Disulfidptosis, a newly recognized cell death triggered by disulfide stress, has garnered attention for its potential role in osteoporosis (OP) pathogenesis. Although sulfide-related proteins are reported to regulate the balance of bone metabolism in OP, the precise involvement of disulfidptosis regulators remains elusive. Herein, leveraging the GSE56815 dataset, we conducted an analysis to delineate disulfidptosis-associated diagnostic clusters and immune landscapes in OP. Subsequently, vertebral bone tissues obtained from OP patients and controls were subjected to RNA sequencing (RNA-seq) for the validation of key disulfidptosis gene expression. Our analysis unveiled seven significant disulfidptosis regulators, including FLNA, ACTB, PRDX1, SLC7A11, NUBPL, OXSM, and RAC1, distinguishing OP samples from controls. Furthermore, employing a random forest model, we identified four diagnostic disulfidptosis regulators including FLNA, SLC7A11, NUBPL, and RAC1 potentially predictive of OP risk. A nomogram model integrating these four regulators was constructed and validated using the GSE35956 dataset, demonstrating promising utility in clinical decision-making, as affirmed by decision curve analysis. Subsequent consensus clustering analysis stratified OP samples into two different disulfidptosis subgroups (clusters A and B) using significant disulfidptosis regulators, with cluster B exhibiting higher disulfidptosis scores and implicating monocyte immunity, closely linked to osteoclastogenesis. Notably, RNA-seq analysis corroborated the expression patterns of two disulfidptosis modulators, PRDX1 and OXSM, consistent with bioinformatics predictions. Collectively, our study sheds light on disulfidptosis patterns, offering potential markers and immunotherapeutic avenues for future OP management.
ABSTRACT A subpopulation of neural crest termed the cardiac neural crest is required in avian embryos to initiate reorganization of the outflow tract of the developing cardiovascular system. In mammalian embryos, it has not been previously experimentally possible to study the long-term fate of this population, although there is strong inference that a similar population exists and is perturbed in a number of genetic and teratogenic contexts. We have employed a two-component genetic system based on Cre/lox recombination to label indelibly the entire mouse neural crest population at the time of its formation, and to detect it at any time thereafter. Labeled cells are detected throughout gestation and in postnatal stages in major tissues that are known or predicted to be derived from neural crest. Labeling is highly specific and highly efficient. In the region of the heart, neural-crest-derived cells surround the pharyngeal arch arteries from the time of their formation and undergo an altered distribution coincident with the reorganization of these vessels. Labeled cells populate the aorticopulmonary septum and conotruncal cushions prior to and during overt septation of the outflow tract, and surround the thymus and thyroid as these organs form. Neural-crest-derived mesenchymal cells are abundantly distributed in midgestation (E9.5-12.5), and adult derivatives of the third, fourth and sixth pharyngeal arch arteries retain a substantial contribution of labeled cells. However, the population of neural-crest-derived cells that infiltrates the conotruncus and which surrounds the noncardiac pharyngeal organs is either overgrown or selectively eliminated as development proceeds, resulting for these tissues in a modest to marginal contribution in late fetal and postnatal life.
Glioblastoma (GBM) is highly malignant and grows rapidly, and there is currently a lack of effective treatments. Metabolism provides the basis for the occurrence and development of GBM. Pyruvate dehydrogenase A1 (PDHA1) is a key component in both the tricarboxylic acid cycle and glycolysis, playing an important role in the metabolic processes related to cancer, but its role in GBM remains unclear. Glioma associated mesenchymal stem cells (GaMSC) play a significant role in the development of glioma. This study aims to explore the relationship between GaMSC derived exosomes (GAMSC-EXO) and PDHA1, as well as the effects and mechanisms on GBM glucose metabolism. In this study, human GaMSC-derived exosomes were isolated and identified. The role of GAMSC-EXO in GBM proliferation, migration, invasion and glucose metabolism was investigated. The upstream miRNA of PDHA1 was predicted and the relationship between miR-21-5p and PDHA1 in GAMSC-EXO and its effect on GBM glucose metabolism was investigated. We found that GAMSCs promote GBM cell proliferation, migration, invasion and glycolysis by releasing exosomes. After inhibiting GBM glycolysis, GBM proliferation, migration and invasion abilities were weakened. MiR-21-5p in exosomes was identified as the miRNA that affects the above biological behaviors. Mechanismly, miR-21-5p directly binds to the mRNA of PDHA1 and downregulates its transcription, thereby promoting GBM glycolysis. Together, this study demonstrated that exosomal miR-21-5p from GAMSC promoted GBM proliferation, migration, invasion, and glycolysis by targeting PDHA1, which provided novel insights into the metabolic interactions between GAMSCs and GBM cells, emphasizing the importance of exosome-mediated communication in tumor progression.
