Capsaicin Enhanced the Efficacy of Photodynamic Therapy Against Osteosarcoma via a Pro-Death Strategy by Inducing Ferroptosis and Alleviating Hypoxia.

Ferroptosis, a novel form of nonapoptotic cell death, can effectively enhance photodynamic therapy (PDT) performance by disrupting intracellular redox homeostasis and promoting apoptosis. However, the extremely hypoxic tumor microenvironment (TME) together with highly expressed hypoxia-inducible factor-1α (HIF-1α) presents a considerable challenge for clinical PDT against osteosarcoma (OS). Hence, an innovative nanoplatform that enhances antitumor PDT by inducing ferroptosis and alleviating hypoxia is fabricated. Capsaicin (CAP) is widely reported to specifically activate transient receptor potential vanilloid 1 (TRPV1) channel, trigger an increase in intracellular Ca2+ concentration, which is closely linked with ferroptosis, and participate in decreased oxygen consumption by inhibiting HIF-1α in tumor cells, potentiating PDT antitumor efficiency. Thus, CAP and the photosensitizer IR780 are coencapsulated into highly biocompatible human serum albumin (HSA) to construct a nanoplatform (CI@HSA NPs) for synergistic tumor treatment under near-infrared (NIR) irradiation. Furthermore, the potential underlying signaling pathways of the combination therapy are investigated. CI@HSA NPs achieve real-time dynamic distribution monitoring and exhibit excellent antitumor efficacy with superior biosafety in vivo. Overall, this work highlights a promising NIR imaging-guided "pro-death" strategy to overcome the limitations of PDT for OS by promoting ferroptosis and alleviating hypoxia, providing inspiration and support for future innovative tumor therapy approaches.

M2 macrophage exosome-derived Apoc1 promotes ferroptosis resistance in osteosarcoma by inhibiting ACSF2 deubiquitination.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. The aim of this study was to investigate the regulatory mechanisms of M2 macrophage exosomes (M2-Exos) in ferroptosis in OS. A mouse model was established to investigate the in vivo role of M2-Exos. We investigated their effects on ferroptosis in OS using erastin, a ferroptosis activator, and deferoxamine mesylate, an iron chelator. In vitro, we investigated whether the Apoc1/Acyl-CoA Synthetase Family Member 2 (ACSF2) axis mediates these effects, using shApoc1 and shACSF2. The mechanisms whereby Apoc1 regulates ACSF2 were examined using cyclohexanone, a protein synthesis inhibitor, and MG132, a proteasomal inhibitor. M2-Exos reversed the inhibitory effects of erastin on OS cells, thus enhancing their viability, migration, invasion, proliferation, and reducing ferroptosis. Apoc1 was highly expressed in M2-Exos, and interfering with this expression reversed the effects of M2-Exos on OS cells. ACSF2 mediated the effects of M2-Exos-derived Apoc1. Apoc1 interacted with ACSF2, which, in turn, interacted with USP40. Apoc1 overexpression increased ACSF2 ubiquitination, promoting its degradation, whereas USP40 overexpression inhibited ACSF2 ubiquitination and promoted its expression. Apoc1 overexpression inhibited ACSF2 binding to USP40. M2-Exos-derived Apoc1 promoted ferroptosis resistance by inhibiting USP40 binding to ACSF2 and promoting ACSF2 ubiquitination and degradation, thus enhancing OS development.

The Impact of Sarcopenia on the Clinical Outcomes of Percutaneous Kyphoplasty in Patients With Osteoporotic Vertebral Compression Fracture: A Retrospective Cohort Study.

