TRIM4 Expression Related to Malignant Progression and Cisplatin Resistance in Osteosarcoma.

Osteosarcoma (OS) is a high-grade intraosseous malignancy. Twenty to thirty percent of OS patients react poorly to standard therapy with a combination of surgical resection and chemotherapy. It is necessary to find molecules that play an important role in this. This study explored the role of TRIM4 in OS chemotherapy sensitivity and malignant progression. The expression of TRIM4 in OS tissues and cells was examined by RT-qPCR, immunohistochemical staining, and western blot. Specific siRNA was transfected into U2-OS and SAOS2 cells to target TRIM4. Cell biological behavior was examined by CCK-8, Transwell, and flow cytometry experiments. Cisplatin-resistant SAOS2 (SAOS2-Cis-R) cells were established, and the effect of TRIM4 expression on the cisplatin response of SAOS2 cells was tested. Knockdown of TRIM4 significantly inhibited the proliferation, migration, and invasion of U2-OS and SAOS2 cells and induced apoptosis. TRIM4 expression was significantly higher in chemotherapy-resistant OS tissues compared to chemotherapy-sensitive OS tissues. Furthermore, the expression of TRIM4 in SAOS2-Cis-R cells was significantly increased compared to parental SAOS2 cells. Moreover, overexpression of TRIM4 enhanced cisplatin resistance in parental SAOS2 cells, while the downregulation of TRIM4 expression enhanced cisplatin sensitivity of SAOS2-Cis-R cells. High TRIM4 expression might be associated with malignant progression and poor response to chemotherapy response of OS. Targeting TRIM4 may be beneficial for OS treatment or combination therapy.

0D hybrid indium halide as a highly efficient X-ray scintillation and ultra-sensitive fluorescent probe.

Halide perovskite nanocrystal (PNC) of 3D CsPbX3 as a scintillator has aroused intensive attention with advanced applications in radiation detection and X-ray imaging. However, the low light yield and serious toxicity of Pb2+ severely hinder advanced optoelectronic applications. To reduce these fatal shortcomings, a family of new environmentally friendly 0D hybrid lead-free indium halides of [DADPA]InX6·H2O (DADPA = 3,3'-diaminodipropylamine; X = Cl and Br) was prepared. Upon UV excitation, these halides display strong broadband yellow-orange light emissions, and the photoluminescence quantum yield (PLQY) can be optimized up to near unity through the Sb3+-doping strategy. Significantly, high PLQY, negligible self-absorption and low attenuation ability toward X-ray render extraordinary scintillation performance with a high light yield of 51 875 photons MeV-1 and ultralow detection limit of 98.3 nGyair s-1, which is far superior to typical 3D PNC scintillators. Additionally, the ultra-high spatial resolution of 25.15 lp mm-1, negligible afterglow time (2.75 ms) and robust radiant stability demonstrates excellent X-ray imaging performance. To the best of our knowledge, this is the first report on X-ray scintillation based on 0D indium halide materials.

Multidisciplinary Team Led by Joint Surgeons to Rapidly Identify Spondyloarthritis.

Context: Spondyloarthritis (SpA) is a group of chronic, inflammatory, rheumatic diseases of which axial SpA and peripheral SpA are the two main types. Patients that predominantly have manifestations of axSpA may have additional peripheral-arthritis symptoms, and vice versa. For these hard-to-diagnose SpA patients, symptoms can be nonspecific and difficult to identify, making it easy to miss a diagnosis or misdiagnosis patients, resulting in disability. Objective: The study intended to evaluate the value of a multidisciplinary team (MDT) led by the joint surgeons to rapidly identify spondyloarthritis (SpA). Design: The research team designed a controlled study that analyzed the clinical data of patients with spondyloarthritis. Setting: The study was conducted in the Department of Joint Surgery at Shandong Second Provincial General Hospital in Jinan, China. Participants: Participants were 113 SpA patients at the hospital between January 2019 and January 2020. Intervention: he research team divided participants into an intervention group, the MDT group that used that model to diagnose 83 participants and the control group with 30 participants, for whom diagnoses occurred using the conventional diagnostic model. Outcome Measures: The research team collected data on participants' number of visits and number of departments visited as well as determined the amount of time that elapsed before a diagnosis occurred. The team also measured C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI) at baseline and after 3 months and 6 months treatment. Results: In the MDT group, diagnoses included: (1) axial SpA (axSpA)-73 participants, and (2) peripheral SpA-10 participants, including three with reactive arthritis, two with uveitis, and five with psoriatic arthritis. Eight participants in that group were HLA-B27 positive, and 14 had complications from a latent tuberculosis infection. In the control group, diagnoses included: (1) axSpA-25 participants; and (2) peripheral SpA-5 participants, including three with psoriatic arthritis and two with reactive arthritis. Six participants in that group were HLA-B27 positive and four had complications from a latent tuberculosis infection. The number of visits, number of departments visited, and time to diagnosis in the MDT group were significantly lower than those in the control group (P < .001). After three and six months of treatment, the MDT group's CRP, ESR, BASDAI, and BASFI were significantly lower than those at baseline (P < .001). Conclusions: The MDT model of spondyloarthritis led by joint surgeons was accurate and efficient, allowing the medical personnel to quickly identify and intervene in SpA and provide effective treatment for patients. It's a diagnosis and treatment model worthy of promotion.

Acetaminophen changes the RNA m6A levels and m6A-related proteins expression in IL-1ß-treated chondrocyte cells.

BACKGROUND: Acetaminophen is commonly recommended for the early analgesia of osteoarthritis. However, the molecular mechanism by which it acts remains unknown. The aim of this study is to investigate the effect of acetaminophen on inflammation and extracellular matrix degradation in human chondrocytes, and the possible molecular mechanisms involved in its effect. METHODS: The normal chondrocyte cell line C28/I2 was treated with interleukin-1ß to mimic the inflammatory state. Acetaminophen and the methylation inhibitor (cycloleucine) were used to treat interleukin-1ß-induced C28/I2 cells. The expression of RNA N6-methyladenosine -related proteins was detected by RT-qPCR and western blot. The total RNA N6-methyladenosine level was measured by dot blot analysis and enzyme linked immunosorbent assay. The levels of interleukin-6, interleukin-8 and anti-tumor necrosis factor-α were measured by enzyme linked immunosorbent assay. The extracellular matrix synthesis and degradation were examined by western blot. RESULTS: After interleukin-1ß stimulated C28/I2 cells, the intracellular RNA N6-methyladenosine level increased, and the expression of regulatory proteins also changed, mainly including the increased expression of methyltransferase like 3 and the downregulated expression of AlkB family member 5. The use of cycloleucine inhibited interleukin-1ß-induced inflammation and extracellular matrix degradation by inhibiting RNA N6-methyladenosine modification. In contrast, acetaminophen treatment counteracted interleukin-1ß-induced changes in RNA N6-methyladenosine levels and regulatory protein expression. Furthermore, acetaminophen treatment of interleukin-1ß-induced C28/I2 cells inhibited the secretion of interleukin-6, interleukin-8 and anti-tumor necrosis factor-α, down-regulated the expression of matrix metalloproteinase-13 and Collagen X, and up-regulated the expression of collagen II and aggrecan. In addition, AlkB family member 5 overexpression activated interleukin-1ß-induced chondrocyte viability and suppressed inflammation and extracellular matrix degradation. CONCLUSION: Acetaminophen affects inflammatory factors secretion and extracellular matrix synthesis of human chondrocytes by regulating RNA N6-methyladenosine level and N6-methyladenosine-related protein expression. Stimulation of the normal chondrocyte cell line C28/I2 with the cytokine IL-1ß (10 µM) mimics the inflammatory state in vitro. Acetaminophen (Ace, 50 µg/mL) changes the m6A related proteins expression and the total RNA m6A levels in IL-1ß-treated chondrocyte cells. Furthermore, regulation of RNA m6A levels (by methylation inhibitor Cyc and/or Ace) affects IL-1ß-induced inflammatory cytokines secretion and extracellular matrix synthesis in C28/I2 cells.

Need for anti-tuberculosis treatment in patients with latent tuberculosis infection who undergo arthroplasty: a case report.