To compare the clinical efficacy and safety between percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fracture (OVCF) with intravertebral vacuum cleft (IVC).Between January 2010 and December 2013, 68 patients with single OVCF and IVC were treated, and the clinical data were retrospectively analyzed. Of 68 patients, 48 underwent PVP (PVP group) and 20 underwent PKP (PKP group). There was no significant difference in age, gender, disease duration, fracture level, bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI), and preoperative radiological parameters between 2 groups (P>0.05). The intraoperative incidence of cement leakage, cement volume, and operative time were compared between 2 groups; VAS score was used for evaluation of back pain and ODI for evaluation of dysfunction; the incidence of adjacent vertebral fracture was observed within 2 years. The vertebral height and kyphotic angle were measured on X-ray films; the rate of vertebral compression (CR), reduction rate (RR), progressive height loss (PHL), reduction angle (RA), and progressive angle (PA) were calculated.There was no significant difference in cement volume and the incidence of cement leakage between 2 groups (P>0.05). The operative time in PVP group was shorter than that in PKP group, showing significant difference (t=-8.821, P=0.000). The mean follow-up time was 2.4 years (range, 2.0-3.1 years). The VAS scores and ODI were significantly reduced at 1 day, 1 year, and 2 years after operation when compared with preoperative scores (P<0.05), but there was no significant difference between different time points after operation in 2 groups (P>0.05). Adjacent vertebral fracture occurred in 5 cases (10.4%) of PVP group and in 2 cases (10.0%) of PKP group, showing no significant difference (χ2=0.003, P=0.963). BMD was significantly increased at 1 year and 2 years after operation when compared with preoperative BMD (P<0.05), but no significant difference was found between 2 groups (t=0.463, P=0.642; t=0.465, P=0.646). The X-ray films showed that CR and kyphotic angle were significantly restored at immediate after operation in 2 groups (P<0.05); but vertebral height and kyphotic angle gradually aggravated with time, showing significant difference between at immediate and at 1 and 2 years after operation (P<0.05); there was no significant difference in CR and kyphotic angle between 2 groups at each time point (P>0.05). RR, RA, PHL, and PA showed no significant difference between 2 groups (P>0.05).There is similar clinical and radiological efficacy between PVP and PKP for treatment of OVCF with IVC. Re-collapse could happen after operation, so strict observation and follow-up are needed.比较经皮椎体成形术（percutaneous vertebroplasty,PVP）和经皮椎体后凸成形术（percutaneous kyphoplasty,PKP）治疗伴椎体内真空裂隙（intravertebral vacuum cleft,IVC）的骨质疏松椎体压缩骨折（osteoporotic vertebral compression fracture,OVCF）疗效。.回顾分析2010年1月－2013年12月，行PVP或PKP治疗并符合选择标准的68例伴IVC的OVCF患者临床资料。其中48例行PVP治疗（PVP组），20例行PKP治疗（PKP组）。两组患者性别、年龄、病程、损伤节段、骨密度以及术前背部疼痛视觉模拟评分（VAS）、Oswestry功能障碍指数（ODI）、影像学测量指标等一般资料比较，差异均无统计学意义（P＞0.05），具有可比性。比较两组术中骨水泥渗漏率、骨水泥注入量、手术时间，采用VAS评分评价背部疼痛程度，ODI评价功能障碍严重程度，2年内邻椎再骨折率。手术前后摄正侧位X线片，测量伤椎椎体高度及后凸角，并计算椎体压缩率（rate of vertebral compression,CR）、复位率（reduction rate,RR）、进展性高度丢失率（progressive height loss,PHL）、复位角度（reduction angle,RA）、进展性后凸角（progressive angle,PA）。.两组骨水泥注入量及骨水泥渗漏发生率比较，差异均无统计学意义（P＞0.05）；但PVP组手术时间较PKP组显著缩短（t=—8.821，P=0.000）。术后患者均获随访，随访时间2.0~3.1年，平均2.4年。两组术后1 d、1年及2年VAS评分、ODI均较术前显著降低（P＜0.05）；术后各时间点间比较，差异无统计学意义（P＞0.05）。术后2年内，PVP组5例（10.4%）、PKP组2例（10.0%）发生邻椎骨折，骨折发生率比较差异无统计学意义（χ2=0.003，P=0.963）。术后1、2年两组骨密度均较术前显著改善（P＜0.05），但两组间比较差异无统计学意义（t=0.463，P=0.642；t=0.465，P=0.646）。X线片测量显示，两组CR及后凸角均获得明显矫正，术后即刻两指标与术前比较差异有统计学意义（P＜0.05）；但术后1、2年时与术后即刻比较，差异有统计学意义（P＜0.05）；术后各时间点两组间CR及后凸角比较，差异均无统计学意义（P＞0.05）。两组RR、RA、PHL、PA比较，差异均无统计学意义（P＞0.05）。.PVP及PKP治疗伴IVC的OVCF可获得相似疗效，术后均可能发生再塌陷及后凸畸形，因此需注意随访观察。.
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