The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death. Cell free-double strand DNA (dsDNA) segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase (cGAS), which triggers robust activation of the innate immune stimulator of interferon genes (STING) pathway and initiate the chronic inflammatory cascade. The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation. To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination, we constructed a DNase-mimetic artificial enzyme loaded with C-176. Nanoparticles are self-assembled by amphiphilic copolymers (P[CL₃₅-b-(OEGMA_20.7-co-NTAMA_14.3)]), C-176, and Ce⁴⁺ which is coordinated with nitrilotriacetic acid (NTA) group to form corresponding catalytic structures. Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce⁴⁺ enzyme and STING inhibitor synergistically. In conclusion, it is a novel approach to modulating central nervus system (CNS) inflammatory signaling pathways and improving stroke prognosis.

Aims: The primary aim of this study was to assess if traumatic triangular fibrocartilage complex (TFCC) tears can be treated successfully with immobilization alone. Our secondary aims were to identify clinical factors that may predict a poor prognosis.Methods: This was a retrospective analysis of 89 wrists in 88 patients between January 2015 and January 2019. All patients were managed conservatively initially with either a short-arm or above-elbow custom-moulded thermoplastic splint for six weeks. Outcome measures recorded included a visual analogue scale for pain, Patient-Rated Wrist Evaluation, Disabilities of the Arm, Shoulder and Hand score, and the modified Mayo Wrist Score (MMWS). Patients were considered to have had a poor outcome if their final MMWS was less than 80 points, or if they required eventual surgical intervention. Univariate and logistic regression analyses were used to identify independent predictors for a poor outcome.Results: In total, 76% of wrists (42/55) treated with an above-elbow splint had a good outcome, compared to only 29% (10/34) with a short-arm splint (p < 0.001). The presence of a complete foveal TFCC tear (p = 0.009) and a dorsally subluxated distal radioulnar joint (DRUJ) (p = 0.032) were significantly associated with a poor outcome on univariate analysis. Sex, age, energy of injury, hand dominance, manual occupation, ulnar variance, and a delay in initial treatment demonstrated no significant association. Multiple logistic regression revealed that short-arm immobilization (p < 0.001) and DRUJ subluxation (p = 0.020) were significant independent predictive factors of an eventual poor outcome.Conclusion: Nonoperative management of traumatic TFCC injuries with above-elbow immobilization is a viable treatment method, particularly in patients without DRUJ subluxation. Early surgery should be considered for patients with dorsal ulnar subluxation treated with short-arm splints to prevent prolonged morbidity. Cite this article: Bone Joint J 2021;103-B(8):1386–1391.

Although bone marrow-derived mesenchymal stem cells (BMSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing and fibrosis alleviation, the underlying molecular mechanisms have been poorly understood. Moreover, transforming growth factor beta 1 (TGF-β1) is positively correlated with scar formation, whereas TGF-β3 inhibits the pathological scar formation process. However, the relation of TGF-β1, TGF-β3, and the TGF-β/Smad signaling pathway with BMSCs is unknown and requires further investigation. A cell co-culture platform was used to examine the relationship between BMSCs and dermal fibroblasts (DFs). EdU labelling and cell cycle detection were carried out to examine the viability of DF cells. Transwell and wound healing assays were used to test the cell migration of DFs. The expression of TGF-β pathway components and collagens were determined by RT-qPCR and western blotting. A damaged skin rat model was applied to test the effects of BMSC treatment on skin wound healing. The results showed that BMSC secretion could inhibit the viability and migration of DFs. Moreover, we observed that the TGF-β-induced expression of TGF-β1, Smad2, Smad3, COLI and COLIII was attenuated upon BMSC treatment in DFs, while the decrease in TGF-β3 expression was enhanced by BMSCs. Furthermore, BMSC treatment accelerated wound healing and attenuated skin collagen deposition in a damaged skin rat model, leading to the mitigation of cell proliferation and enhancement of cell apoptosis. In addition, the expression of alpha-smooth muscle actin (α-SMA), COLI, and COLII was alleviated by BMSC treatment. Our results indicate that BMSCs can promote wound healing and inhibit skin collagen deposition, which is associated with the TGF-β/Smad signaling pathway.

