Pluripotent stem cell-derived CTLs targeting FGFR3-TACC3 fusion gene in osteosarcoma.

Osteosarcoma, a highly aggressive bone cancer, poses significant treatment challenges. This study investigates a novel approach utilizing induced pluripotent stem cells (iPSCs) engineered with the FGFR3-TACC3 fusion gene to generate cytotoxic T lymphocytes (CTLs) targeting osteosarcoma. The aim was to assess the efficacy of iPSC-derived CTLs in combating osteosarcoma progression. Abnormal expression of the FGFR3-TACC3 fusion gene was confirmed in osteosarcoma samples. iPSCs were successfully modified to express the fusion gene and were then differentiated into CTLs. In vitro experiments demonstrated that these modified CTLs effectively killed osteosarcoma cells, induced apoptosis, and inhibited migration and invasion. Findings were validated in in vivo experiments. This study suggests that iPSC-derived CTLs targeting FGFR3-TACC3 hold promise for personalized immunotherapy against osteosarcoma.

Application of Intraoperative Individualized Cup Combination-Cup-on-Cup Technique in Severe Acetabular Defects.

This study aimed to investigate the application of the cup-on-cup technique in revision total hip arthroplasty (THA) and report clinical and radiographic outcomes from a series of case follow-ups. Retrospective analysis of 10 patients who underwent acetabular prosthesis revision with cup-on-cup technique. According to the Paprosky classification of acetabular bone defects, there were 2 cases of type II C, 3 cases of type III A, and 5 cases of type III B. The average follow-up was 54.8 ± 5.1 months, and the Harris score of the hip joint increased from 37.0 ± 9.9 preoperatively to 80.5 ± 3.1 postoperatively at the final follow-up (p < 0.001). Comparing the surgical side's hip center of rotation (COR) to the contralateral side, the preoperative average upward displacement was 33.8 ± 15.0 mm, while the postoperative average upward displacement was 0.2 ± 3.3 mm (p < 0.001). Similarly, the preoperative average inward displacement was 9.1 ± 5.1 mm, while the postoperative average outward displacement was 1.8 ± 1.6 mm (p < 0.001). There was no significant difference (p = 0.71) between the average density values of the contralateral and surgical sides at the final follow-up, which were 127.4 ± 13.7 and 125.0 ± 14.8, respectively. During the follow-up period, all patients achieved satisfactory radiographic outcomes, and no prosthetic loosening was observed. The cup-on-cup technique can reconstruct acetabular bone defects and restore hip COR in revision THA, with favorable clinical and radiographic outcomes.

Integrated single-cell and bulk RNA sequencing identifies POSTN as a potential biomarker and therapeutic target for rheumatoid arthritis.

BACKGROUND: This study aimed to integrate single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to identify potential biomarkers and therapeutic targets for rheumatoid arthritis (RA). METHOD: Firstly, we obtained the synovial scRNA-seq data from the Immport database and bulk RNA-seq data from the Gene Expression Omnibus (GEO) database. Then, we used weighted gene correlation network analysis (WGCNA) to screen for module genes most relevant to RA and intersected them with the differentially expressed genes (DEGs) obtained from scRNA-seq and bulk RNA-seq to obtain intersecting genes. Next, we constructed a protein-protein interaction (PPI) network of hub genes using the STRING database and Cytoscape software and validated its expression using external validation cohorts. Finally, we performed immune cell infiltration analysis using CIBERSORT and explored the expression and drug binding activity of key gene using clinical samples and molecular docking, respectively. RESULT: We identified six cellular subgroups through dimensionality reduction and clustering, and fibroblasts may be the most important cell cluster in RA based on pseudotime and cell-cell communication analyses. Subsequently, we intersected module genes with DEGs obtained from scRNA-seq and bulk RNA-seq and constructed a PPI network of hub genes (BGN, COL11A1, COL1A1, GUCY1A1, POSTN). In external validation cohorts, POSTN was highly expressed and demonstrated the highest diagnostic performance (AUC = 0.716). In subsequent analyses, we defined POSTN as a key gene and found that its expression level was positively correlated with M2 macrophages in immune cell infiltration analysis. Additionally, POSTN was upregulated in clinical samples and exhibited favorable binding activity with nine anti-rheumatoid arthritis drugs (affinity ≤ -6.0 kcal/mol). CONCLUSION: Through bioinformatics analysis, clinical sample validation, and molecular docking, we found that POSTN was highly expressed in RA and stably bound to common anti-rheumatoid arthritis drugs, which will provide new insights into potential biomarkers and therapeutic targets for RA.

