Anti-inflammatory, antiosteoporotic, and bone protective effect of hydroxysafflor yellow A against glucocorticoid-induced osteoporosis in rats.

Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.

Circulating tumour DNA-Based molecular residual disease detection in resectable cancers: a systematic review and meta-analysis.

BACKGROUND: Circulating tumour DNA (ctDNA)-based molecular residual disease (MRD) detection technology has been widely used for recurrence evaluation, but there is no agreement on the efficacy of assessing recurrence and overall survival (OS) prognosis, as well as the sensitivity and specificity of landmark detection and longitudinal detection. METHODS: We systematically searched Pubmed, Embase, Cochrane, and Scopus for prospective studies or randomized controlled trials that collected blood samples prospectively. The search period was from Jan 1, 2013, to Sept 10, 2023. We excluded retrospective studies. The primary endpoint was to assess the hazard ratio (HR) between circulating tumour DNA positive (ctDNA+) and negative (ctDNA-) for recurrence-free survival incidence (RFS), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), time to recurrence (TTR), distant metastasis-free survival (DMFS) or OS in patients with resectable cancers. We calculated the pooled HR of recurrence and OS and 95% confidence interval (CI) in patients with resected cancers using a random-effects model. Pooled sensitivity and specificity were estimated using the bivariate random effects model. FINDINGS: This systematic review and meta-analysis returned 7578 records, yielding 80 included studies after exclusion. We found that the HR of recurrence across all included cancers between patients with ctDNA+ and ctDNA- was 7.48 (95% CI 6.39-8.77), and the OS was 5.58 (95% CI 4.17-7.48). We also found that the sensitivity, area under the summary receiver operating characteristic curve (AUSROC) and diagnostic odds ratio (DOR) of longitudinal tests were higher than that of landmark tests between patients with ctDNA+ and ctDNA- (0.74, 95% CI 0.68-0.80 vs 0.50, 95% CI 0.46-0.55; 0.88 vs. 0.80; 25.70, 95% CI 13.20-45.40 vs. 9.90, 95% CI 7.77-12.40). INTERPRETATION: Postoperative ctDNA testing was a significant prognosis factor for recurrence and OS in patients with resectable cancers. However, the overall sensitivity of ctDNA-MRD detection could be better. Longitudinal monitoring can improve the sensitivity, AUSROC, and DOR. FUNDING: Special fund project for clinical research of Qingyuan People's Hospital (QYRYCRC2023006), plan on enhancing scientific research in GMU (GZMU-SH-301).

A novel biplanar positioning technique to guide iliosacral screw insertion: a retrospective study.

PURPOSE: To evaluate the safety and benefits of the biplanar position technique on operative time, radiation exposure, and screw placement accuracy. METHODS: In this study, we retrospectively evaluated the records of 64 patients with pelvic fractures (Tile B and C) between October 2020 and September 2021. According to the surgical methods selected by the patients, the patients were divided into a biplanar positioning technique group (biplanar group), a Ti-robot navigation group (Ti-robot group), and a traditional fluoroscopy-guided technique group (traditional group). Length of operation, blood loss, intra-operative radiation exposure fracture reduction, and the quality of screw positioning were compared among the three groups. RESULTS: One hundred three screws were implanted in 64 patients (biplanar group 22, Ti-robot group 21, traditional group 21). The average operation time was significantly less in the biplanar group (26.32 ± 6.32 min) than in the traditional group (79.24 ± 11.31 min), but significantly more than in the Ti-robot group (15.81 ± 3.9 min). The radiation exposure was similar in the biplanar group (740.53 ± 185.91 cGy/cm2) and Ti-robot group (678.44 ± 127.16 cGy/cm2), both of which were significantly more than in the traditional group (2034.58 ± 494.54 cGy/cm2). The intra-operative blooding loss was similar in the biplanar group (12.76 ± 3.77 mL) and the Ti-robot group (11.92 ± 4.67 mL), both of which were significantly less than in the traditional group (29.7 ± 8.01 mL). The Screw perforation was slightly lower in the biplanar group (94.1%) than in the Ti-robot group (97.2%) but was significantly higher than in the traditional group (75.7%). CONCLUSIONS: The biplanar positioning technique is as accurate and safe as computer-navigated systems for percutaneous iliosacral screw insertion, associated with shorter surgical time, lower intra-operative radiation exposure, and more accuracy compared to traditional fluoroscopy.

LINC01119 negatively regulates osteogenic differentiation of mesenchymal stem cells via the Wnt pathway by targeting FZD4.

BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into diverse cell types under specific conditions. Dysfunction in the osteogenic differentiation of MSCs can result in bone metabolism-related diseases, including osteoporosis. Accumulating evidence has revealed that long non-coding RNA (lncRNAs) play critical regulatory roles during MSC differentiation. METHODS: In the present study, we identified an evolutionarily conserved lncRNA expressed during the osteogenic differentiation of MSCs, which we termed LINC01119. We first identified LINC01119 as a negative regulator of the osteogenic differentiation of MSCs. RESULTS: LINC01119 knockdown markedly induced calcium deposition in bone marrow MSCs and promoted the osteogenic differentiation of MSCs. More importantly, we demonstrated the underlying molecular basis through which LINC01119 regulates osteogenesis via the Wnt pathway by targeting FZD4. Furthermore, we observed that transcription factor EBF3 could directly bind the promoter site of LINC01119. CONCLUSIONS: We first explored the molecular regulatory mechanism of LINC01119 during the osteogenic differentiation of MSCs and revealed that LINC01119 negatively regulates osteogenesis through the Wnt pathway by targeting FZD4.

