Orientated-quantitative computed tomography study on individualized axial safety target area of femoral neck screw channel and establishment of a stable spatial coordinate system based on anterior cortex of femoral neck basilar.

BACKGROUND: Frequent in-out-in femoral neck screws were reported potential huge iatrogenic-injury risks, related to axial safe target area (ASTA) of femoral neck screws channel. However, orientated-quantitative ASTA based on stable coordinate system was unreported before. METHODS: Three-dimensional reconstruction was performed on computed tomography (CT) images of 139 intact normal hips, and the intersection area, defined as ASTA, was obtained by superimposing the axial CT images of each femoral neck. Taking anterior cortex of femoral neck basilar (AC-FNB) as landmark, a coordinate system was established to measure the anterior-posterior diameter (D-AP), the superior-inferior diameter (D-SI) and the oblique angle respectively. Each intersection was overlaid up to the axial CT images to determine the coronal location of the ASTA boundaries. RESULTS: Each ASTA presented an inclined rounded triangle with a flat anterior base coincided with AC-FNB. There were significant sex differences in D-SI (male: 33.6±2.3 vs. female: 29.4±1.9 mm) and D-AP (male: 25.3±2.1 vs. 21.9±1.9 mm), P <0.001. D-SI was found to be positively correlated with D-AP ( R2 =0.6). All fluoroscopic visible border isthmus completely matched the corresponding ASTA boundaries. The oblique angle was 5-53° (male: 28.1±10.3°, female: 27.1±8.2°) without significant difference between sexes. CONCLUSION: The intersection method was employed to conveniently acquire orientated-quantitative individualized ASTA. Under this coordinate system, x-ray data of screws could be converted to axial coordinates in CT ASTA, which could help surgeons design combined screws configuration preoperatively and evaluate quantitatively their axial position intraoperatively.

In-hospital waiting time to surgery and functional outcomes in geriatric hip fractures: a directed acyclic graph-based preplanned analysis from a prospective multicenter cohort study.

BACKGROUND: The early recovery of hip function after hip fracture surgery values more attention, especially for patients with delayed surgery of longer than 48 h. We aim to evaluate the associations of in-hospital surgical waiting time with the functional outcomes [Harris Hip Score (HHS), Parker Mobility Score (PMS), and EuroQol 5 dimensions VAS (visual analogue scale) score (EQ-5D VAS)] in elderly patients who sustained hip fractures. MATERIALS AND METHODS: Data on sociodemographic and clinical factors were prospectively collected using a multicenter hip fracture registry system. Participants in the cohort underwent a 12-month follow-up investigation. After adjusting potential confounders identified by the directed acyclic graphs, the associations between surgical waiting time longer than 48 h and functional outcomes were estimated by log-binomial regression and multivariable linear regression models with generalized estimating equations. RESULTS: Of 863 survival participants with available functional data at 12 months after surgery, an increased risk was obtained from receiving surgery after 48 h and the poor functional outcomes (HHS<80: relative risk (RR)=1.56, 95% CI: 1.00-2.51; PMS<7: RR=1.49, 95% CI: 1.13-2.01; EQ-5D VAS<80: RR=1.97, 95% CI: 1.57-2.47). In-hospital waiting time greater than 48 h were time-invariantly associated with lower PMS during recovery (-0.44 units 95% CI: -0.70 to -0.18). In addition, delayed surgery was time-varying associated with HHS and EQ-5D VAS. CONCLUSIONS: The associations between in-hospital waiting time and postoperative functional score suggest that delayed surgery can lead to poor functional outcomes, especially in patients waiting longer than 72 h from injury. Delayed surgery mainly impacted hip function and mobility recovery with a slower speed in early recovery of the first 3 months. More attention should be paid to mechanisms behind the associations between delayed surgery on general healthy status.

Prospective randomized multicenter noninferiority clinical trial evaluating the use of TFN-advancedTM proximal femoral nailing system (TFNA) for the treatment of proximal femur fracture in a Chinese population.