Objective: This study aimed to explore the impact of sarcopenia on clinical outcomes after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF). Methods: We retrospectively analyzed the medical records of patients with single-segment OVCF who underwent percutaneous kyphoplasty (PKP) between September 2021 and August 2022. Patients were categorized into a sarcopenia group (43 patients) and a non-sarcopenia group (125 patients) based on their Advanced Skeletal Muscle Index (ASMI). Clinical and radiological data were collected and analyzed. Results: There were no significant differences between the sarcopenia and non-sarcopenia groups in age, sex, bone mineral density (BMD), body mass index (BMI), fractured segment, fracture type, surgical approach, bone cement volume, bone cement distribution, comorbidities, preoperative and immediate postoperative VAS and ODI scores (P > .05). However, the time to ambulation, hospital stays, VAS and ODI scores at follow-up, excellent/good rate, and the incidence of residual pain and re-fractures in the non-sarcopenia group were significantly better than those in the sarcopenia group (P < .05). Meanwhile, radiological outcomes, including regional kyphosis and vertebral height loss rate, were significantly better in the non-sarcopenia group than in the sarcopenia group at 6 and 12 month follow-ups (P < .05). Conclusion: Clinical outcomes after PKP in patients with OVCF could be negatively affected by sarcopenia. Therefore, prevention and treatment of sarcopenia should be actively considered in the management of patients with OVCF.

Comparison of clinical outcomes between unilateral biportal endoscopic discectomy and percutaneous endoscopic interlaminar discectomy for migrated lumbar disc herniation at lower lumbar spine: a retrospective controlled study.

BACKGROUND: Both Unilateral Biportal Endoscopic Discectomy (UBED) and Percutaneous Endoscopic Interlaminar Discectomy (PEID) have resulted in favorable clinical outcomes in the management of LDH. The aim of this study is to comprehensively compare the efficacy of UBED and PEID in treating migrated LDH in the lower lumbar spine, with a specific focus on high-grade migrated LDH. METHODS: 96 patients who underwent UBED (31 cases) and PEID (65 cases) procedures were enrolled in the study. All patients received a minimum follow-up period of 6 months. Clinical outcomes of the patients were assessed with incision length, operation time, total hemoglobin loss, hospital stay, intraoperative fluoroscopy times, visual analogue scale (VAS) for lower back and leg pain, Oswestry disability index (ODI), modified MacNab criteria, complications, area of lamina loss and increased intervertebral height. RESULTS: The VAS scores for lower back and leg pain and ODI significantly decreased in both groups after the operation. Preoperatively, at 1 day, 1 month, and 6 months after the procedure, the VAS and ODI scores exhibited no significant differences between the two groups. There was no significant difference in terms of modified MacNab criteria, area of lamina loss, and increased intervertebral height. The UBED group had a longer incision length, operation time and postoperative hospital stay, and fewer intraoperative fluoroscopy times than to the PEID group. Complications were noted in both groups throughout the follow-up period, but there was no significant difference in the rate of complications. Moreover, there were no notable differences in clinical outcomes between the two groups in the high-grade migrated LDH. CONCLUSIONS: Both UBED and PEID could achieve favorable clinical outcomes for treating migrated LDH at the lower lumbar spine. Despite the longer operative time and postoperative hospital stay associated with the UBED group, UBED remains safe and innovative for treating migrated LDH at the lower lumbar spine.

Percutaneous Vertebroplasty for Cervical Symptomatic Hemangiomas and Spinal Metastases: A Case Series and Literature Review.

OBJECTIVE: Percutaneous vertebroplasty (PVP) is a commonly used technique for the treatment of spinal diseases, but it is rarely employed for cervical lesions. This study presents a case series and a literature review to evaluate the efficacy of cervical PVP. METHODS: From August 2013 to January 2023, 14 patients underwent cervical PVP in the author's institution. The mean postoperative follow-up time was 20.3 ± 12.1 months (ranging from 5 to 41 months). The pain status and quality of life were assessed preoperatively, postoperatively, and during follow-up using the Visual Analog Scale and Neck Disability Index. Additionally, complications that occurred during the study period were documented. RESULTS: The series of cases included 9 cases of hemangiomas and 5 cases of spinal metastases. The common symptom was axial pain in the neck. All patients were successfully treated with PVP. Visual analog scale scores decreased from 6.6 ± 0.8 preoperatively to 1.9 ± 0.8 at 24 hours postoperatively and to 2.4 ± 1.2 at the last follow-up (P < 0.01). Neck Disability Index decreased from 22.3% ± 8.9% preoperatively to 7.6% ± 8.1% at 24 hours postoperatively and to 6.0% ± 7.2% at 12-month follow-up (P < 0.01). After the operation, a case of dysphagia occurred, but no major complications were observed during the follow-up period. CONCLUSIONS: Cervical PVP via the anterolateral approach is a safe option for the treatment of cervical symptomatic hemangiomas and spinal metastases with limited invasiveness. It is effective in relieving pain and improving quality of life.

