Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.

Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function. The reduced expression of HNF1α is a critical event in the development of HCC, but the underlying mechanism for its degradation remains elusive. In this study, we discovered that the expression of TRIM8 was upregulated in HCC tissues, and was positively correlated with aggressive tumor behavior of HCC and shorter survival of HCC patients. Overexpression of TRIM8 promoted the proliferation, colony formation, invasion, and migration of HCC cells, while TRIM8 knockdown or knockout exerted the opposite effects. RNA sequencing revealed that TRIM8 knockout suppresses several cancer-related pathways, including Wnt/ß-catenin and TGF-ß signaling in HepG2 cells. TRIM8 directly interacts with HNF1α, promoting its degradation by catalyzing polyubiquitination on lysine 197 in HCC cells. Moreover, the cancer-promoting effects of TRIM8 in HCC were abolished by the HNF1α-K197R mutant in vitro and in vivo. These data demonstrated that TRIM8 plays an oncogenic role in HCC progression through mediating the ubiquitination of HNF1α and promoting its protein degradation, and suggests targeting TRIM8-HNF1α may provide a promising therapeutic strategy of HCC.

Biomechanical effects of S1 sacroiliac screws versus S2 sacroiliac screws on sacroiliac screws combined with a lumbar iliac fixation in the treatment of vertical sacral fractures: a biomechanical finite element analysis.

OBJECTIVE: To examine the impact of sacroiliac screw position and length on the biomechanical properties of triangular osteosynthesis in treating unilateral vertical sacral fractures and provide a clinical reference. METHODS: Unilateral Denis type II sacral fractures were modelled using finite elements to represent Tile C pelvic ring injuries. Six sacroiliac screws were used with iliolumbar fixation patterns to fix the sacral fractures, and the sacral stability, maximum pressure, and stress distribution were compared among the internal fixation modalities. RESULTS: The best vertical stability of the internal fixation model was achieved when the S1 segment was fixed with lengthened sacroiliac screws, followed by when the S1 segment was fixed using normal sacroiliac screws. There was no significant difference in vertical stability between the S1 + S2 dual-segment fixation model and the S1-segment fixation model. The maximum pressure under a vertical force of 600 N showed a trend of L5LS1 < L5NS1 < L5LS12 < L5LS2 < L5NS2 < L5NS12. CONCLUSIONS: In unilateral vertical sacral fractures (Denis II) treated with triangular osteosynthesis using triangular jointing combined with unilateral iliolumbar + sacroiliac screw fixation, the use of a single lengthened sacroiliac screw for the S1 segment is recommended to achieve the best vertical stability of the sacrum with less maximum compression on the internal fixation components. If it is not possible to apply a lengthened sacroiliac screw, the use of a normal sacroiliac screw for the S1 segment is recommended. Adding an S2 screw does not significantly increase the vertical stability of the sacrum.

Biomechanical comparison of four triangular osteosynthesis fixations for unilateral vertical sacral fractures.

To compare the stability and biomechanical characteristics of four commonly used triangular osteosynthesis techniques to treat unilateral vertical sacral fractures and provide a clinical application reference. Finite element models of Tile C-type pelvic ring injury (unilateral Denis II sacral fracture) were produced. In four models, sacral fractures were fixed with a combination of unilateral L5, unilateral L4, and L5 iliac lumbar fixation with lengthened or normal sacroiliac screws. The biomechanical properties of the four fixation models were measured and compared under bipedal stance and lumbar rotation. The fixation stability of the model with the lengthened sacroiliac screw was excellent, and the fracture end was stable. The stability of fixation using unilateral L4 and L5 segments was close to that of unilateral L5 segment fixation. Triangular osteosynthesis transverse stabilization devices using lengthened sacroiliac screws can increase the vertical stability of the sacrum after internal fixation and increase the stability of the fracture. When triangular osteosynthesis lumbar fixation segments were selected, simultaneous fixation of L4 and L5 segments versus only L5 segments did not significantly enhance the vertical stability of the sacrum or the stability of the fracture end.