Double Superconducting Dome of Quasi Two-Dimensional TaS2 in Non-Centrosymmetric van der Waals Heterostructure.

Two-dimensional van der Waals heterostructures (2D-vdWHs) based on transition metal dichalcogenides (TMDs) provide unparalleled control over electronic properties. However, the interlayer coupling is challenged by the interfacial misalignment and defects, which hinders a comprehensive understanding of the intertwined electronic orders, especially superconductivity and charge density wave (CDW). Here, by using pressure to regulate the interlayer coupling of non-centrosymmetric 6R-TaS2 vdWHs, we observe an unprecedented phase diagram in TMDs. This phase diagram encompasses successive suppression of the original CDW states from alternating H-layer and T-layer configurations, the emergence and disappearance of a new CDW-like state, and a double superconducting dome induced by different interlayer coupling effects. These results not only illuminate the crucial role of interlayer coupling in shaping the complex phase diagram of TMD systems but also pave a new avenue for the creation of a novel family of bulk heterostructures with customized 2D properties.

Reliability and accuracy of intraoperative fluoroscopy assessment of acetabular cup anteversion in supine direct anterior approach total hip arthroplasty.

Poor implantation positioning of hip prostheses is considered the primary factor affecting postoperative joint wear. Cup anteversion in direct anterior approach (DAA) total hip arthroplasty (THA) is often excessive. Intraoperative fluoroscopy (IF) are effective for improving implant placement accuracy. This study aimed to analyze IF's reliability and accuracy in assessing intraoperative anteversion. Sixty-two consecutive hips underwent primary THA utilizing DAA alongside IF for cup placement. Intraoperative anteversion was measured using IF images, while postoperative CT and standard anteroposterior (AP) radiographs were used to calculate true anteversion component angles. Differences and correlations between intraoperative and true anteversions were analyzed, and intraclass correlation coefficients (ICC) determined the inter- and intra-observer reliabilities. Excellent intra- and inter-observer reliabilities were observed for all radiographic and CT methods (ICC > 0.9). Strong correlations (PCC > 0.6) existed between anteversion measured on IF image and postoperative CT and AP pelvic measurements. Intraoperative anteversion measured on IF images (16.8 ± 3.2°) was smaller than anteversion measured postoperatively on AP X-rays (21.3 ± 4.7°, P < 0.001) and CT (22.0 ± 4.9°, P < 0.001), with average differences of 4.5°and 5.3°, respectively. Under several influencing factors, the accuracy of IF in assessing cup anteversion in DAA-THA may be limited. However, this still requires large-sample experiments for verification.

Glaucocalyxin A delays the progression of OA by inhibiting NF-κB and MAPK signaling pathways.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint condition marked by inflammation and cartilage breakdown. Currently, there is a dearth of treatment medications that can clearly slow the course of OA. Glaucocalyxin A (GLA) is a diterpene chemical identified and extracted from Rabdosia japonica with antithrombotic, anticoagulant, anti-tumor, anti-inflammatory, anti-oxidant, and other pharmacological properties. Previous research has linked inflammation to abnormalities in the homeostasis of the extracellular matrix (ECM). Although GLA has been shown to have anti-inflammatory qualities, its effects on the progression of OA are unknown. As a result, the goal of this study was to see if GLA could slow the course of OA. METHODS: ATDC5 cells were stimulated by IL-1ß to create an inflammatory chondrocyte damage model. Quantitative polymerase chain reaction, Western Blot, high-density culture, and immunofluorescence were used to detect the expression levels of associated gene phenotypes. We also created a mouse model of OA induced by destabilization of the medial meniscus (DMM) instability, and GLA was administered intraperitoneally once every two days for eight weeks. Mice knee specimens were stained with hematoxylin-eosin, Safranin O/fast green, and immunohistochemical, and the Osteoarthritis Research Society International grade system and Mankin's score were used to assess the protective effect of GLA on cartilage. RESULTS: In vitro and in vivo, we explored the effects and molecular processes of GLA as a therapy for OA. The findings demonstrated that GLA might reduce the expression of associated inflammatory mediators and protect the ECM by inhibiting the NF-κB and MAPK signaling pathways. Animal research revealed that GLA could protect against the DMM-induced OA model mice by stabilizing ECM. CONCLUSION: Taken together, our findings show that GLA has a protective impact on cartilage throughout OA progression, implying that GLA could be employed as a possible therapeutic agent for OA, thus giving a new therapeutic method for the treatment of OA.