Low back pain is the leading cause of disability worldwide. Intervertebral disc degeneration (IDD) is the primary clinical risk factor for low back pain and the pathological cause of disc herniation, spinal stenosis, and spinal deformity. A possible approach to improve the clinical practice of IDD-related diseases is to incorporate biomarkers in diagnosis, therapeutic intervention, and prognosis prediction. IDD pathology is still unclear. Regarding molecular mechanisms, cellular signaling pathways constitute a complex network of signaling pathways that coordinate cell survival, proliferation, differentiation, and metabolism. Recently, stem cells have shown great potential in clinical applications for IDD. In this review, the roles of multiple signaling pathways and related stem cell treatment in IDD are summarized and described. This review seeks to investigate the mechanisms and potential therapeutic effects of stem cells in IDD and identify new therapeutic treatments for IDD-related disorders.

During interventional surgeries of implantable cardiovascular devices in addressing cardiovascular diseases (CVD), the inevitable tissue damage will trigger host inflammation and vascular lumen injury, leading to delayed re-endothelization and intimal hyperplasia. Endowing cardiovascular implants with anti-inflammatory and endothelialization functions is conducive to the target site, offering significant tissue repair and regeneration benefits. Herein, inspired by the snake's molting process, a ShedWise device was developed by using the poly(propylene fumarate) polyurethane (PPFU) as the foundational material, which was clicked with hyperbranched polylysine (HBPL) and followed by conjugation with pro-endothelial functional Arg-Glu-Asp-Val peptide (REDV), and finally coated with a “self-sacrificing” layer having reactive oxygen species (ROS)-scavenging ability and degradability. During the acute inflammation in the initial stage of implantation, the ROS-responsive hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol (HBPAK) coating effectively modulated the level of environmental inflammation and resisted initial protein adsorption, showcasing robust tissue protection. As the coating gradually “sacrificed”, the exposed hyperbranched HBPL-REDV layer recruited specifically endothelial cells and promoted surface endothelialization. In a rat vascular injury model, the ShedWise demonstrated remarkable efficiency in reducing vascular restenosis, protecting the injured tissue, and fostering re-endothelization of the target site. This innovative design will introduce a novel strategy for surface engineering of cardiovascular implants and other medical devices.

In recent decades, the limitations of therapeutic interventions have elevated neurological disorders and injuries to a prominent position in academic research. Existing neurotherapeutic methodologies have demonstrated insufficient efficacy in fostering neural regeneration. The current integration of precision medicine technologies and innovative tissue engineering methods holds significant promise for attaining neural regeneration. The cGAS–STING pathway, a pivotal component of the innate immune system, plays a crucial role in the pathological processes of various neurological diseases and injuries. In neuroinflammatory diseases and neural injuries, aberrant activation of the cGAS–STING pathway amplifies neuroinflammation, type I interferon responses, and cell death. Inhibition of cGAS–STING-related genes holds promise for promoting neural regeneration following disease recovery and defect regeneration. In this review, the foundational pathophysiological mechanisms underlying cGAS–STING-related gene regulation in neurological disorders and injuries are elucidated with a special emphasis on its implications in nerve-related cells. In this review, we highlight the advances in tissue engineering technologies that integrate cGAS–STING pathway modulators, highlighting their potential therapeutic efficacy in modulating neural regeneration. Nevertheless, the role of the cGAS–STING pathway in neural regeneration remains relatively limited. Bibliometric analysis demonstrates a significant correlation of cGAS–STING pathway activation with various neuropathological processes. Studies have progressively focused on the critical role of this pathway in neurological diseases and injuries. As it stands, the effectiveness of tissue engineering technologies involving cGAS–STING-related gene modulators in achieving neural regeneration remains unfulfilled in its potential. Future research must apply advanced omics technologies to further delineate the exact functions of the cGAS–STING pathway in neural regeneration. Integration of these results with precision medicine approaches will be necessary for creating tissue engineering biomaterials with capabilities for precise delivery and targeted controlled release of cGAS–STING-related genes in neural regeneration-related cells, towards functional recovery from neurological injury and diseases.