PURPOSE: To evaluate whether the 24-weeks postoperative fracture union rate for the investigational TFNA intramedullary nail was non-inferior compared to the control product PFNA-II. METHODS: The study was a prospective, randomized, single-blind, noninferiority dual-arm study drawing from 9 trauma centers across China, between November 2018 and September 2020, with follow-up measurements at 24 weeks after internal fixation. The full analysis data set (FAS [Intent-to-Treat]) was analyzed and is summarized here. The primary outcome was fracture union rate, a composite score combining clinical and radiographic assessment. Secondary endpoints comprised (a) clinical outcomes including (1) SF-12, (2) Harris Hip, and (3) EQ-5D Scores, (b) radiographic incidence of complications such as loosening or cut-out requiring revision, (c) revision rates, (d) reoperation rates, and (e) adverse events, including 24-weeks revision and reoperation rates. RESULTS: Both TFNA and PFNA-II group fracture healing rates were 100% at 24 weeks; TFNA was therefore shown to be non-inferior to PFNA-II. With baseline data matched in all parameters except age in both the TFNA and PFNA-II groups, comparisons of union rates, SF-12, Harris Hip, and EQ-5D Scores yielded p values > 0.05 indicating no significant difference between the two groups, further supporting the noninferiority of TFNA. In both groups, revision and re-operation rates were 0, and the incidences of serious adverse events were 19.4% and 17.4%, respectively. CONCLUSION: In terms of fracture union rate at 24 weeks, the DePuy Synthes Trochanteric Fixation Nail Advanced (TFNA) was not inferior to the marketed Proximal Femoral Nail Antirotation (PFNA-II) device produced by the same manufacturer. Secondary and safety outcomes showed no significant differences between the two groups. REGISTRATION: Registration was completed at ClinicalTrials.gov NCT03635320.

The role of Sirt6 in osteoarthritis and its effect on macrophage polarization.

Osteoarthritis (OA), the commonest arthritis type, features irreversible cartilage loss and synovitis. It was reported that macrophages have an important function in synovial inflammation, and our team revealed that the amounts of Sirt6, a nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylase, decrease during synovial inflammation and osteoarthritis. This work aimed to examine the anti-inflammatory properties of Sirt6 in synovial inflammation. Firstly, we compared Sirt6 amounts in acute meniscus injury and OA human knee synovial tissue samples by immunofluorescence and immunoblot. Secondly, Sirt6's suppressive effects on inflammatory markers and macrophage polarization were evaluated. Finally, OA mice were histologically evaluated, and serum inflammatory factors were detected for assessing the impact of Sirt6 overexpression on the mouse synovium. We found significantly lower interleukin-4 (IL-4) amounts and M2 polarization in OA patients compared with control individuals. The expression of Sirt6 was lower in RAW264.7 cells of the lipopolysaccharides (LPS) + interferon-gamma (IFN-γ) group compared with the phosphate buffer saline (PBS) group, but higher than in the IL-4 group. The polarization of macrophages affected Sirt6 expression, which was reduced and elevated in M1 and M2 macrophages, respectively. Sirt6 inhibition could promote the release of proinflammatory cytokines by macrophages in the synovial membrane, induce M1 polarization in macrophages and inhibit M2 polarization in vitro, and Sirt6 overexpression alleviated osteoarthritis in vivo. These data strongly suggested that Sirt6 could inhibit synovial inflammation. Thus, this study provides a novel therapeutic target in osteoarthritis.

LncRNA PART1/miR-185-5p/RUNX3 feedback loop modulates osteogenic differentiation of bone marrow mesenchymal stem cells.

BACKGROUND: Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is essential for bone formation, and its dysfunction is reported to be associated with osteoporosis (OP). Recent researches have determined that lncRNA PART1 participates in the pathogenesis of multiple diseases. However, its role in modulating osteogenic differentiation of hBMSCs is unclear. METHODS: PART1, miR-185-5p, and RUNX3 levels were assessed via RT-qPCR. The protein levels of OCN, OSN, and COL1A1 were measured by western blotting. The osteoblastic phenotype was evaluated via ALP activity and ARS staining. The relationship between miR-185-5p and PART1 or RUNX3 was validated by luciferase reporter, RIP assays. RESULTS: PART1 and RUNX3 expression were enhanced during hBMSC osteogenic differentiation. PART1 deletion decreased OCN, OSN, and COL1A1 levels and weakened ALP activity, but promoted the apoptosis of hBMSCs. Moreover, PART1 served as a ceRNA to influence the RUNX3 level via targeting miR-185-5p. In addition, RUNX3 was verified to activate the transcription of PART1 in hBMSCs. Finally, rescue assays indicated that suppression of miR-185-5p or addition of RUNX3 partially abolished the effects of PART1 knockdown on the levels of OCN, OSX, and COL1A1 levels, ALP activity, and apoptosis. CONCLUSION: Our study elaborated that PART1/miR-185-5p/RUNX3 feedback contributed to osteogenic differentiation and inhibited the hBMSCs apoptosis, suggesting that PART1 might be a novel target for OP treatment.