Perimeter monitoring of urban buried pipeline threated by construction activities based on distributed fiber optic sensing and real-time object detection.

Urban construction activities seriously jeopardize the security of buried pipeline. Distributed optical fiber vibration monitoring is one of the most promising ways to prevent third-party threats, of which the biggest challenge is to quickly and accurately detect rare abnormal events from extremely large amounts of time-space raw data. By analogy with image recognition, the task here is similar to object detection if considering the time-space optical signals as the grayscale images and the abnormal events as the objects. Given this, what we believe to be a novel monitoring method is proposed, which consists of two Faster R-CNN models, a max pooling layer and a monitoring strategy. In the field tests, the 86-hour optical vibration signals for 5.25 km distance are recognized within 6.6 minutes with the recognition rate of 98.85% for construction activities, and only two false alarms are issued. The proposed method can reduce the recognition time by 99.59% compared to the CNN-based method.

The TGFß1/SMADs/Snail1 signaling axis mediates pericyte-derived fibrous scar formation after spinal cord injury.

AIMS: The deposition of fibrous scars after spinal cord injury (SCI) affects axon regeneration and the recovery of sensorimotor function. It has been reported that microvascular pericytes in the neurovascular unit are the main source of myofibroblasts after SCI, but the specific molecular targets that regulate pericyte participation in the formation of fibrous scars remain to be clarified. METHODS: In this study, a rat model of spinal cord dorsal hemisection injury was used. After SCI, epigallocatechin gallate (EGCG) was intraperitoneally injected to block the TGFß1 signaling pathway or LV-Snail1-shRNA was immediately injected near the core of the injury using a microsyringe to silence Snail1 expression. Western blotting and RT-qPCR were used to analyze protein expression and transcription levels in tissues. Nissl staining and immunofluorescence analysis were used to analyze neuronal cell viability, scar tissue, and axon regeneration after SCI. Finally, the recovery of hind limb function after SCI was evaluated. RESULTS: The results showed that targeted inhibition of Snail1 could block TGFß1-induced pericyte-myofibroblast differentiation in vitro. In vivo experiments showed that timely blockade of Snail1 could reduce fibrous scar deposition after SCI, promote axon regeneration, improve neuronal survival, and facilitate the recovery of lower limb motor function. CONCLUSION: In summary, Snail1 promotes the deposition of fibrous scars and inhibits axonal regeneration after SCI by inducing the differentiation of pericytes into myofibroblasts. Snail1 may be a promising therapeutic target for SCI.

Mechanism of lysine oxidase-like 1 promoting synovial inflammation mediating rheumatoid arthritis development.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that causes great distress to patients and society. Early diagnosis is the key to the successful treatment of RA. The basement membrane, one of the oldest tissue structures, is localized under the epithelium. Its complex composition and rich biological functions have made it a focus of research in recent years, while basement membrane-associated genetic variants are involved in most human disease processes. The aim of this study is to find new diagnostic biomarkers for RA and explore their role and possible mechanism in rheumatoid arthritis. The GSE12021, GSE55235 and GSE55457 datasets were downloaded from the GEO database. Their fraction associated with basement membrane genes was analyzed and differentially expressed genes between the disease and normal groups were explored. We identified two basement membrane-associated genes, lysine oxidase-like 1 (LOXL1) and discoid peptide receptor 2 (DDR2). Focusing on the more interesting LOXL1, we found that LOXL1 expression was significantly elevated in the synovium of patients with rheumatoid arthritis, and LOXL1 mRNA and protein levels were elevated in tumor necrosis factor α-stimulated human synovial sarcoma cells (SW982). And LOXL1 knockdown inhibited tumor necrosis factor α-induced inhibition in SW982 cells expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX2), and interleukin-6 (IL-6). Interestingly, knockdown of LOXL1 inhibited the phosphorylation of PI3K and AKT. In summary, LOXL1 may become a novel diagnostic gene for RA, and knockdown of LoxL1 may inhibit synovial inflammation by affecting PI3K/AKT pathway.

