Curculigoside Regulates Apoptosis and Oxidative Stress Against Spinal Cord Injury by Modulating the Nrf-2/NQO-1 Signaling Pathway In Vitro and In Vivo.

Spinal cord injury (SCI) is a severe neurological disorder that can lead to paralysis or death. Oxidative stress during SCI is a critical phase causing extensive nerve cell damage and apoptosis, thereby impairing spinal cord healing. Thus, a primary goal of SCI drug therapy is to mitigate oxidative stress. Curculigoside (CUR), a phenolic glucoside extracted from the dried root and rhizome of Curculigo orchioides Gaertn, possesses neuroprotective and antioxidant properties. This study aimed to investigate whether CUR effectively promotes the recovery of spinal cord tissue following SCI and elucidate its mechanism. We employed a hydrogen peroxide (H2O2)-induced PC12 cell model and an SCI rat model to observe the effects of CUR on oxidation and apoptosis. The results demonstrated that CUR significantly reduced the expression of apoptosis-related proteins (Bax and Caspase-3), Annexin V/propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while increasing the expression of the anti-apoptotic protein Bcl-2. Moreover, CUR effectively enhanced levels of antioxidants (glutathione [GSH)] and decreased reactive oxygen species (ROS) in vitro. Furthermore, CUR facilitated functional recovery through its anti-apoptotic and anti-oxidative stress effects on spinal cord tissues in SCI rats. These effects were mediated via the Nrf2/NQO1 signaling pathway. Therefore, our study showed that CUR acted as an anti-apoptotic and anti-oxidative stress agent, inhibiting astrocyte activation and promoting neuronal reconstruction and functional recovery. These findings may contribute significantly to the development of SCI treatments and advance the field of SCI drug therapy.

Transplantation of MiR-28-5p-Modified BMSCs Promotes Functional Recovery After Spinal Cord Injury.

Traumatic spinal cord injury (TSCI) is a prevalent central nervous system condition that imposes a significant burden on both families and society, affecting more than 2 million people worldwide. Recently, there has been increasing interest in bone marrow mesenchymal stem cell (BMSC) transplantation as a promising treatment for spinal cord injury (SCI) due to their accessibility and low immunogenicity. However, the mere transplantation of BMSCs has limited capacity to directly participate in the repair of host spinal cord nerve function. MiR-28-5p, identified as a key differentially expressed miRNA in spinal cord ischemia-reperfusion injury, exhibits differential expression and regulation in various neurological diseases. Nevertheless, its involvement in this process and its specific regulatory mechanisms in SCI remain unclear. Therefore, this study aimed to investigate the potential mechanisms through which miR-28-5p promotes the neuronal differentiation of BMSCs both in vivo and in vitro. Our results indicate that miR-28-5p may directly target Notch1, thereby facilitating the neuronal differentiation of BMSCs in vitro. Furthermore, the transplantation of lentivirus-mediated miR-28-5p-overexpressed BMSCs into SCI rats effectively improved footprint tests and Basso, Beattie, and Bresnahan (BBB) scores, ameliorated histological morphology (hematoxylin-eosin [HE] and Nissl staining), promoted axonal regeneration (MAP2 and growth-associated protein 43 [GAP43]), and facilitated axonal remyelination (myelin basic protein [MBP]). These findings may suggest that miR-28-5p-modified BMSCs could serve as a therapeutic target to enhance the behavioral and neurological recovery of SCI rats.

Protective Effect of Illicium Verum Extract On Vascularization In Rats With Osteoporotic Fracture.

