The challenge of healing diabetic skin wounds presents a significant hurdle in clinical practice and scientific research. In response to this pressing concern, we have developed a temperature-sensitive, in situ-forming hydrogel comprising poly(n-isopropylacrylamide₁₆₆-co-n-butyl acrylate₉) -poly(ethylene glycol) -poly(n-isopropylacrylamide₁₆₆-co-butyl acrylate₉) copolymer, denoted as PEP, in combination with zinc oxide nanoparticles, forming what we refer to as PEP-ZnO hydrogel. The antimicrobial properties of the PEP-ZnO hydrogel against methicillin-resistant Staphylococcus aureus were rigorously assessed by using the bacteriostatic banding method. In vitro evaluations encompassed examinations of hemocompatibility and biocompatibility. The study further employed a diabetic Sprague-Dawley (SD) rat whole-layer trauma model for comprehensive in vivo analyses. In vivo healing assessments revealed the potential of the PEP-ZnO hydrogel, characterized by increased collagen deposition and enhanced vascularization at the trauma site, thus significantly expediting the healing process. Collectively, these findings endorse the PEP-ZnO hydrogel as a safe and effective dressing for addressing chronic wounds in diabetic patients. This hydrogel not only holds promise for improving the quality of life for diabetic individuals grappling with chronic wounds but also represents a noteworthy advancement in wound care.

Diabetic foot is a major complication of diabetes. The bone transverse transport method could be applied in clinics for treatment, which could improve the metabolism of the tissues via lasting distraction forces. However, the process’ specific regulating mechanism is still unknown. Based on the notion that the healing of bones involves the recruitment of calcium ions, in this study, we established the model of tibial cortex transverse transport (TTT) on rats and then used tissue immunologic detection, such as the double fluorescent staining to explore the expression of the calcium channels’ calcium release-activated calcium modulator 1 (Orai1)/stromal interaction molecule 1 (STIM1), which belong to the store-operated calcium entry (SOCE) signaling pathways on the tissues around the bone transport area. By using the laser capture microdissection (LCM) tool, we acquired samples of tissues around the bone and endeavored to identify pivotal protein molecules. Subsequently, we validated the functions of key protein molecules through in vitro and in vivo experiments. After protein profile analysis, we found the differentially expressed key protein osteopontin (OPN). The in vitro experiments verified that, being stimulated by OPN, the migration, proliferation, and angiogenesis of human umbilical vein endothelial cells (HUVEC) were observed to be enhanced. The activation of Orai1/STIM1 might increase the activity of endothelial nitric oxide synthase (eNOS) and its effect on releasing nitric oxide (NO). Subsequently, the migration and proliferation of the HUVECs are improved, which ultimately accelerates wound healing. These signaling pathway was also observed in the OPN-stimulated healing process of the skin wound surface of diabetic mice. This study identifies the molecular biological mechanism of OPN-benefited the migration and proliferation of the HUVECs and provides ideas for searching for new therapeutic targets for drugs that repair diabetes-induced wounds to replace invasive treatment methods. The OPN is highly expressed in the tissues surrounding the TTT bone transfer area, which may possibly stimulate the activation of eNOS to increase NO release through the SOCE pathway mediated by Orai1/STIM1. This mechanism may play a significant role in the angiogenesis of diabetic foot's wounds promoted by TTT, providing new therapeutic strategies for the non-surgical treatment for this disease.

Background: Knee osteoarthritis (KOA) is a degenerative joint disease characterized by cartilage degradation, synovial inflammation, and joint pain. The infrapatellar fat pad (IFP) has been suggested to play a role in modulating the inflammatory processes in KOA. Excision of the IFP is considered a potential therapeutic approach to reduce inflammation and slow disease progression. Methods: A mouse model of KOA was used to evaluate the impact of IFP excision on inflammation. Mice were divided into five groups: sham (control), unexcised IFP, quarter excision, partial excision, and complete excision of the IFP. Knee joints were collected at early, middle, and late stages of KOA. Gait analysis, micro-computed tomography (micro-CT), HE staining, Safranin O-Fast Green staining, and immunohistochemistry (IHC) were performed to assess joint stability, bone changes, and inflammatory markers (MMP-3, IL-6, TNF-α, COL-2). qRT-PCR was conducted for cartilage tissue analysis. Results: Partial IFP excision significantly improved joint stability, particularly in the middle and late stages of KOA. Micro-CT analysis showed increased bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) in excised groups, with the most significant effects in the partial and complete excision groups. IHC and qRT-PCR indicated reduced MMP-3, IL-6, and TNF-α levels in excised groups, particularly in the partial and complete excision groups, suggesting reduced inflammation. COL-2 expression was higher in excised groups, particularly in late-stage KOA, indicating cartilage protection. The partial excision group exhibited the most balanced reduction in inflammation and improved cartilage integrity across all disease stages. Conclusion: IFP excision, especially partial excision, significantly modulates the inflammatory response in KOA. Partial excision showed the most effective and balanced impact on joint stability, bone integrity, and cartilage protection, offering potential as a therapeutic approach for KOA.