Development and validation of multiple linear regression models for predicting total hip arthroplasty acetabular prosthesis.

PURPOSE: To establish a multivariate linear equation to predict the diameter (outer diameter) of the acetabular prosthesis used in total hip arthroplasty. METHODS: A cohort of 258 individuals who underwent THA at our medical facility were included in this study. The independent variables encompassed the patients' height, weight, foot length, gender, age, and surgical access. The dependent variable in this study was the diameter of the acetabular prosthesis utilized during the surgical procedure. The entire cohort dataset was randomly partitioned into a training cohort and a validation cohort, with a ratio of 7:3, employing the SPSS 26.0 software. Pearson correlation analysis was conducted to examine the relationships between the patients' height, weight, foot length, gender, age, surgical access, and the diameter of the acetabular prosthesis in the training cohort. Additionally, a multiple linear regression equation was developed using the independent variables from the training cohort and the diameter of the acetabular prosthesis as the dependent variable. This equation aimed to predict the diameter of the acetabular prosthesis based on the patients' characteristics. The accuracy of the equation was evaluated by substituting the data of the validation cohort into the multiple linear equation. The predicted acetabular prosthesis diameters were then compared with the actual diameters used in the operation. RESULTS: The correlation analysis conducted on the training cohort revealed that surgical access (r = 0.054) and age (r = -0.120) exhibited no significant correlation with the diameter of the acetabular prosthesis utilized during the intraoperative procedure. Conversely, height (r = 0.687), weight (r = 0.654), foot length (r = 0.687), and sex (r = 0.354) demonstrated a significant correlation with the diameter of the acetabular prosthesis used intraoperatively. Furthermore, a predictive equation, denoted as Y (acetabular prosthesis diameter in mm) = 20.592 + 0.548 × foot length (cm) + 0.083 × height (cm) + 0.077 × weight (kg), was derived. This equation accurately predicted the diameter within one size with an accuracy rate of 64.94% and within two sizes with an accuracy rate of 94.81%. CONCLUSION: Anthropometric data can accurately predict the diameter of acetabular prosthesis during total hip arthroplasty.

ADRM1/RPN13 attenuates cartilage extracellular matrix degradation via enhancing UCH37-mediated ALK5 deubiquitination.

Osteoarthritis (OA) is the most common age-related joint disorder with no effective therapy, and its specific pathological mechanism remains to be fully clarified. Adhesion-regulating molecule 1 (ADRM1) has been proven to be involved in OA progression as a favorable gene. However, the exact mechanism of ADRM1 involved in OA were unknown. Here, we showed that the ADRM1 expression decreased in human OA cartilage, destabilization of the medial meniscus (DMM)-induced mouse OA cartilage, and interleukin (IL)-1ß-induced primary mouse articular chondrocytes. Global knockout (KO) ADRM1 in cartilage or ADRM1 inhibitor (RA190) could accelerate the disorders of extracellular matrix (ECM) homeostasis, thereby accelerated DMM-induced cartilage degeneration, whereas overexpression of ADRM1 protected mice from DMM-induced OA development by maintaining the homeostasis of articular cartilage. The molecular mechanism study revealed that ADRM1 could upregulate ubiquitin carboxy-terminal hydrolase 37 (UCH37) expression and bind to UCH37 to activate its deubiquitination activity. Subsequently, increased and activated UCH37 enhanced activin receptor-like kinase 5 (ALK5) deubiquitination to stabilize ALK5 expression, thereby maintaining ECM homeostasis and attenuating cartilage degeneration. These findings indicated that ADRM1 could attenuate cartilage degeneration via enhancing UCH37-mediated ALK5 deubiquitination. Overexpression of ADRM1 in OA cartilage may provide a promising OA therapeutic strategy.

Identification of several inflammation-related genes based on bioinformatics and experiments.