Objective: To investigate the protective effect of Illicium verum extract on the vascularization of osteoporotic fracture in rats, and to elucidate its potential mechanism. Methods: The osteoporotic fracture model was established in ovariectomized rats. Rats were infused with 0.05 ml/kg extract in the stomach every morning. Eighteen rats are then divided into control group, model group, and Illicium verum extract group with 6 rats in each group. To observe the therapeutic effect of Illicium verum extract on osteoporotic rats. Femoral bone mineral density and elastic segment end-point load were evaluated by dual-energy x-ray absorptiometry and three-point bending test. Hematoxylin-eosin staining was used to measure the number and area of callus blood vessels. The serum levels of VEGF and NO were detected by ELISA. Moreover, the expressions of NOX2, NOX4, NRF2, p-PI3K, CyclinD1, VEGF, HIF1α, and eNOS in HUVEC were detected by Western blot. CCK8 and wound healing assay were used to detect the proliferation and migration of HUVEC. Then, the ability of HUVEC to form blood vessels was detected by tube formation assay. Results: Firstly, control group showed the normal pathomorphology and density of femoral bone, and model group showed significantly decreased bone density and consistent with bone microstructure degeneration, destruction, thinning, and fracture of bone trabecular structure vs control group, and illicium verum extract significantly increased femoral density and maximum load, increased the number and area of callus blood vessels and increased VEGF and NO levels in serum vs model group. Then, Illicium verum extract promoted the expression of NRF2, p-PI3K, CyclinD1, VEGF, HIF1α, and eNOS protein in HUVEC, inhibited the expression of NOX2 and NOX4, and enhanced the cell proliferation, migration, and angiogenesis. However, the effect was reversed by the overexpression of NRF2 and the treatment with LY294002. Conclusion: Illicium verum extract protects the vascularization of the osteoporotic fracture model in rats.

Tauroursodeoxycholic Acid Inhibited Apoptosis and Oxidative Stress in H2O2-Induced BMSC Death via Modulating the Nrf-2 Signaling Pathway: the Therapeutic Implications in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a prevalent and significant injury to the central nervous system, resulting in severe consequences. This injury is characterized by motor, sensory, and excretory dysfunctions below the affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a potential treatment for SCI. However, the low survival as well as the differentiation rates of BMSCs within the spinal cord microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (TUDCA), an active ingredient found in bear bile, has demonstrated its neuroprotective, antioxidant, and antiapoptotic effects on SCI. Thus, the present study was aimed to study the possible benefits of combining TUDCA with BMSC transplantation using an animal model of SCI. The results showed that TUDCA significantly enhanced BMSC viability and reduced apoptosis (assessed by Annexin V-FITC, TUNEL, Bax, Bcl-2, and Caspase-3) as well as oxidative stress (assessed by ROS, GSH, SOD, and MDA) both in vitro and in vivo. Additionally, TUDCA accelerated tissue regeneration (assessed by HE, Nissl, MAP2, MBP, TUJ1, and GFAP) and improved functional recovery (assessed by BBB score) following BMSC transplantation in SCI. These effects were mediated via the Nrf-2 signaling pathway, as evidenced by the upregulation of Nrf-2, NQO-1, and HO-1 expression levels. Overall, these results indicate that TUDCA could serve as a valuable adjunct to BMSC transplantation therapy for SCI, potentially enhancing its therapeutic efficacy.

Regression of a large prolapsed lumbar disc herniation achieved by conservative treatment: A case report and literature review.

A common spinal condition known as lumbar disc herniation (LDH) can result in radicular and low back discomfort. A 27-year-old man was admitted to our hospital with a 6-year history of persistent low back pain, and his low back pain had recurred with radiation to his lower extremities over the last two months. An extensive right-sided paracentral disc herniation in the L5/S1 intervertebral region, which compressed the nerve root, was discovered by magnetic resonance imaging (MRI) of his lumbar spine. After receiving conservative treatment, the patient reported that his lower back discomfort and neurogenic claudication had gradually subsided after 4 months. After one year, a follow-up MRI showed that the massive, prolapsed disc herniation at the L5/S1 level had totally disappeared. The sagittal protrusion length of the L5/S1 intervertebral disc shrank from 12.35 mm to 3.49 mm. However, there remained a chance of vertebral height loss. During the course of treatment, the height of the L5/S1 intervertebral space was still slightly reduced. The intervertebral space height declined from 7.705 mm to 7.201 mm after one year of treatment. The current case and a review of the literature demonstrate that LDH can decrease with conservative therapy over a short period of time. We stress the effectiveness of conservative treatment in very select LDH cases that lack a clear surgical justification.

Biomechanical study of femoral neck system for young patients with nonanatomically reduced femoral neck fractures: a finite element.