Application of Digital Orthopedic Technology in Orthopedic Trauma.

In order to solve the limitation of auxiliary treatment means in the process of orthopedic trauma surgery, and further improve the effective integration of orthopedic trauma clinical surgery and computer technology, a new orthopedic trauma auxiliary treatment means based on digital orthopedic technology was proposed with the aid of virtual digital technology. The method builds a 3D model of fracture fragments through 3D orthopedic modeling and obtains a high-quality 3D model through processing. Later clinical tests verify the feasibility of this auxiliary treatment method. The test results show that the precision of the 3D reconstruction model based on custom option fitting is higher than that based on optimal option fitting, and the precision difference is within 0.2%. This result also indicates that the 3D model obtained by 3D reconstruction has higher accuracy. The results show that three-dimensional finite element modeling technology can accurately simulate the stress of the spine of orthopedic patients and can reduce the incidence of complications through preoperative diagnosis, curative effect prediction, and trauma surgery, which has a good aid for postoperative recovery.

Hsa_circ_0045714 induced by eupatilin has a potential to promote fracture healing.

It is thought that maintaining preosteoblast viability is constructive to fracture healing. Here, we explored the effects of eupatilin on preosteoblast and addressed the mechanism associated with hsa_circ_0045714. Blood specimens were collected from 32 patients with hand fracture or calcaneus fracture. MC3T3-E1 cells were treated with eupatilin. Small interfering-RNA was transfected into MC3T3-E1 cells. The ability of MC3T3-E1 cells to survive, proliferate, migrate, and express fracture-associated proteins was examined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT), 5-bromodeoxyuridine (BrdU), 24-Transwell, Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. Hsa_circ_0045714 was detected by qRT-PCR. NF-κB and PI3K/AKT were evaluated by Western blot. Eupatilin enhanced the survival, proliferation, and migration of MC3T3-E1 cells. Cyclin D1, cyclin E, collagen II, aggrecan, and sulfated glycosaminoglycan (sGAG) were upregulated, while MMP-13 was downregulated in eupatilin-treated cells. Hsa_circ_0045714 was increased in patients with hand and calcaneus fractures with the time-lapse of surgical operation. In eupatilin-treated cells, Hsa_circ_0045714 was also elevated. However, the beneficial effects of eupatilin were weakened in hsa_circ_0045714-deficient cells. Molecularly, eupatilin-induced blockage of NF-κB and activation of PI3K/AKT were abrogated in hsa_circ_0045714-silenced cells. Our results confirmed the beneficial effects of eupatilin in preosteoblast, indicating eupatilin was a promising candidate for fracture healing.

Autogenous fibula graft and cannulated screw fixation to cephalic cut out after DHS fixation: a retrospective study.

BACKGROUND: This study aimed to explore the effect of the treatment through autologous fibula graft and hollow needle fixation to treat femoral head cutting after dynamic hip screw (DHS) fixation. METHODS: A total of 41 patients were admitted to the department of orthopedic trauma and received DHS fixation. Preoperative and postoperative harris score of hip function, limb shortening length and collodiaphysial angle between operation group (n = 11) and non-operation group (n = 13) were compared. RESULTS: There was no difference between the two groups before surgery (P > 0.05). There was a difference between the preoperative and postoperative in the operation group (P < 0.05). The excellent and good rate of the hip function score in patients 6 months after the operation was 55.6%. In the operation group, the hip function score increased after surgery (P < 0.001). Except for two groups of patients before operation, there was a difference in the limb shortening length and collodiaphysial angle between the operation group and non-operation group in other time points after surgery (P < 0.001). CONCLUSION: The application of the autogenous fibula graft and hollow nail fixation was effective in treating femoral head cutting after DHS fixation, and patients' subjective evaluation and objective indicators' outcomes of follow up were satisfactory, which was worthy of clinical application.

miR-19 promotes osteosarcoma progression by targeting SOCS6.