BACKGROUND: Osteoarthritis (OA) is a common disease of elderly individuals, with an unclear pathogenesis and limited treatment options to date. Inflammation occurs prominently in osteoarthritis, thereby making anti-inflammatory treatments promising in clinical outcomes. Therefore, it is of diagnostic and therapeutic significance to explore more inflammatory genes. METHOD: In this study, appropriate datasets were first acquired through gene set enrichment analysis (GSEA), followed by inflammation-related genes through weighted gene coexpression network analysis (WGCNA). Two machine learning algorithms (random forest-RF and support vector machine-recursive feature elimination, SVM-RFE) were used to capture the hub genes. In addition, two genes negatively associated with inflammation and osteoarthritis were identified. Afterwards, these genes were verified through experiments and network pharmacology. Due to the association between inflammation and many diseases, the expression levels of the above genes in various inflammatory diseases were determined through literature and experiments. RESULT: Two hub genes closely related to osteoarthritis and inflammation were obtained, namely, lysyl oxidase-like 1 (LOXL1) and pituitary tumour-transforming gene (PTTG1), which were shown to be highly expressed in osteoarthritis according to the literature and experiments. However, the expression levels of receptor expression-enhancing protein (REEP5) and cell division cycle protein 14B (CDC14B) remained unchanged in osteoarthritis. This finding was consistent with our verification from the literature and experiments that some genes were highly expressed in numerous inflammation-related diseases, while REEP5 and CDC14B were almost unchanged. Meanwhile, taking PTTG1 as an example, we found that inhibition of PTTG1 expression could suppress the expression of inflammatory factors and protect the extracellular matrix through the microtubule-associated protein kinase (MAPK) signalling pathway. CONCLUSIONS: LOXL1 and PTTG1 were highly expressed in some inflammation-related diseases, while that of REEP5 and CDC14B were almost unchanged. PTTG1 may be a potential target for the treatment of osteoarthritis.

Secoisolariciresinol diglucoside Ameliorates Osteoarthritis via Nuclear factor-erythroid 2-related factor-2/ nuclear factor kappa B Pathway: In vitro and in vivo experiments.

Osteoarthritis (OA) is an age-related joint disease in which inflammation and extracellular matrix (ECM) degradation play a crucial role in the destruction of articular cartilage. Secoisolariciresinol diglucoside (SDG), the main lignan in wholegrain flaxseed, which has been reported to remarkably suppress inflammation and oxidative stress, may have potential therapeutic value in OA. In this study, the effect and mechanism of SDG against cartilage degeneration were verified in the destabilization of the medial meniscus (DMM) and collagen-induced (CIA) arthritis models and interleukin-1ß (IL-1ß)-stimulated osteoarthritis chondrocyte models. From our experiments, SDG treatment downregulated the expression of pro-inflammatory factors induced by IL-1ß in vitro, including inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Additionally, SDG promoted the expression of collagen II (COL2A1) and SRY-related high-mobility-group-box gene 9(SOX9), while suppressing the expression of a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5) and matrix metalloproteinases 13(MMP13), which leads to catabolism. Consistently, in vivo, SDG has been identified to have chondroprotective effects in DMM-induced and collagen-induced arthritis models. Mechanistically, SDG exerted its anti-inflammation and anti-ECM degradation effects by activating the Nrf2/HO-1 pathway and inhibiting the nuclear factor kappa B (NF-κB) pathway. In conclusion, SDG ameliorates the progression of OA via the Nrf2/NF-κB pathway, which indicates that SDG may have therapeutic potential for OA.

Transoropharyngeal closed reduction for traumatic atlantoaxial dislocation: a novel technique for fast and precise reduction.

