascular diseases and osteoporosis. This study sought to investigate the relationship between alterations in trans-cortical vessel (TCVs) and the onset of osteoporosis in various mouse models. METHODS: Aged mice, ovariectomized mice, and db/db mice, were utilized as osteoporosis models. TCVs in the tibia were detected using tissue clearing and light sheet fluorescence microscopy imaging. Femurs bone mass were analyzed using micro-CT scanning. Correlations between the number of TCVs and bone mass were analyzed using Pearson correlation analysis. RESULTS: All osteoporosis mouse models showed a significant reduction in the number of TCVs compared to the control group. Correlation analysis revealed a positive association between the number of TCVs and bone mass. TCVs were also expressed high levels of CD31 and EMCN proteins as type H vessels. CONCLUSIONS: This study underscores a consistent correlation between the number of TCVs and bone mass. Moreover, TCVs may serve as a potential biomarker for bone mass evaluation.

Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

Efficient Synthesis of Cyclic Poly(ethylene glycol)s under High Concentration Conditions by the Assistance of Pseudopolyrotaxane with Cyclodextrin Derivatives.

An efficient synthesis of cyclic polymers (CPs) is in high demand due to their unique properties. However, polymer cyclization generally occurs at low concentrations (0.1 g/L), and the synthesis of CPs at high concentrations remains a challenge. Herein an efficient cyclization of poly(ethylene glycol) (Mn = 2000 g/mol, 4000 g/mol) (PEG-2k, PEG-4k) in high concentration (80 g/L) is realized by the assistance of pseudopolyrotaxane (pPRx). Water-soluble pPRx with a U-like-shape inclusion motif is prepared by mixing the 2-hydroxypropyl-γ-cyclodextrin (HPγCD) and PEG with (E)-3,4,5-trimethoxycinnamate (TCA-PEG-2k, TCA-PEG-4k). Subsequent irradiation of the pPRx solution (10-80 g/L) by UV light gives cyclic polymers through the intramolecular [2 + 2] photocycloaddition of the cinnamoyl moieties. The photoreaction of TCA-PEG-2k in the pPRx system gives cyclic monomers (C-1mer) as major products with a yield of 66% at 80 g/L. Additionally, the cyclization of TCA-PEG-4k also gives C-1mer as major products with a yield of 45% at a concentration of 80 g/L.

The role of PI3K/Akt signalling pathway in spinal cord injury.

Spinal cord injury (SCI) is a severely disabling central nervous system injury with complex pathological mechanisms that leads to sensory and motor dysfunction. The current treatment for SCI is aimed at symptomatic symptom relief rather than the pathological causes. Several studies have reported that signaling pathways play a key role in SCI pathological processes and neuronal recovery mechanisms. The PI3K/Akt signaling pathway is an important pathway closely related to the pathological process of SCI, and activation of this pathway can delay the inflammatory response, prevent glial scar formation, and promote neurological function recovery. Activation of this pathway can promote the recovery of neurological function after SCI by reducing cell apoptosis. Based on the role of the PI3K/Akt pathway in SCI, it may be a potential therapeutic target. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in SCI-induced inflammatory response, apoptosis, autophagy, and glial scar formation. We also summarize the latest evidence on treating SCI by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of SCI, and identify potential challenges in developing these clinical therapeutic SCI strategies, and provide appropriate solutions.