A novel dynamic electromagnetic tracking navigation system for distal locking of intramedullary nails.

BACKGROUND: The accurate distal locking of intramedullary (IM) nails is a clinical challenge for surgeons. Although many navigation systems have been developed, a real-time guide method with free radiation exposure, better user convenience, and high cost performance has not been proposed. METHODS: This paper aims to develop an electromagnetic navigation system named TianXuan-MDTS that provides surgeons with a proven surgical solution. And the registration method with external landmarks for IM nails and calibration algorithm for guiders were proposed. A puncture experiment, model experiments measured by 3D Slicer and cadaver experiments (2 cadaveric leg specimens and 6 drilling operations) are conducted to evaluate its performance and stability. RESULTS: The registration deviations (TRE) is 1.05± 0.13 mm. In the puncture experiment, a success rate of 96% can be achieved in 45.94 s. TianXuan-MDTS were evaluated on 3 tibia model. The results demonstrated that all 9 screw holes were successfully prepared at a rate of 100% in 91.67 s. And the entry point, end point, and angular deviations were 1.60±0.20 mm, 1.47±0.18 mm, and 3.10±0.84°, respectively. Postoperative fluoroscopy in cadaver experiments showed that all drills were in the distal locking holes, with a success rate of 100% and the average time 143.17± 18.27 s. CONCLUSIONS: The experimental results indicate that our system with novel registration and calibration methods could serve as a feasible and promising tool to assist surgeons during distal locking.

Comprehensive RNA expression profile of therapeutic adipose­derived mesenchymal stem cells co­cultured with degenerative nucleus pulposus cells.

Stem cell­based therapy is a promising alternative to conventional approaches to treating intervertebral disc degeneration (IDD). However, comprehensive understanding of stem cell­based therapy at the gene level is still lacking. In the present study, we identified the expression profiles of messenger RNAs (mRNAs) and long non­coding RNAs (lncRNAs) expressed within a co­culture system of adipose­derived mesenchymal stem cells (ASCs) and degenerative nucleus pulposus cells (NPCs) and explored the signaling pathways involved and their regulatory networks. Microarray analysis was used to compare ASCs co­cultured with degenerative NPCs to ASCs cultured alone, and the underlying regulatory pattern, including the signaling pathways and competing endogenous RNA (ceRNA) network, was analyzed with robust bioinformatics methods. The results showed that 360 lncRNAs and 1757 mRNAs were differentially expressed by ASCs, and the microarray results were confirmed by quantitative PCR. Moreover, 589 Gene Ontology terms were upregulated, whereas 661 terms were downregulated. A total of 299 signaling pathways were significantly altered. A Path­net and a Signal­net were built to show interactions among differentially expressed genes. An mRNA­lncRNA co­expression network was constructed to reveal the interplay among differentially expressed mRNAs and lncRNAs, whereas a ceRNA network was built to investigate their connections with microRNAs involved in IDD. To the best of our knowledge, this original and comprehensive exploration reveals differentially expressed lncRNAs and mRNAs of ASCs stimulated by degenerative NPCs, underscoring the regulation pattern within the co­culture system at the gene level. These data may further understanding of NPC­directed differentiation of ASCs and facilitate the application of ASCs in future treatments for IDD.

Diagnostic value of intraoperative tap test for acute deltoid ligament injury.