Stroke is one of the leading causes of death. (D-ala2, D-leu5) enkephalin (DADLE) is a synthetic peptide and highly selective delta opioid receptor (δOR) agonist that has exhibited protective properties in ischemia. However, the specific target and mechanism are still unclear. The present study explores the expression of δOR on brain microvascular endothelial cells (BMECs) and whether DADLE could relieve I/R-induced injury by reducing apoptosis. A lateral ventricular injection of DADLE for pretreatment, the neurofunctional behavior score, and TTC staining, were used to evaluate the protective effect of DADLE. Immunofluorescence technology was used to label different types of cells with apoptosis-positive signals to test co-localization status. Primary cultured BMECs were separated and treated with DADLE, accompanied by OGD/R. The CCK-8 test was conducted to evaluate cell viability and TdT-mediated dUTP Nick-end Labelling (TUNEL) staining to test apoptosis levels. The levels of apoptosis-related proteins were analyzed by Western blotting. The co-localization results showed that BMECs, but not astrocytes, microglia, or neurons, presented mostly TUNEL-positive signals, especially in the Dentate gyrus (DG) area of the hippocampus. Either activation of δORs on rats’ brains or primary BMECs mainly reduce cellular apoptosis and relieve the injury. Interference with the expression δOR could block this effect. DADLE also significantly increased levels of Bcl-2 and reduced levels of Bax. δOR’s expressions can be detected on the BMECs, but not on the HEK293 cells, by Western blotting and IFC. Therefore, DADLE exerts a cytoprotective effect, primarily under hypoxia-ischemic injury/reperfusion conditions, by targeting BMECs to inhibit apoptosis.

The ongoing debate regarding the excision of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains a contentious issue, with established parameters for IPFP management still lacking. Excessive resection of IPFP tissue may lead to patellar tendon (PT) shortening and reduced mobility of the knee joint. This study aims to evaluate whether the resection of pathologically altered IPFP tissue during TKA affects knee joint function and PT dimensions. A total of 100 patients with end-stage knee osteoarthritis (KOA) who successfully underwent their first TKA were randomly assigned to two groups: one group received resection of the pathologically altered IPFP tissue, while the other group underwent complete resection of all IPFP tissue. The excised IPFP specimens were subjected to pathological and immunohistochemical analysis. Patients underwent X-ray and MRI assessments prior to surgery, as well as at 6 weeks and 6 months postoperatively; additionally, the Numeric Rating Scale (NRS), Knee Injury and Osteoarthritis Outcome Scale (KOOS), and Oxford Knee Score (OKS) were utilized for evaluation. Furthermore, patellar tendon length and thickness were assessed. Histological examination of the IPFP tissue from patients with KOA revealed that not all IPFP specimens exhibited lesions under hematoxylin and eosin (HE) staining and immunohistochemical analysis, with lesion areas predominantly localized near the synovium. There was no significant difference in the NRS scores between the two patient groups at 6 weeks or 6 months postoperatively (Mann-Whitney test, P = 0.391; P = 0.055). However, a significant difference was observed in both KOOS and OKS between the two groups at 6 months after surgery (Mann-Whitney test, P < 0.05). Sonographic evaluation of patellar tendon parameters indicated a significant difference in PT thickness between the two groups only at 6 weeks postoperatively (Mann-Whitney test, P < 0.05). This study demonstrated that the resection of pathologically altered IPFP tissue during TKA in patients with end-stage KOA can significantly enhance early postoperative knee joint mobility, improve life satisfaction, and mitigate the impact on PT structure.

Spinal Cord Injury (SCI) is a severe disorder of the central nervous system, typically caused by trauma or disease, which significantly impacts the quality of life of affected individuals. Secondary inflammation following spinal cord injury is a critical factor influencing prognosis, making the exploration of the inflammatory microenvironment crucial for the treatment of SCI. Xanthoxylin, a small organic molecule extracted from plants, has demonstrated notable anti-inflammatory effects. To investigate the role of Xanthoxylin in spinal cord injury, we initially employed Hoechst staining and flow cytometry, revealing that Xanthoxylin reduces neuronal apoptosis. Subsequently, through Western blot, immunofluorescence, and qPCR, we discovered that Xanthoxylin promotes the polarization of microglia from the M1 inflammatory phenotype to the M2 anti-inflammatory phenotype. Furthermore, transcriptome sequencing identified differential expression in the NF-κB pathway, which was corroborated by Western blot analysis. Finally, animal experiments were conducted to further validate the therapeutic effects of Xanthoxylin on spinal cord injury in mice. These results suggest that Xanthoxylin has a significant therapeutic effect on SCI in mice. Overall, our study is the first to demonstrate the therapeutic effect of Xanthoxylin on SCI and provides a scientific exploration of its underlying mechanisms, offering new directions for pharmacological treatment of spinal cord injury.