PURPOSE: The aim of this study is to introduce a new technique for the rapid and accurate reduction of traumatic atlantoaxial dislocation (TAAD) and to investigate its radiological and clinical outcomes. METHODS: The clinical outcomes of 18 patients who were diagnosed with acute TAAD and underwent rapid transoropharyngeal closed reduction in our hospital were retrospectively analyzed from January 2015 to December 2020. Following general anaesthesia, all patients were immediately treated with oropharyngeal reduction under somatosensory evoked potential monitoring. The Japanese Orthopedic Association score, neck disability index and visual analog scale score for neck pain were used to evaluate clinical efficacy. Atlantodental distance, posterior atlantodental interval, and the clivus-canal angle were used to assess reduction and spinal cord compression. RESULTS: The mean follow-up time was 23.3 months, with a range of 13-38 months. No neurovascular injury occurred during the operations. For all patients, the closed reduction method through the oropharynx under general anaesthesia was successful, and the success rate of reduction was 100%. All patients recovered uneventfully with marked improvement in clinical outcomes and imaging parameters (P < 0.01). Two patients developed mild postoperative dysphagia. One patient developed postoperative fever and pulmonary infection. CONCLUSION: Rapid trans-oropharyngeal closed reduction can safely, effectively, and rapidly reduce acute TAAD. This method provides a new strategy for treatment of the condition.

A comprehensive pan-cancer analysis unveiling the oncogenic effect of plant homeodomain finger protein 14 (PHF14) in human tumors.

The plant homeodomain (PHD) finger refers to a protein motif that plays a key role in the recognition and translation of histone modification marks by promoting gene transcriptional activation and silencing. As an important member of the PHD family, the plant homeodomain finger protein 14 (PHF14) affects the biological behavior of cells as a regulatory factor. Several emerging studies have demonstrated that PHF14 expression is closely associated with the development of some cancers, but there is still no feasible pan-cancer analysis. Based on existing datasets from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we performed a systematic analysis of the oncogenic role of the PHF14 gene in 33 human cancers. The expression level of PHF14 was significantly different between different types of tumors and adjacent normal tissues, and the expression or genetic alteration of PHF14 gene was closely related to the prognosis of most cancer patients. Levels of cancer-associated fibroblasts (CAFs) infiltration in various cancer types were also observed to correlate with PHF14 expression. In some tumors, PFH14 may play a role in tumor immunity by regulating the expression levels of immune checkpoint genes. In addition, the results of enrichment analysis showed that the main biological activities of PHF14 were related to various signaling pathways or chromatin complex effects. In conclusion, our pan-cancer research shows that the expression level of PHF14 is closely related to the carcinogenesis and prognosis of certain tumors, which needs to be further verified by more experiments and more in-depth mechanism exploration.

Modulating Charge-Density Wave Order and Superconductivity from Two Alternative Stacked Monolayers in a Bulk 4Hb-TaSe2 Heterostructure via Pressure.

Two-dimensional (2D) van der Waals heterostructures (VDWHs) containing a charge-density wave (CDW) and superconductivity (SC) have revealed rich tunability in their properties, which provide a new route for optimizing their novel exotic states. The interaction between SC and CDW is critical to its properties; however, understanding this interaction within VDWHs is very limited. A comprehensive in situ study and theoretical calculation on bulk 4Hb-TaSe2 VDWHs consisting of alternately stacking 1T-TaSe2 and 1H-TaSe2 monolayers are investigated under high pressure. Surprisingly, the superconductivity competes with the intralayer and adjacent-layer CDW order in 4Hb-TaSe2, which results in substantially and continually boosted superconductivity under compression. Upon total suppression of the CDW, the superconductivity in the individual layers responds differently to the charge transfer. Our results provide an excellent method to efficiently tune the interplay between SC and CDW in VDWHs and a new avenue for designing materials with tailored properties.

Surfactin suppresses osteoclastogenesis via the NF-κB signaling pathway, promotes osteogenic differentiation in vitro, and inhibits oestrogen deficiency-induced bone loss in vivo.