PURPOSE: Deltoid ligament injuries appear with isolated or even no displacement of the lateral malleolus fracture which could easily lead to misdiagnosis, which frequently brings about ankle medial instability and talus shift that eventually lead to the occurrence of ankle osteoarthritis. This study is aimed to investigate the value of the tap test for assessing the integrity of the deltoid ligament intraoperatively. METHODS: Ninety-two patients with malleolar fractures and possible acute deltoid ligament injury treated in our hospital from March 2013 to May 2016 were enrolled in this prospective study. The gravity stress test and tap test were performed preoperatively by three physicians independently before and after fixation of the fibula. The sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates of both tests were determined based on medial malleolus exploration for the integrity of the deltoid ligament. The inter-observer consistency was also analyzed. RESULTS: Forty seven (51.1%) versus fifty two (56.5%) of the 92 patients tested positive for deltoid ligament injury according to the preoperative gravity stress test or the subsequent tap test. Forty-eight cases (52.2%) were confirmed during surgery. The sensitivity of gravity stress test was lower than that of tap test (95.8% vs 100%), and specificity of gravity stress test was the same as tap test (97.7% vs 97.7%). Between gravity stress test and tap test, the positive and negative predictive values were 97.9% vs 92.3% and 95.6% vs 100%, and the false-positive and false-negative rates were 2.3% vs 9.09% and 4.2% vs 0%, respectively. Between the two tests results, the percentage of inter-observer agreement was > 90% (kappa coefficient > 0.80). CONCLUSION: The tap test has the advantages of high sensitivity, simple operation, and less radiation exposure, suggesting that it is of high diagnostic value for assessing the integrity of the acute deltoid ligament.

Anatomic Restoration of Triple Disruption of the Superior Shoulder Suspensory Complex: A Case Report and Review of the Literature.

BACKGROUND: Multiple disruptions of the superior shoulder suspensory complex (SSSC) involving more than two components are extremely rare. In some extreme situations, three components of the SSSC structure can be involved. The ideal treatment for this type of injury is debatable. CASE PRESENTATION: A 21-year-old woman was referred to our emergency center following a traffic accident. A three-dimensional CT scan showed triple disruption of the SSSC involving concomitant ipsilateral fractures of the coracoid, the acromion, and the distal clavicle. The connection between the upper limber and the axial skeleton was destroyed. There was no evidence of associated injury and the neurovascular examination of the injured upper limb was normal. The patient underwent an open reduction and internal fixation to restore the anatomic integrity of the SSSC. The arm was supported in a broad arm sling for 2 weeks after surgery. Gentle passive range of motion activity under analgesic was encouraged from the second day postoperatively. One year and half after the operation, the patient had regained pain free and unrestricted shoulder stability and mobility. CONCLUSION: The manifestations of multiple disruptions of the SSSC may be variable. This case illustrated the challenges of treating the multiple disruption of the SSSC structure. It also showed that surgical intervention for this rare combination injury yields an excellent functional result. The good outcome achieved in this patient demonstrates that surgical intervention might be an optional resolution for multiple disruptions of the SSSC.

Management of Dislocation of the Shoulder Joint with Ipsilateral Humeral Shaft Fracture: Initial Experience.

OBJECTIVE: To gain a better understanding of the traumatic mechanism and to develop appropriate treatment for dislocation of the shoulder joint with an ipsilateral humeral shaft fracture. METHODS: This was an observational and descriptive study. Nine patients with traumatic shoulder dislocations associated with ipsilateral humeral shaft fractures who visited the emergency room and received treatment from January 2012 to June 2018 were retrospectively analyzed. CT with three-dimensional reconstruction was performed to provide precise anatomical information of the fractures. The traumatic event and the type of fracture of the humeral shaft were analyzed to help determine the trauma mechanism. Closed reduction of the dislocation was attempted at once under intravenous anesthesia. One patient died the following day due to unrelated causes. All humeral shaft fractures of the eight patients received internal fixation, and then reduction of the dislocation was performed again if previous attempts failed. The affected limb was immobilized in a sling for 3 weeks postoperatively, and then active and passive movement was encouraged. Patients were evaluated based on clinical and radiographic examinations, shoulder joint range of motion, Constant-Murley score, and subjective shoulder value. RESULTS: Four cases in the present study could not give a clear description of the traumatic procedure. The other five patients suffered a second strike on their upper arms when they were hurt, with low mobility and high pain in the shoulder region. Seven cases were simple fractures and two were wedge fractures. According to the AO/OTA classification system, four cases were type 12-A2, three were type 12-A3, and two were type 12-B2. Six patients successfully obtained closed manipulative reduction of the shoulder dislocation in the acute stage. The follow-up time ranged from 18 to 31 months. No deep wound infections were encountered. All fractures healed uneventfully. The union time ranged from 4 to 6 months. At the final follow-up, shoulder range-of-motion values were found to range from 140° to 170° forward flexion, 30° to 40° extension, 40° to 45° adduction, 150° to 170° abduction, 50° to 60° internal rotation, and 50° to 60° external rotation; no recurrent instability of the shoulder joint occurred; the Constant-Murley score was 89.5 ± 3.7 points (range: 84-94 points); the subjective shoulder value was 89.4% ± 6.3% (range: 75%-95%). CONCLUSION: Shoulder dislocation most likely occurs first with an axial force or a direct posteroanterior force and a subsequent force results in the shaft fracture. For patients with mid-distal humerus fractures, closed manipulative reduction of the joint is usually effective. After success of closed reduction, surgery for the humeral shaft fracture is advocated to ensure stability and to make patient nursing convenient. In cases with fractures in the proximal third of the humeral shaft, fixation is suggested beforehand to help reduce the shoulder dislocation.

SENP3 Suppresses Osteoclastogenesis by De-conjugating SUMO2/3 from IRF8 in Bone Marrow-Derived Monocytes.

Bone metabolism depends on the balance between osteoclast-driven bone resorption and osteoblast-mediated bone formation. Diseases like osteoporosis are characterized by increased bone destruction due to partially enhanced osteoclastogenesis. Here, we report that the post-translational SUMO modification is critical for regulating osteoclastogenesis. The expression of the SUMO-specific protease SENP3 is downregulated in osteoclast precursors during osteoclast differentiation. Mice with SENP3 deficiency in bone marrow-derived monocytes (BMDMs) exhibit more severe bone loss due to over-activation of osteoclasts after ovariectomy. Deleting SENP3 in BMDMs promotes osteoclast differentiation. Mechanistically, loss of SENP3 increases interferon regulatory factor 8 (IRF8) SUMO3 modification at the K310 amino acid site, which upregulates expression of the nuclear factor of activated T cell c1 (NFATc1) and osteoclastogenesis. In summary, IRF8 de-SUMO modification mediated by SENP3 suppresses osteoclast differentiation and suggests strategies to treat bone loss diseases.

Clinical and radiological short-term outcomes of pubic symphysis diastasis treated with modified pedicle screw-rod fixation.

PURPOSE: Pubic symphysis diastasis with an incidence of approximately 20% in pelvic fractures is a severe lesion which needs to be treated properly. The objective of this retrospective study was to describe and evaluate the clinical and radiological outcomes including its advantages and limitations of this modified minimal invasive technique. METHODS: Totally 29 patients with pubic symphysis diastasis, with or without posterior ring instability, were treated by modified pedicle screw-rod fixation (modified PSRF) between January 2010 and December 2016. The duration from injury to surgery, operation time, intraoperative blood loss as well as complications were recorded. During follow-up, the functional outcomes were assessed according to the Majeed evaluation criteria 1 year postoperatively. The evaluation of the postoperative reduction quality was carried out according to Matta criteria. RESULTS: According to Tile classification, there were 9 cases of Type B1 underwent only anterior-modified PSRF and 20 cases of Type C1 experienced anterior-modified PSRF combined with posterior fixation. The duration from injury to operation, operation time and intraoperative blood loss were 3.27 days (range 1-6 days), 42.07 min (range 38-45 min), and 46.14 ml (range 40-55 ml). The results of reduction quality were rated as excellent in 16, good in 11 and fair in 2 based on Matta criteria. The Majeed functional scores ranged from 68 to 95 and there were excellent in 15, good in 12 and fair in 2. No patients experienced incision infection. Slight loosening of middle-two screws was verified during follow-up in one patient. Two patients underwent femoral nerve palsy. Irritation to the LFCN was detected in four patients. CONCLUSIONS: Modified PSRF can be performed as an alternative to manage pubic symphysis diastasis due to its merits of minimal invasive, less blood loss, less soft tissue injuries as well as shorter operation time, even with the early weight-bearing. TRIAL REGISTRATION: Researchregistry3905.

Axial Micromotion Locking Plate Construct Can Promote Faster and Stronger Bone Healing in an Ovine Osteotomy Model.

Fixing bone fractures with controlled axial interfragmentary micromotion improves bone healing; however, the optimal type of implant construct for this purpose is still lacking. The present study describes a novel axial micromotion locking plate (AMLP) construct that allows axial interfragmentary micromotion of 0.3 or 0.6 mm. We investigated whether the AMLP constructs enhance bone healing compared to an ordinary locking plate (LP) using an ovine osteotomy model. The stiffness of the constructs was tested under axial loading. We created a 3-mm osteotomy in the left hind leg tibia of sheep that was then stabilized with a 0.3- or 0.6-mm AMLP or LP construct (n = 6/group). Bone healing was monitored weekly by X-ray radiography starting from week 3 after surgery. At week 9, the specimens were collected and evaluated by computed tomography and torsional testing. We found that the AMLPs had a lower stiffness than the LP; in particular, the stiffness of the 0.6-mm AMLP construct was 86 and 41% lower than that of the LP construct for axial loads <200 and >200 N, respectively. In the in vivo experiments, tibial osteotomies treated with the 0.6-mm AMLP construct showed the earliest maximum callus formation (week 5) and the highest volume of bone callus (9.395 ± 1.561 cm3 at week 9). Specimens from this group also withstood a 27% greater torque until failure than those from the LP group (P = 0.0386), with 53% more energy required to induce failure (P = 0.0474). These results demonstrate that AMLP constructs promote faster and stronger bone healing than an overly rigid LP construct. Moreover, better bone healing was achieved with an axial micromotion of 0.6 mm as compared to 0.3 mm.

Management of Low-Energy Basicervical Proximal Femoral Fractures by Proximal Femoral Nail Anti-Rotation.

OBJECTIVE: To evaluate clinical and radiological outcomes of proximal femoral nail anti-rotation (PFNA-II) devices and demonstrate the effectiveness of PFNA-II for the treatment of basicervical fractures in elderly patients. METHODS: A retrospective review of all patients treated with PFNA-II for a proximal femoral fracture between January 2013 and February 2017 at three different institutions (Shanghai General Hospital, Shanghai Punan Hospital and Shanghai Seventh People's Hospital) was conducted. The X-ray films were strictly reviewed by three trauma surgeons and a professional radiology doctor. Patients over 60 years of age who met the following criteria were included: (i) sustained low-energy trauma; (ii) a two-part fracture; (iii) fracture line located at the base of the femoral neck and that was medial to the intertrochanteric line and exited above the lesser trochanter but was more lateral than a classic transcervical fracture. Follow-up time should be longer than 6 months. A total of 52 patients who met the inclusion criteria were selected. The average age at diagnosis was 75.1 years (range, 63-91 years); 13 patients were men and 39 were women. The same proximal femoral nail anti-rotation devices and the same surgical procedures were applied to all patients. Postoperative radiographic union time and modified Harris hip scores were used as major indicators for evaluating the effectiveness of surgery. RESULTS: The average follow-up period was 22.5 months (18.5, 23.9, and 21.2 months, respectively) and radiographic unions were observed at an average of 19.6 weeks (range, 12-28 weeks). The patients were evaluated immediately after surgery, as well as 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Of the 49 patients, 38 had good reduction qualities (75.5%), 9 acceptable (18.3%), and 3 poor (6.1%). Radiographic union was confirmed in all fractures at an average of 19.6 weeks (range, 12-28 weeks). The mean Harris hip score was 84.9 (range, 65-99): excellent in 9 patients (18.36%), good in 30 (61.22%), medium in 8 (16.32%), and poor in 2 (4.08%). Slight persistent pain occurred in 3 patients, but these patients could still walk with the help of a cane. Two patients had symptoms of excessive telescoping. Eight patients experienced postoperative medical complications, mainly pneumonia and urinary tract infection. CONCLUSION: Based on the clinical and radiological outcomes, the PFNA-II devices provide strong rotational stability and excellent clinical prognosis, and are an appropriate treatment option for basicervical proximal femoral fracture in elderly patients.

Porous Se@SiO2 nanospheres attenuate cisplatin-induced acute kidney injury via activation of Sirt1.

Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.

Porous Se@SiO2 nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model.

Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2 nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se2- to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO2 nanocomposite. The morphology of porous Se@SiO2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO2 nanocomposite. Results: In vitro, intervention with porous Se@SiO2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H2O2-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO2 nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO2 nanocomposite may provide clinic benefit for bone tissue engineering.

Nicotinamide mononucleotide alleviates Aluminum induced bone loss by inhibiting the TXNIP-NLRP3 inflammasome.

Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We orally exposed AlCl3 (10 mg/L) to Sprague-Dawley rats in drinking water for 12 weeks while NMN (20 mg/kg) were intraperitoneally injected in last 4 weeks. We found that Al could induce bone damages, bone loss and oxidative stress. In addition, we showed that Al triggered inflammatory responses, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. However, NMN treatment significantly alleviated Al-induced bone injuries by decreasing bone loss, suppressing oxidative stress as well as inhibiting Thioredoxin-interacting protein (TXNIP)-NLRP3 inflammasome pathway and pro-inflammatory cytokine production in vivo and in vitro. Meanwhile, treatment with TXNIP siRNA performed the same protective effects as NMN in Al-treated MC3T3-E1 cells. Collectively, our results suggest that NMN may reduce Al-induced bone loss partly by suppression of the TXNIP-NLRP3 inflammasome pathway.

LncRNA FOXD2-AS1 regulates chondrocyte proliferation in osteoarthritis by acting as a sponge of miR-206 to modulate CCND1 expression.

Recently, accumulating evidence demonstrated that the long non-coding RNAs (lncRNAs) play important roles in osteoarthritis (OA) progression. However, the role of lncRNA FOXD2-AS1 on OA is still unclear. In the present study, qRT-PCR showed that expression of FOXD2-AS1 and Cyclin D1 (CCND1) was upregulated in OA cartilage tissues, while miR-206 expression was significantly decreased. CCK-8 and colony formation assays showed that FOXD2-AS1 could promote chondrocytes viability. Flow cytometry analysis showed that FOXD2-AS1 inhibition arrested chondrocytes in G0/G1 phase and induced cells apoptosis. Furthermore, luciferase reporter assay and RIP assay showed that FOXD2-AS1 could function as a sponge of miR-206. Rescue assays showed that miR-206 inhibitors reversed the effects of FOXD2-AS1 suppression on chondrocytes viability. In addition, we identified that CCND1 acted as a direct target of miR-206. FOXD2-AS1 suppression could inhibit CCND1 expression in chondrocytes, while miR-206 inhibitors reversed CCND1 expression. Moreover, rescue assays indicated that CCND1 overexpression reversed the effects of FOXD2-AS1 suppression on chondrocytes viability. Taken together, these data indicated that FOXD2-AS1 could promote the growth of chondrocytes by targeting miR-206/CCND1 axis.

Aberrantly expressed messenger RNAs and long noncoding RNAs in degenerative nucleus pulposus cells co-cultured with adipose-derived mesenchymal stem cells.

BACKGROUND: Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells (NPCs), especially their biological behavior under the influence of exogenous stem cells, specifically the gene expression and regulation pattern. In the present study, we aimed to determine messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs), which are differentially expressed during the co-culturing process with adipose-derived mesenchymal stem cells (ASCs) and to explore the involved signaling pathways and the regulatory networks. METHODS: We compared degenerative NPCs co-cultured with ASCs with those cultured solely using lncRNA-mRNA microarray analysis. Based on these data, we investigated the significantly regulated signaling pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Moreover, 23 micro RNAs (miRNAs), which were demonstrated to be involved in IDD were chosen; we investigated their theoretic regulatory importance associated with our microarray data. RESULTS: We found 632 lncRNAs and 1682 mRNAs were differentially expressed out of a total of 40,716 probes. We then confirmed the microarray data by real-time PCR. Furthermore, we demonstrated 197 upregulated, and 373 downregulated Gene Ontology terms and 176 significantly enriched pathways, such as the mitogen-activated protein kinase (MAPK) pathway. Also, a signal-net was constructed to reveal the interplay among differentially expressed genes. Meanwhile, a mRNA-lncRNA co-expression network was constructed for the significantly changed mRNAs and lncRNAs. Also, the competing endogenous RNA (ceRNA) network was built. CONCLUSION: Our results present the first comprehensive identification of differentially expressed lncRNAs and mRNAs of degenerative NPCs, altered by co-culturing with ASCs, and outline the gene expression regulation pattern. These may provide valuable information for better understanding of stem cell therapy and potential candidate biomarkers for IDD treatment.