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-19 in human osteosarcoma (OS) development. Here, we showed that miR-19 was frequently upregulated in OS tissues and cell lines. Moreover the expression of miR-19 was associated with TNM stage, metastasis, size and poor overall survival. Mechanistically, miR-19 dramatically suppressed OS growth in vitro and in vivo. Bioinformatics analyses predicted that SOCS6 is a potential target gene of miR-19 in OS, which was confirmed by luciferase-reporter assay. We also found that SOCS6 expression was downregulated and negatively correlated with miR-19 expression in OS tissues clinically. Moreover, ectopic SOCS6 could reverse miR-19 induced OS growth. Finally, JAK2/STAT3 signaling pathway involves miR-19/SOCS6-mediated OS progression. Together, our data provide important evidence for miR-19 mediated SOCS6 in OS growth and revealed miR-19/SOCS6/JAK2/STAT3 pathway as a potential therapeutic strategy for OS patients.

Genetic polymorphisms in ERCC1 and ERCC2 genes are associated with response to chemotherapy in osteosarcoma patients among Chinese population: a meta-analysis.

BACKGROUND: There existed controversies about the association between the response to chemotherapy for osteosarcoma (OS) patients and the genetic polymorphisms in excision repair cross-complementation group (ERCC1 and ERCC2) genes. We aimed to perform a meta-analysis to comprehensively evaluate the association. METHOD: We searched multiple databases for literature retrieval including the PubMED (1966 ∼ 2017), Embase (1980 ∼ 2017), and the Web of science (1945 ∼ 2017). The overall odds ratios(OR) and their corresponding 95% confidence interval (CI) were calculated for the three polymorphisms under the dominant, recessive, and allelic models. RESULTS: From six eligible articles in our study, we found that for ERCC1 rs11615 polymorphism, a significant association was detected between the chemotherapy response and the polymorphism under all three models (dominant model: OR = 2.015, P = 0.005; recessive model: OR = 1.791, P = 0.003; allelic model: OR = 1.677, P = 0.003), and OS patients carrying C allele in rs11615 polymorphism were more likely to response to chemotherapy. In terms of ERCC2 rs1799793 polymorphism, this polymorphism was significantly associated with the response to chemotherapy for OS patients under recessive model (OR = 1.337, P = 0.036), and patients with AG + AA genotype in rs1799793 polymorphism were more appropriate to receive chemotherapy. With respect to ERCC2 rs13181 polymorphism, this polymorphism was not correlated with the response to chemotherapy for OS patients under all three models. CONCLUSIONS: Our meta-analysis suggested that among Chinese population, the rs11615 and rs1799793 polymorphisms were significantly correlated with the response to chemotherapy for patients with OS, and patients with CC or TC + CC genotypes in ERCC1 rs11615 polymorphism or AG + AA genotype in ERCC2 rs1799793 polymorphism were more suitable for chemotherapy.

miR-202 suppresses proliferation and induces apoptosis of osteosarcoma cells by downregulating Gli2.

Accumulating data have shown that microRNAs are involved in the pathogenesis of cancer. miR-202 has been confirmed to be downregulated in several types of human cancer. However, the expression and biological role of miR-202 in osteosarcoma (OS) carcinogenesis and progression remain unclear. In this study, we demonstrated that miR-202 expression is significantly decreased in human OS cell lines and specimens. Restoration of miR-202 expression could inhibit OS cell proliferation, induce cell apoptosis, and suppress tumor growth in nude mice models. We subsequently identified the transcription factor Gli2 as a direct target of miR-202. Overexpression of Gli2 blocked the inhibitory function of miR-202. Taken together, our results indicate that miR-202 acts as a novel tumor suppressor to regulate OS cell proliferation and apoptosis through downregulating Gli2 expression.

Sirt2 suppresses inflammatory responses in collagen-induced arthritis.

Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD(+)-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1ß (IL-1ß), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.