BACKGROUND: A consensus regarding the optimal approach for treating femoral neck fractures is lacking. We aimed to investigate the biomechanical outcomes of Femoral Neck System (FNS) internal fixation components in the treatment of nonanatomically reduced femoral neck fractures. METHOD: We constructed two types of femoral neck fractures of the Pauwels classification with angles of 30° and 50°, and three models of anatomic reduction, positive buttress reduction and negative buttress reduction were constructed. Subgroups of 1 to 4 mm were divided according to the distance of displacement in the positive buttress reduction and negative buttress reduction models. The von Mises stress and displacements of the femur and FNS internal fixation components were measured for each fracture group under 2100-N axial loads. RESULTS: When the Pauwels angle was 30°, the positive 1-mm and 2-mm models had lower FNS stress than the negative buttress model. The positive 3- and 4-mm models showed FNS stress similar to that of the negative buttress model. But the four positive buttress models had similar stresses on the femur as the negative buttress model. When the Pauwels angle was 50°, the four positive buttress models had higher FNS stress than the negative buttress model. Three positive buttress models (2 mm, 3 and 4 mm) resulted in lower stress of the femur than the negative buttress model, though the 1-mm model did not. When the Pauwels angle was 30°, the positive buttress model had a lower displacement of the FNS than the negative buttress model and a similar displacement of the femur with the negative buttress model. When the Pauwels angle was 50°, the positive buttress model had a higher displacement of the FNS and femur than the negative buttress model. Our study also showed that the von Mises stress and displacement of the internal fixation and the femur increased as the fracture angle increased. CONCLUSION: From the perspective of biomechanics, when the Pauwels angle was 30°, positive buttress was more stable to negative buttress. However, when the Pauwels angle was 50°, this advantage weakens. In our opinion, the clinical efficacy of FNS internal fixation with positive buttress may be related to the fracture angle, neck-shaft angle and alignment in the lateral view. This result needs verification in further clinical studies.

Effects of natural nanoparticles on the acute toxicity, chronic effect, and oxidative stress response of phenicol antibiotics in Daphnia magna.

Natural nanoparticles (NNP) are ubiquitous in natural water and can interact with other contaminants, causing ecotoxic effects on aquatic nontarget organisms. However, the impact of NNPs on the ecotoxicity of antibiotics remains largely unknown. This work investigated the acute toxicity, chronic effect, and oxidative response and damage in Daphnia magna co-exposed to phenicol antibiotics (chloramphenicol, thiamphenicol) and different concentrations of NNPs (10 mg/L: environmentally relevant concentration; 100 mg/L: a high concentration that caused no apparent immobilization in D. magna). The results showed that the acute toxicity of chloramphenicol was increased by 10 mg/L NNPs but decreased by 100 mg/L NNPs; both concentrations of NNPs increased and decreased acute toxicities of thiamphenicol and chloramphenicol + thiamphenicol treatments, respectively. After long-term exposure, phenicol antibiotics (1 µg/L) and NNP (10 mg/L) mixtures in environmentally relevant concentrations significantly affected the reproduction of D. magna but did not influence their growth. The catalase activity, reduced glutathione level, and malonaldehyde content in D. magna also varied with the NNPs concentrations. Notably, the lowest concentration of thiamphenicol and chloramphenicol + thiamphenicol combined with NNPs significantly increased the malondialdehyde content in D. magna compared with the control, indicating membrane lipid peroxidation occurred in daphnids. This study suggests that the toxic effects of contaminants and NNPs on aquatic organisms should be considered thoroughly to avoid underestimating the hazard of these pollutants in the actual aquatic environment.

Crochet Hook Technique for Arthroscopic Anterior Talofibular Ligament Repair: Technique Note.

Ankle sprains can lead to chronic lateral ankle instability caused by an injured anterior talofibular ligament (ATFL), and surgery is often required when conservative treatments fail. BROSTROM surgery is considered the gold standard and has a definite curative effect. Advancements in arthroscopic surgery and improvements in implanted anchors have led to an increase in ATFL repairs using arthroscopic surgery. Arthroscopic AFTL repair is less invasive, and patients could experience faster recovery compared to open AFTL repair. To simplify the complicated suture-passing processes in arthroscopic AFTL repair, we developed a crochet hook and loop wire technique, which is described in this paper.