The effect of bone morphogenetic protein 2 composite materials combined with cannulated screws in treatment of acute displaced femoral neck fractures.

The risk of avascular necrosis (AVN) and nonunion after treatment of displaced femoral neck fractures is increased in patients aged <60 years. Therefore we established a new protocol for closed reduction and internal fixation (CRIF) using cannulated screws combined with bone morphogenetic protein 2 (BMP-2) composite materials to treat acute femoral neck fractures.This study enrolled 78 patients with acute femoral neck fractures between April 2014 and September 2016. We treated 46 patients with a mean age of 43.8 years in study group. These patients were treated by CRIF combined with BMP-2 composite materials. In control group, there were 32 patients with a mean age of 42.09 years. The patients were treated by CRIF without BMP-2. The duration between presentation and surgery, operative time, Harris score and complications were recorded.In study group, 43 patients were followed up with an average of 31.3 months. One patient suffered nonunion and three patients presented AVN. In control group, 28 patients were followed up with an average of 32.3 months, the rate of AVN and fracture nonunion were 25% (7/28) and 21.4% (6/28) respectively, significantly higher than those in study group (P < .05).Acute displaced femoral neck fractures can be treated with CRIF and BMP-2 composite materials in a minimally invasive manner. This technique was reproducible and had fewer complications.

miR-129 inhibits tumor growth and potentiates chemosensitivity of neuroblastoma by targeting MYO10.

Although the treatment strategies for neuroblastoma (NB) develop rapidly, a considerable number of patients could not benefit from chemotherapy. Here, we revealed a miR-129-MYO10 axis that regulated neuroblastoma growth and chemosensitivity. Mechanistically, MYO10 was up-regulated in neuroblastoma tissues and associated with poor overall survival. While overexpression of MYO10 enhanced tumor growth, genetic inhibition of MYO10 led to growth-inhibitory and chemopotentiating effects in neuroblastoma. MYO10 was further identified as a target of miR-129. Our data showed that miR-129 down-regulated MYO10 expression and subsequently suppressed cell growth. Re-expression of MYO10 significantly rescued miR129-mediated proliferation repression and chemosensitivity. In conclusion, our results demonstrated that miR-129 inhibited neuroblastoma growth and potentiated chemosensitivity by targeting MYO10, which may represent promising targets and rational therapeutic options for neuroblastoma.

MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2.

Osteosarcoma is the most common type of bone cancer, especially in children and young adults. Recently, long noncoding RNAs (lncRNAs) have emerged as new prognostic markers and gene regulators in several cancers, including osteosarcoma. In this study, we investigated the contributions of the lncRNA MALAT1 in osteosarcoma with a specific focus on its transcriptional regulation and its interaction with EZH2. Our results showed that MALAT1 was significantly increased in osteosarcoma specimens and cell lines. ROC curve analysis showed that MALAT1 had a higher area under the curve than alkaline phosphatase, and Kaplan-Meier survival analysis indicated that patients with high serum levels of MALAT1 showed reduced survival rate. Knockdown of MALAT1 decreased osteosarcoma cell invasion and promoted E-cadherin expression. Mechanistic investigations showed that MALAT1 was transcriptionally activated by TGF-ß. Additionally, EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in osteosarcoma, and this association finally suppressed the expression of E-cadherin. Subsequently, our gain and loss function assay showed that MALAT1 overexpression promoted cell metastasis and decreased E-cadherin level, however, this effect was partially reversed by EZH2 knockdown. In conclusion, our work illuminates that lncRNA MALAT1 is a potential diagnostic and prognostic factor in osteosarcoma and further demonstrates how MALAT1 confers an oncogenic function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.

Long noncoding RNA MALAT1 promotes cell proliferation through suppressing miR-205 and promoting SMAD4 expression in osteosarcoma.

Increasing evidences have indicated that long non-coding RNAs (lncRNAs) play an important role in multiply biological processes including cell development, differentiation, proliferation and invasion. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), is a highly conserved nuclear ncRNA and a key regulator of metastasis development in several cancers. However, its role in osteosarcoma progression is not well known. In this study, we sought to determine the clinical and bilogical role of MALAT1 in osteosarcoma progression. RT-qPCR analysis showed that MALAT1 expression was significantly increased in primary osteosarcoma tissues and cell lines. Kaplan-Meier analysis indicated that patients with high expression of MALAT1 was associated with poor overall survival compared with the low expressing patients. Furthermore, the gain and loss function assay showed that miR-205 was suppressed by MALAT1 in osteosarcoma and this interaction between miR-205 and MALAT1 has reciprocal effects. Cell viability assay showed that MALAT1 promoted MG-63 and SAOS-2 cell growth through suppressing miR-205. Subsequently, the downstream gene SMAD4 was identified as a direct functional target of miR-205, and miR-205 suppressed osteosarcoma cell growth through suppressing SMAD4. Finally, we demonstrated that MALAT1 promoted osteosarcoma progression via a miR-205-SMAD4 axis. In conclusion, we revealed that enhanced MALAT1 expression predicted unfavourable outcome in osteosarcoma and promoted cell proliferation through suppressing miR-205 and activating SMAD4 function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.