Exosomal LncRNA TM7SF3-AU1 Aggravates White Matter Injury via MiR-702-3p/SARM1 Signaling After Subarachnoid Hemorrhage in Rats.

Subarachnoid hemorrhage (SAH) is a devastating disease associated with a high mortality and morbidity. Exosomes have been considered as a potential therapeutic target for SAH. However, the effect of exosomes in SAH remains to be elucidated. In this study, we focused on investigating the effect of plasma exosomal lncRNA TM7SF3-AU1 in white matter injury after SAH. The SAH model was established by means of endovascular perforation. Exosomes were extracted from rat plasma samples. The expression of RNAs in the exosomes was detected by the transcriptomic microarray. Differentially expressed circRNA, lncRNA, and mRNA were obtained. The ceRNA network showed that the lncRNA TM7SF3-AU1 and miR-702-3p were closely associated with SARM1. Knocking down TM7SF3-AU1 promoted the expression of miR-702-3p and suppressed the expression of SARM1, and knocking down TM7SF3-AU1 also attenuated white matter injury after SAH. In addition, knocking down TM7SF3-AU1 improved the neurological deficits in locomotion, anxiety, learning, memory, and electrophysiological activity after SAH. Mechanistically, TM7SF3-AU1 was able to absorb miR-702-3p, which directly bind the SARM1 mRNA. Furthermore, the white matter injury attenuated by knockdown of TM7SF3-AU1 was partially reversed by the miR-702-3p antagomir in SAH rats. Taken together, this study showed that TM7SF3-AU1 acts as a sponge for miR-702-3p, reducing the inhibitory effect of miR-702-3p on SARM1, resulting in increased SARM1 expression and thus leading to white matter injury after SAH. Our study provides new insights into exosome-associated white matter injury. It also highlights TM7SF3-AU1 as a potential therapeutic target for white matter injury after SAH.

The therapeutic effect of sufficient oxygen-rich PRP injection in facial rejuvenation by multiple objective evaluations in 26 cases.

Background: Ozone can enhance the expression of some growth factors (GFs) in platelet rich plasma (PRP), recent study showed oxygen-rich PRP (ozonized PRP) have better therapeutic effects on bone and joint diseases. PRP injection has been widely used in the treatment of facial rejuvenation, but the efficacy of sufficient oxygen-rich PRP in facial rejuvenation has not been studied. Objective: Firstly, we examined whether ozone treatment can increase the concentration of GFs of PRP in vitro. And then a variety of subjective and objective detection methods were used to evaluate the effect of sufficient(10-12 mL each time for the injection of face and neck) oxygen-rich (ozonized PRP) PRP injection in facial rejuvenation by follow-up for 6 months. At last, we investigated the satisfaction, side effects and pain score of the treatment through a questionnaire survey. Methods: The concentration of main GFs in PRP treated with different dose of ozone in vitro was measured by ELISA. Clinical picture, the collagen thickness of dermis by reflectance confocal microscope(RCM), skin conditions (including spots, ultraviolet (UV) spots, brown spots, red area, pores, wrinkles, texture and porphyrin) by VISIA were collected before treatment and each month follow-up visit after treatment until 6-month follow-up period was finished. Patients' satisfaction, side effects and pain score were collected at the end of follow-up period. Results: PRP treated by high-dose ozone (57 µg/mL, ozone/PRP volume ratio:1/1) in vitro showed a significant increase in endothelial growth factor (EGF) and transforming growth factor-ß (TGF-ß) compared to baseline(P < 0.05). Collagen thickness of forehead, cheek and neck improved significantly compare to the baseline until to the 6 months after treatment. Spots, UV spots, brown spots, red area and texture improved significantly compare to the baseline(P < 0.05). All of participants reported improvement and have a median pain score of 4.19. No serious adverse events were observed. Conclusions: Ozone treatment can increase the concentration of GFs such as EGF and TGF-ß in PRP in vitro. Sufficient oxygen-rich PRP injection may be an effective and promising method to treat facial rejuvenation.