BACKGROUND: Fractures caused by osteoporosis (OP) are one of the main causes of death in the elderly, bringing a heavy burden to the country and society. The imbalance between osteoblast-mediated osteogenesis and osteoclast-mediated bone resorption is an important cause of OP. Therefore, finding drugs that can regulate this dynamic balance can be an important way to treat osteoporosis. Surfactin is a highly effective biosurfactant derived from Bacillus subtilis and it has been proven to have various pharmacological effects in previous studies, but its effect on bone metabolism remains unknown. Here, we performed a study on the role and mechanism of Surfactin in inhibiting osteoclastogenesis and its possible mechanism as well as the role in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: We investigated the effect of Surfactin on osteoclast differentiation and osteogenic differentiation in vitro and in vivo. The effect of Surfactin on the activity of osteoclastogenesis and osteogenesis was verified by CCK-8 assay, quantitative Real-time polymerase chain reaction (qPCR) and Western blotting analysis were used to verify the effect of Surfactin on osteoclast and osteogenic differentiation-specific genes and proteins. The effect of Surfactin on TRAP、ALP activity and mineral deposition was verified by TRAP、ALP and ARS staining. We then used an ovariectomy-induced osteoporosis mice model to observe the effect of Surfactin in vivo. RESULTS: Surfactin is noncytotoxic to BMMs, RAW264.7, and BMSCs. And it can effectively inhibit osteoclastogenesis and promote osteogenic differentiation. Moreover, we found that Surfactin can inhibit the differentiation of osteoclasts through the NF-κB signaling pathway. Surfactin can also alleviate bone loss in ovariectomy-induced osteoporosis mice. CONCLUSIONS: Our results suggest that Surfactin can inhibit osteoclastogenesis through the NF-κB signaling pathway, promote the osteogenic differentiation of BMSCs, and also can effectively alleviate bone loss in ovariectomy-induced osteoporosis mice.

lncRNA SERPINB9P1 Regulates SIRT6 Mediated Osteogenic Differentiation of BMSCs via miR-545-3p.

Evidence has shown that the altered osteogenic differentiation of human bone marrow stromal cells (BMSCs) under pathological conditions, such as osteoporosis, lead to the imbalance of bone tissue generation and destruction. Recent studies have indicated that long noncoding RNAs may play a role in regulating BMSCs osteogenic differentiation. This contributed to our impetus to move forward with the investigation of the function of lncRNA SERPINB9P1 in osteogenic differentiation of BMSCs and the potential mechanisms involved. Osteogenic differentiation of BMSCs was induced by osteogenic medium. Relative expression of lncRNA SERPINB9P1 and miR-545-3p were tested by qRT-PCR. Osteogenic mineralization was examined by Alizarin S Red staining, ALP staining, and ALP activity assay. Expression of osteoblastic markers were detected by Western blot. RNA-binding protein immunoprecipitation and dual-luciferase reporter assays were performed to test the interaction between lncRNA SERPINB9P1 and miR-545-3p. BMSCs osteogenic differentiation resulted in LncRNA SERPINB9P1 overexpression while miR-545-3p inhibition. Functional assays suggest that knockdown of lncRNA SERPINB9P1 or overexpression of miR-545-3p both inhibit BMSC osteogenic differentiation. lncRNA SERPINB9P1 was proven to regulate the osteogenic differentiation of BMSCs by altering SIRT6 expression through its suppressive effects on miR-545-3p. lncRNA SERPINB9P1 promotes osteogenic differentiation of BMSCs through the miR-545-3p/SIRT6 pathway.

Development and validation of a prognostic nomogram for bone metastasis from lung cancer: A large population-based study.

Background: Bone is one of the most common metastatic sites of advanced lung cancer, and the median survival time is significantly shorter than that of patients without metastasis. This study aimed to identify prognostic factors associated with survival and construct a practical nomogram to predict overall survival (OS) in lung cancer patients with bone metastasis (BM). Methods: We extracted the patients with BM from lung cancer between 2011 and 2015 from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate Cox regressions were performed to identify independent prognostic factors for OS. The variables screened by multivariate Cox regression analysis were used to construct the prognostic nomogram. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability. Results: A total of 7861 patients were included in this study and were randomly divided into training (n=5505) and validation (n=2356) cohorts using R software in a ratio of 7:3. Cox regression analysis showed that age, sex, race, grade, tumor size, histological type, T stage, N stage, surgery, brain metastasis, liver metastasis, chemotherapy and radiotherapy were independent prognostic factors for OS. The C-index was 0.723 (95% CI: 0.697-0.749) in the training cohorts and 0.738 (95% CI: 0.698-0.778) in the validation cohorts. The AUC of both the training cohorts and the validation cohorts at 3-month (0.842 vs 0.859), 6-month (0.793 vs 0.814), and 1-year (0.776 vs 0.788) showed good predictive performance, and the calibration curves also demonstrated the reliability and stability of the model. Conclusions: The nomogram associated with the prognosis of BM from lung cancer was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients.