Inactivation of a non-canonical gp130 signaling arm attenuates chronic systemic inflammation and multimorbidity induced by a high-fat diet.

Interleukin-6 (IL-6) is a major pro-inflammatory cytokine for which the levels in plasma demonstrate a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes, primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions. Recently, we discovered that a non-canonical signaling pathway downstream of tyrosine (Y) 814 within the intracellular domain of gp130, the IL-6 co-receptor, is responsible for the recruitment and activation of SRC family of kinases (SFK). Mice with constitutive genetic inactivation of gp130 Y814 (F814 mice) show accelerated resolution of inflammatory response and superior regenerative outcomes in skin wound healing and posttraumatic models of osteoarthritis. The current study was designed to explore if selective genetic or pharmacological inhibition of the non-canonical gp130-Y814/SFK signaling reduces systemic chronic inflammation and multimorbidity in a high-fat diet (HFD)-induced model of accelerated aging. F814 mice showed significantly reduced inflammatory response to HFD in adipose and liver tissue, with significantly reduced levels of systemic inflammation compared to wild type mice. F814 mice were also protected from HFD-induced bone loss and cartilage degeneration. Pharmacological inhibition of gp130-Y814/SFK in mice on HFD mirrored the effects observed in F814 mice on HFD; furthermore, this pharmacological treatment also demonstrated a marked increase in physical activity levels and protective effects against inflammation-associated suppression of neurogenesis in the brain tissue compared to the control group. These findings suggest that selective inhibition of SFK signaling downstream of gp130 receptor represents a promising strategy to alleviate systemic chronic inflammation. Increased degenerative changes and tissue senescence are inevitable in obese and aged organisms, but we demonstrated that the systemic response and inflammation-associated multi-morbidity can be therapeutically mitigated.

The impact and mechanism of nerve injury on bone metabolism.

With an increasing understanding of the mechanisms of fracture healing, it has been found that nerve injury plays a crucial role in the process, but the specific mechanism is yet to be completely revealed. To address this issue and provide novel insights for fracture treatment, we compiled this review. This review aims to study the impact of nerve injury on fracture healing, exploring the role of neurotrophic factors in the healing process. We first revisited the effects of the central nervous system (CNS) and the peripheral nervous system (PNS) on the skeletal system, and further explained the phenomenon of significantly accelerated fracture healing under nerve injury conditions. Then, from the perspective of neurotrophic factors, we delved into the physiological functions and mechanisms of neurotrophic factors, such as nerve growth factor (NGF), Neuropeptides (NPs), and Brain-derived neurotrophic factor (BDNF), in bone metabolism. These effects include direct actions on bone cells, improvement of local blood supply, regulation of bone growth factors, control of cellular signaling pathways, promotion of callus formation and bone regeneration, and synergistic or antagonistic effects with other endocrine factors, such as Sema3A and Transforming Growth Factor ß (TGF-ß). Finally, we discussed the treatments of fractures with nerve injuries and the future research directions in this review, suggesting that the relationship between nerve injury and fracture healing, as well as the role of nerve injury in other skeletal diseases.

Mitigating nonlinear penalty induced from a low-speed optical supervisory channel on coherent signals.

With the increasing signal rates of a long-haul backbone dense-wavelength-division-multiplexing (DWDM) transmission system, e.g., from 100 Gb/s to 400 Gb/s and even to 800 Gb/s, optical path impairments simultaneously become more severe. Harmful factors being formerly insignificant become noticeable, e.g., nonlinear phase noise (NPN) on main DWDM channels induced by the cross-phase modulation (XPM) from the low-speed optical supervisory channel (OSC). Field trials show that a greater than 5.13-dB penalty can be observed on the shortest channel of 400G DP-16QAM-PCS over G.654.E links, which greatly degrades the overall transmission performance and limits the maximum reach. In this paper, we propose a dual-OSC structure with opposite signals to compensate for performance degradation caused by OSC-induced NPN. This method involves no extra digital signal processing (DSP), which is not only simple but also applicable for universal signal rates. By experimental demonstration, a 1.32-dB gain in Q (dB) for 200G DP-16QAM transmission over 1618-km G.652.D can be done, almost achieving the same performance as the no OSC case.

LncRNA-COX2 inhibits Fibroblast Activation and Epidural Fibrosis by Targeting EGR1.

Rationale: Epidural fibrosis is one of the contributors to failed back surgery syndrome (FBSS) with a high incidence of about 80,000 cases per year. The fibrosis spreads from the operative region to the dura mater or the nerve root and results in functional incapacity and pain after laminectomy. Our previous study showed that down-regulation of lncRNA-COX2 is involved in the epidural scar formation. However, it remains unknown whether lncRNA-COX2 participate in the fibroblast activation and epidural fibrogenesis. Methods: LncRNA-COX2 and EGR1 expression were assessed by qRT-PCR and western blotting. Fibroblasts differentiation, proliferation and migration was determined by Collagen I/ɑ-SMA, 5-ethynyl-2'-deoxyuridine (EdU) and Transwell Assay respectively. Luciferase reporter assay was performed for the verification of target of LncRNA-COX2. Laminectomy was performed to establish the model of epidural fibrosis in mice. Epidural scar was evaluated by hematoxylin and eosin (HE) staining and Masson Trichrome staining. Results: Based on the result of transcriptome profiling, we found LncRNA-COX2 was significantly decreased in epidural tissues after laminectomy and in activated fibrotic fibroblasts. In vitro, overexpression of LncRNA-COX2 suppressed epidural fibrogenesis by inhibiting fibroblasts differentiation, proliferation and migration. Mechanistically, LncRNA-COX2 functioned as competing endogenous RNA (ceRNA) of EGR1. Gain of LncRNA-COX2 significantly decreased the expression of EGR1 and showed anti-fibrotic effect while EGR1 was markedly increased after loss of LncRNA-COX2. In vivo, LncRNA-COX2 attenuated laminectomy-induced epidural fibrosis in mice. Conclusion: In summary, the results demonstrated that LncRNA-COX2 showed anti-fibrotic effect by targeting EGR1 and identified LncRNA-COX2 as therapeutic molecule for preventing aberrant epidural fibrosis.

Long-haul intermodal-MIMO-free MDM transmission based on a weakly coupled multiple-ring-core few-mode fiber.

Mode-division multiplexing (MDM) technique based on few-mode fibers (FMFs) can achieve multiplicative growth in single-fiber capacity by using different linearly polarized (LP) modes or mode groups as spatial channels. However, its deployment is seriously impeded because multiple-input multiple-output digital signal processing (MIMO-DSP) with huge computational load must be adopted to combat intermodal crosstalk for long-haul FMF transmission. In this paper, we present an intermodal-MIMO-free MDM transmission scheme based on weakly coupled multiple-ring-core FMF, which achieves ultralow distributed modal crosstalk (DMC) so that the signal in each LP mode can be independently received by single-LP-mode MIMO-DSP even after hundreds-of-kilometer transmission. Evaluation method for the required DMC levels is proposed and different transmission reaches are investigated by simulation. By adopting an improved method for quantitative DMC measurement, we show that the required DMC level for long-haul transmission is feasible. Finally, we experimentally demonstrate 1800-km LP01/LP02 multiplexed transmission and 525-km LP01/LP21/LP02 multiplexed transmission only adopting 2×2 or 4×4 MIMO-DSP. The proposed scheme may pave the way to practical applications of long-haul MDM techniques for the first time.

Comparison of double-strand braided polyester sutures tension band (Nice knot) with cable tension band in transverse patellar fractures.

BACKGROUND: The tension band technique is the most common method for internal fixation of transverse patellar fractures. Titanium cable and high-strength sutures have been successfully applied in this treatment; however, few studies have compared the Nice knot technique using sutures with the standard cable technique. Whether the suture technique (Nice knot) provides preferable results compared with those of the cable technique is unclear. METHODS: Forty patients with transverse patellar fractures participated in this study. Twenty patients underwent sutures tension band fixation (Nice knot), and the others were managed with cable tension bands. All patients were followed up at 1, 3, 6, and 12 months. Pain was measured by VAS scores, flexion and extension of the knee were measured in degrees by goniometry, and knee function was evaluated using the Böstman clinical grading scale. RESULTS: The two groups had equal distributions in age, gender, injured side, and fracture classification. The mean operation time in the suture group was shorter (55.75±9.77 minutes versus 64.25±9.63 minutes). The VAS score was comparable in the two groups at the 1-month, 3-month, and 6-month follow-ups; however, the score was lower at 12 months postoperatively in the suture group (P=0.037). No significant difference was found in flexion, extension, Böstman score, or fracture healing time in either group (P>0.05). Postoperative complications were higher in the cable group (9 versus 2) (P = 0.031) but were mostly related to symptomatic soft tissue irritation. CONCLUSION: The suture tension band technique using braided polyester nonabsorbable sutures tied with Nice knot was as effective as the cable tension band technique for transverse patellar fracture management. However, more convenient operations, less cost and fewer complications were found in suture fixation (Nice knot).

Silencing COX-2 blocks PDK1/TRAF4-induced AKT activation to inhibit fibrogenesis during skeletal muscle atrophy.

Skeletal muscle atrophy with high prevalence can induce weakness and fatigability and place huge burden on both health and quality of life. During skeletal muscle degeneration, excessive fibroblasts and extracellular matrix (ECM) accumulated to replace and impair the resident muscle fiber and led to loss of muscle mass. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in synthesis of prostaglandin, has been identified as a positive regulator in pathophysiological process like inflammation and oxidative stress. In our study, we found injured muscles of human subjects and mouse model overexpressed COX-2 compared to the non-damaged region and COX-2 was also upregulated in fibroblasts following TGF-ß stimulation. Then we detected the effect of selective COX-2 inhibitor celecoxib on fibrogenesis. Celecoxib mediated anti-fibrotic effect by inhibiting fibroblast differentiation, proliferation and migration as well as inactivating TGF-ß-dependent signaling pathway, non-canonical TGF-ß pathways and suppressing generation of reactive oxygen species (ROS) and oxidative stress. In vivo pharmacological inhibition of COX-2 by celecoxib decreased tissue fibrosis and increased skeletal muscle fiber preservation reflected by less ECM formation and myofibroblast accumulation with decreased p-ERK1/2, p-Smad2/3, TGF-ßR1, VEGF, NOX2 and NOX4 expression. Expression profiling further found that celecoxib could suppress PDK1 expression. The interaction between COX-2 and PDK1/AKT signaling remained unclear, here we found that COX-2 could bind to PDK1/AKT to form compound. Knockdown of COX-2 in fibroblasts by pharmacological inactivation or by siRNA restrained PDK1 expression and AKT phosphorylation induced by TGF-ß treatment. Besides, si-COX-2 prevented TGF-ß-induced K63-ubiquitination of AKT by blocking the interaction between AKT and E3 ubiquitin ligase TRAF4. In summary, we found blocking COX-2 inhibited fibrogenesis after muscle atrophy induced by injury and suppressed AKT signaling pathway by inhibiting upstream PDK1 expression and preventing the recruitment of TRAF4 to AKT, indicating that COX-2/PDK1/AKT signaling pathway promised to be target for treating muscle atrophy in the future.

LINC00266-1/miR-548c-3p/SMAD2 feedback loop stimulates the development of osteosarcoma.

Osteosarcoma (OS) is one of the most common primary bone malignancies and accounts for 3.4% of pediatric tumors. Its 5-year survival is as low as about 20%. Differentially expressed lncRNAs in OS profiling were searched in the downloaded profile of GSE12865. As a result, LINC00266-1 was detected to be upregulated in both GSE12865 and OS tissues we collected. SMAD2 was the downstream target binding to promoter sites of LINC00266-1, displaying a positive regulatory interaction. Knockdown of LINC00266-1 suppressed the proliferative and metastatic abilities, and promoted the apoptosis in OS cells. Besides, knockdown of LINC00266-1 significantly alleviated the growth of OS in vivo. MiR-548c-3p was the sponge miRNA of LINC00266-1, which was able to reverse the regulatory effects of LINC00266-1 on OS cell phenotypes. Moreover, miR-548c-3p bound to the 3'-UTR of SMAD2 and thus downregulated SMAD2. Overexpression of SMAD2 partially reversed the regulatory effects of LINC00266-1 on OS cell phenotypes. Finally, we have identified that LINC00266-1/miR-548c-3p/SMAD2 feedback loop was responsible for stimulating the development of OS.

Long-distance transmission of quantum key distribution coexisting with classical optical communication over a weakly-coupled few-mode fiber.

Quantum key distribution (QKD) is one of the most practical applications in quantum information processing, which can generate information-theoretical secure keys between remote parties. With the help of the wavelength-division multiplexing technique, QKD has been integrated with the classical optical communication networks. The wavelength-division multiplexing can be further improved by the mode-wavelength dual multiplexing technique with few-mode fiber (FMF), which has additional modal isolation and large effective core area of mode, and particularly is practical in fabrication and splicing technology compared with the multi-core fiber. Here, we present for the first time a QKD implementation coexisting with classical optical communication over weakly-coupled FMF using all-fiber mode-selective couplers. The co-propagation of QKD with one 100 Gbps classical data channel at -2.60 dBm launched power is achieved over 86 km FMF with 1.3 kbps real-time secure key generation. Compared with single-mode fiber using wavelength-division multiplexing, given the same fiber-input power, the Raman noise in FMF using the mode-wavelength dual multiplexing is reduced by 86% in average. Our work implements an important approach to the integration between QKD and classical optical communication and previews the compatibility of quantum communications with the next-generation mode division multiplexing networks.

Treatment of a high-energy transsyndesmotic ankle fracture: A case report of "logsplitter injury".

INTRODUCTION: The "logsplitter injury" is a special type of ankle fractures that results from high energy violence with combined rotational forces and axial loads. So far, the diagnose and treatment of "logsplitter injury" remain largely unsettled and related literature is rare. PATIENT CONCERNS: An 18-year-old male fell from a fence and got his left ankle injured with severe malformation and swollen condition. No open wound was observed. DIAGNOSIS: Logsplitter injury, ankle fracture (AO/OTA classification 44C1.1, Lauge-Hansen classification: pronation-external rotation). INTERVENTIONS AND OUTCOMES: The patient was initially treated by internal fixation of fibular, repair of deltoid ligaments, and 1 syndesmotic screw fixation. When the X-ray applied after surgery, another 2 syndesmotic screws were performed to enhance stability. The syndesmotic screws were removed at 12-week and 16-week respectively. The patient was allowed for full weight-bearing immediately. However, the syndesmotic space was slightly increased compared to the contralateral side in CT views at 1-year follow-up, the function outcome was satisfied. CONCLUSION: The logsplitter injury is a high-energy ankle fracture that requires both axial and rotational load. It is categorized as 44B or 44C by the AO/OTA classification. In the classification scheme of Lauge-Hansen, our case is in line with the pronation-external rotation classification. Anatomic reduction and fixation of ankle syndesmotic injuries are required to restore the biomechanics of the ankle joint so that long-term complications can be prevented. How to fixation the syndesmosis, whether to reconstruct the deltoid ligament remains in debate in the treatment of logsplitter injury, whether and when to remove the syndesmotic screws were still debated. Correct surgical intervention is successful in the treatment of "logsplitter injury", however, the optimal fixation of syndesmosis and repair of deltoid ligaments need further investigate.

Excess administration of miR-340-5p ameliorates spinal cord injury-induced neuroinflammation and apoptosis by modulating the P38-MAPK signaling pathway.

Spinal cord injury (SCI) is a destructive polyneuropathy that can result in loss of sensorimotor function and sphincter dysfunction, and even death in critical situations. MicroRNAs (miRs) are a series of non-coding RNA molecules that are involved in transcriptional regulation. Previous studies have demonstrated that modulation of multiple miRs is involved in neurological recovery after SCI. However, the functions of miR-340-5p in SCI remain uncertain. Therefore, we probed the therapeutic effect and mechanism of miR-340-5p in microglia in vitro and in vivo in SCI rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were employed to examine the alterations in miR-340-5p and P38 levels in SCI rats. miR-340-5p targets in microglia were ascertained using luciferase reporter assays, immunofluorescence analyses, and western blotting. We also established an SCI model and administered miR-340-5p. The effects of miR-340-5p on the amelioration of inflammation, oxidative stress, and apoptosis following SCI were assessed using immunofluorescence, immunohistochemistry, and histological analyses. Finally, locomotor function recovery was determined using the Basso, Beattie, Bresnahan rating scale. In our study, the expression profiles and luciferase assay results clarified that P38 was a target of miR-340-5p, which was associated with activation of the P38-MAPK signaling pathway. Elevation of miR-340-5p decreased P38 expression, subsequently inhibiting the inflammatory reaction. SCI-induced secondary neuroinflammation was relieved under miR-340-5p treatment. Moreover, by controlling neuroinflammation, the increased levels of miR-340-5p might counter oxidative stress and reduce the degree of apoptosis. We also observed decreasing gliosis and glial scar formation and increasing neurotrophin expression at the chronic stage of SCI. Together, these potential effects of miR-340-5p treatment ultimately improved locomotor function recovery in SCI rats.

Prototype system for real-time IM/DD MDM transmission based on multiple-ring-core FMF and degenerate-mode-selective reception.

Multiple-input-multiple-output digital signal processing (DSP) has become a severe bottleneck for mode division multiplexing (MDM) because of its huge computational complexity. In this paper, we propose a novel scheme for real-time DSP-free intensity-modulation/direct-detection (IM/DD) MDM transmission, in which the transmission few-mode fiber (FMF) is characterized by multiple-ring-core structure to suppress modal crosstalk among each LP mode, while each pair of non-circularly-symmetric degenerate modes is simultaneously demultiplexed by a degenerate-mode-selective fiber coupler for DSP-free reception. Based on a 10 km ultralow-modal-crosstalk double-ring-core FMF and a pair of all-fiber 4-LP-mode MUX/DEMUX, we demonstrate the first IM/DD MDM prototype system using commercial single-mode (SM) 10 Gbps SFP + modules and 4K video transceivers without any hardware modifications. The temperature and wavelength dependence are evaluated. The stable Q2-factor performance proves that it can be a smooth evolution scheme from conventional SM IM/DD systems. Moreover, the scheme can be further extended to support more modes with improved FMF design adopting more ring areas.

CircRNA LRP6 promotes the development of osteosarcoma via negatively regulating KLF2 and APC levels.

We aimed to investigate the biological functions of circLRP6 in the progression of osteosarcoma. CircLRP6 level in OS was detected by quantitative real-time polymerase chain reaction. Correlation between circLRP6 level with survival of OS patients was evaluated. Cell counting kit-8 and Transwell assay were conducted to detect proliferative, migratory and invasive capacities of OS cells. Cell cycle and apoptosis in OS cells influenced by circLRP6 were evaluated by flow cytometry. RNA immunoprecipitation was conducted to verify the binding relationship between circLRP6 with LSD1 and EZH2. Finally, the interaction between LSD1, EZH2 and promoter regions of KLF2, APC was clarified by chromatin immunoprecipitation. CircLRP6 level markedly increased in OS tissues. Besides, OS patients with high expression of circLRP6 showed shorter disease-free survival and over-all survival than those with low expression. CircLRP6 knockdown suppressed proliferative, migratory and invasive rates of OS cells. Moreover, circLRP6 knockdown induced apoptosis and arrested cell cycle in G0/G1 phase. The interaction between circLRP6 with LSD1 and EZH2 mediates their binding to the promoter regions of KLF2 and APC. Knockdown of circLRP6 weakened the binding abilities of LSD1, EZH2 to KLF2, APC. APC overexpression inhibited proliferation, induced apoptosis and arrested cell cycle. Moreover, the tumor-suppressor effect of downregulated circLRP6 on OS could be reversed by APC knockdown. Collectively, circLRP6 was highly expressed in OS and served as an oncogene by binding to LSD1 and EZH2 to inhibit expressions of KLF2 and APC.

Weakly-coupled 7-core-2-LP-mode transmission using commercial SFP + transceivers enabled by all-fiber spatial multiplexer and demultiplexer.

Spatial division multiplexing transmission over few-mode multicore fiber (FM-MCF) recently attracts great interests by simultaneously exploiting two more dimensions than conventional single mode fibers. In this paper, we propose an all-fiber spatial multiplexer (MUX) by cascading mode-selective fiber couplers (MSCs) with a fiber-bundle-type fan-in device, and spatial demultiplexer (DEMUX) by cascading a fiber-bundle-type fan-out device with degenerate-mode-selective fiber couplers and MSCs. Thanks to the low crosstalk of the FM-MCF, spatial MUX/DEMUX and their coupling, weakly-coupled 7-core-2-LP-mode real-time transmission over 1-km of FM-MCF is successfully demonstrated using 10-Gbps commercial enhanced small form-factor pluggable (SFP + ) transceivers.

Hollow-core conjoined-tube fiber for penalty-free data transmission under offset launch conditions.

Three types of hollow-core fibers, i.e., photonic-bandgap fiber, negative-curvature fiber, and conjoined-tube fiber, are compared in terms of data transmission performance. Their group velocity dispersions and group indices are measured in detail by using low-coherence interferometry. Whilst all three fibers show good performance with an optimized central launch, they behave differently under offset launch for 10 Gbit/s on-off keying transmission. We use a Q2-factor analysis method to gain insight into the data transmission over a hollow-core fiber. The low-loss, low-intermodal crosstalk conjoined-tube fiber shows great resilience to bending and offset launch compared to the other two hollow-core fibers, enabling genuine penalty-free data transmission in realistic environments.

Hsa-miR-889-3p promotes the proliferation of osteosarcoma through inhibiting myeloid cell nuclear differentiation antigen expression.

Osteosarcoma accounts for about 0.2% in human malignant solid tumors. The mortality and metastatic rates of osteosarcoma remain relatively high. MicroRNA (miRNA) is a kind of non-coding small-molecular RNA discovered in recent years. Various studies have identified the involvement of miRNA in the occurrence and development of tumor as an oncogene or tumor-suppressor gene. This study aims to investigate the effect of hsa-miR-889-3p on the progression of osteosarcoma and its underlying mechanism. Through the bioinformatics methods, we first found that hsa-miR-889-3p was upregulated in osteosarcoma, and it was a prognostic risk factor for osteosarcoma. Additionally, the gene set enrichment analysis (GSEA) revealed that hsa-miR-889-3p mainly affected cell cycle progression and proliferation of osteosarcoma. To verify the bioinformatics results, regulatory effects of hsa-miR-889-3p on osteosarcoma both in vitro and in vivo experiments were investigated. It is found that hsa-miR-889-3p could promote the proliferation of osteosarcoma cells though regulating cell cycle progression. Tumor size and growth rate of osteosarcoma were influenced by hsa-miR-889-3p in xenograft models. To further explore its potential mechanism, the target gene of hsa-miR-889-3p was predicted. Furthermore, hsa-miR-889-3p was confirmed to inhibit the expression of myeloid cell nuclear differentiation antigen (MNDA) in a targeted manner. In conclusion, hsa-miR-889-3p could promote the proliferation of osteosarcoma through inhibiting MNDA expression, which provides a potential therapeutic strategy in treatment for osteosarcoma.

LncRNA SNHG3/miRNA-151a-3p/RAB22A axis regulates invasion and migration of osteosarcoma.

To elucidate the potential function of lncRNA SNHG3 in the development of osteosarcoma. Quantitative real-time polymerase chain reaction was conducted for detection of SNHG3, miRNA-151a-3p and RAB22 A in osteosarcoma tissues and cells. Receiver operating characteristic curve was introduced to analyze the diagnostic potential of SNHG3 in osteosarcoma. Correlation between SNHG3 expression and the overall survival of osteosarcoma patients was evaluated using Kaplan-Meier method. Invasive and migratory potentials of osteosarcoma cells were examined by Transwell assay. Furthermore, dual-luciferase reporter gene assay, RNA-pull down and RIP assay were used to verify the binding of SNHG3/RAB22 A to miRNA-151a-3p. The function of SNHG3/miRNA-151a-3p/RAB22 A axis in osteosarcoma was finally confirmed by rescue experiments. SNHG3 and RAB22 A were highly expressed in osteosarcoma patients, while miRNA-151a-3p was lowly expressed. The overall survival of osteosarcoma patients with high expression of SNHG3 was shorter than those with low expression. SNHG3 overexpression markedly promoted invasive and migratory potentials of osteosarcoma cells. Through dual-luciferase reporter gene assay, both SNHG3 and RAB22 A could bind to miRNA-151a-3p. RAB22 A expression was positively regulated by SNHG3, but negatively regulated by miRNA-151a-3p. Finally, rescue experiments confirmed that RAB22 A overexpression could reverse the promotive effects of miRNA-151a-3p knockdown on invasive and migratory potentials of osteosarcoma cells. SNHG3 is highly expressed in osteosarcoma, and promotes the invasive and migratory potentials of osteosarcoma cells by absorbing miRNA-151a-3p to upregulate RAB22 A expression.

Long non-coding RNA XIST promotes osteoporosis through inhibiting bone marrow mesenchymal stem cell differentiation.

The purpose of the present study was to identify the key long non-coding (lnc)RNAs in the occurrence and development of osteoporosis (OP) and to explore the associated molecular mechanism. First, the Gene Expression Omnibus (GEO) datasets, with key words 'osteoporosis' and 'HG-133A', were screened. RankProd R package was used to calculate the dysregulated lncRNAs in OP. Following this, bone marrow mesenchymal stem cells (BM-MSCs) harvested from 3-week-old Sprague Dawley rats were employed for detection of osteoblast differentiation. Following overexpression or interference with X-inactive specific transcript (XIST), osteogenesis-associated genes and proteins in BM-MSCs were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Alkaline phosphatase (ALP) and Alizarin Red S staining were also performed to measure the osteogenic ability of BM-MSCs. Results from the two datasets indicated that 6 lncRNAs were dysregulated in OP. Notably, XIST is key lncRNA in diverse diseases, and was subsequently selected for analysis. It was revealed that XIST was significantly upregulated in plasma and monocytes from patients with OP compared with the normal controls. Furthermore, results indicated that overexpression of XIST significantly inhibited osteoblast differentiation in BM-MSCs, as evidenced by the decreased expression of ALP, bone γ-carboxyglutamic acid-containing protein and runt related transcription factor 2, reduced ALP activity and a decreased number of calcium deposits. However, interference of XIST exhibited the opposite biological effects in BM-MSCs. Taken together, XIST was highly expressed in the serum and monocytes of patients with OP. In addition, the findings suggested that XIST could inhibit osteogenic differentiation of BM-MSCs.

miRNA-544a Regulates the Inflammation of Spinal Cord Injury by Inhibiting the Expression of NEUROD4.

BACKGROUND/AIMS: To explore the potential role of miR-544a in spinal cord injury and the possible mechanism involved. METHODS: We established a mouse model with spinal cord injury to examine the changes in grip force recovery of the forelimb or the posterior limb of the mouse. Microarray was performed to achieve differentiated miRNAs in the mice. The expressions of miR-544a, MCP-1, IL36B and IL17B after spinal cord injury were detected by qRT-PCR. Subsequently, miR-544a was overexpressed to observe changes in inflammation and grip strength after spinal cord injury. Target gene of miR-544a was then predicted using bioinformatics technology. Finally, dual luciferase reporter gene assay was used to verify the binding of miR-544a to its target gene. RESULTS: Using mice models with spinal cord injury, we found that the strength of their four limbs began to recover 7 days after injury. The results of microarray and qRT-PCR confirmed that mir-544a level in mice with spinal cord injury decreased with increase of injury time, while the levels of inflammatory genes MCP-1 (monocyte chemoattractant protein-1), IL1 (interleukin-1) and TNF-α (tumor necrosis factor alpha) IL36B (interleukin-36 beta) and IL17B (interleukin-17 beta) were significantly increased. However, overexpression of miR-544a in the mice significantly reduced the level of inflammation and restored their grip strength in their four limbs. Finally, we found that miR-544a can bind to the NEUROD4 (Neurogenic differentiation 4) 3'UTR (Untranslated Region) region through bioinformatics website prediction, which was further confirmed by dual luciferase reporter assay. NEUROD4 level was significantly reduced following the overexpression of miR-544a. CONCLUSION: The expression of miR-544a was significantly decreased after spinal cord injury. High expression of miR-544a could alleviate the inflammation caused by spinal cord injury and promote the recovery of spinal cord via the inhibition of NEUROD4.

FOXP4-AS1 participates in the development and progression of osteosarcoma by downregulating LATS1 via binding to LSD1 and EZH2.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNA has been confirmed to participate in a variety of cancers. The purpose of this study was to explore the effect of FOXP4-AS1 on the development of osteosarcoma (OS) and its underlying mechanism. FOXP4-AS1 expressions in 60 OS tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). We confirmed that FOXP4-AS1 was overexpressed in OS tissues than that of paracancerous tissues. The disease-free survival and overall survival of OS patients were not correlated with age, gender and tumor location, but remarkably correlated with FOXP4-AS1 expression, tumor size and lung metastasis. For in vitro experiments, MG63 cells expressed a higher expression of FOXP4-AS1, whereas U2OS cells expressed a lower expression, which were selected for the following studies. Overexpressed FOXP4-AS1 led to enhanced proliferation, migration and invasion, shortened G0/G1 phase, as well as inhibited cell cycle. Knockdown of FOXP4-AS1 in MG63 cells obtained the opposite results. Furthermore, RIP assay indicated that FOXP4-AS1 could inhibit LATS1 expression by binding to LSD1 and EZH2, so as to participate in OS development. In conclusion, these results revealed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. Furthermore, FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1 via binding to LSD1 and EZH2.