Background: It is currently estimated that about 1/3 of the global population is infected with mycobacterium tuberculosis (TB), and about 90% of those infected have asymptomatic latent infections. It has been reported that 85-90% of newly diagnosed active TB cases evolve from patients with latent tuberculosis infection (LTBI). In approximately 5-10% of patients, LTBI progresses to active TB during their lifetime. The number of artificial arthroplasty procedures performed is increasing. The vast majority of people undergoing arthroplasty are aged 60 years and older. Aging and surgical trauma can reduce the ability of the body to fight infection, which can also promote the recurrence of old or dormant TB infections. TB has been reported to reoccur in LTBI patients after arthroplasty who do not receive anti-TB treatment. This article reports the case of an elderly female patient with LTBI and knee osteoarthritis who underwent total knee arthroplasty and achieved good clinical results with anti-TB drug treatment. There is a lack of guidelines for the treatment of patients with LTBI undergoing artificial arthroplasty. This article attempts to provide a time-based treatment approach to reduce the recurrence of LTBI based on a literature review. Case Description: Based on a detailed history, a physical examination, and ancillary examinations, this 71-year-old female patient was found to have no active TB; however, after a positive ɣ-interferon release assay (IGRA) for TB infection, she was diagnosed with LTBI. She underwent artificial knee arthroplasty to treat osteoarthritis of the right knee. Anti-TB drugs were administered 2 weeks after the surgery, and good clinical results were achieved at the 53-month post-operative follow-up with no recurrence of TB. Conclusions: Patients with LTBI who undergo artificial arthroplasty require anti-TB treatment to reduce the risk of TB recurrence.

Pelvic height planning versus conventional templating in preoperative planning of acetabulum cup size for THA.

This study aimed to compare the accuracy of pelvic height planning vs. the conventional templating method for acetabulum cup measurement. A total of 200 consecutive patients undergoing primary total hip arthroplasty (THA) were randomly grouped as follows: group A, accepting conventional templating; group B, accepting pelvic height planning. Preoperative measurement of the acetabular cup was performed with conventional templating and pelvic height planning, respectively. There were 57 cases with the same size or with one type size discrepancy, 49 with two type size discrepancies, and 14 with three type size discrepancies in group A. There were 145 cases with the same size or one type size discrepancy, 20 with two type size discrepancies, and 3 type size discrepancies in group B. The mean difference between the planned size and actual cup size was 2.58 ± 0.89 mm (group A) vs. 1.38 ± 1.22 mm (group B). Therefore, pelvic height planning is reliable for use in preoperative planning compared with conventional templating.

Triptolide reduces the viability of osteosarcoma cells by reducing MKP-1 and Hsp70 expression.

Osteosarcoma is the most common type of malignant bone tumor found in adolescents and young adults. The aim of the present study was to determine whether triptolide, a diterpene epoxide extracted from the Tripterygium plant, was able effectively decrease the viability of osteosarcoma cells. The underlying molecular mechanisms are also investigated. The human osteosarcoma cell lines U-2 OS and MG-63 were used in this study. The U-2 OS and MG-63 cells were treated with 0, 5, 10, 25 or 50 nM triptolide. Cells treated with dimethyl sulfoxide only were used as the no drug treatment control. A commercial MTT kit was used to determine the effects of triptolide on cells. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is frequently overexpressed in tumor tissues, possibly related to the failure of a number of chemotherapeutics. Heat shock protein 70 (Hsp70) is a chaperone molecule that is able to increase drug resistance. The protein expression levels of MKP-1 and Hsp70 were determined using western blot analysis. The results indicate that triptolide effectively reduced the viability of the osteosarcoma cells. Furthermore, triptolide was found to effectively reduce MKP-1 expression and Hsp70 levels. Further analysis showed that triptolide reduced MKP-1 mRNA expression in the U-2 OS and MG-63 cells. Triptolide reduced Hsp70 mRNA expression levels in U-2 OS and MG-63 cells. These results suggest that triptolide effectively decreases the viability of osteosarcoma cells. These effects may be associated with the decreased expression of MKP-1 and Hsp70 levels. These results suggest that triptolide may be used in the treatments of osteosarcoma.

Therapeutic effect of lymphokine-activated killer cells treated with low-dose ionizing radiation on osteosarcoma.

The aim of the present study was to investigate the effect of lymphokine-activated killer (LAK) cells, which received low-dose ionizing radiation, on the treatment of osteosarcoma in rats. The cultured UMR-106 cells were inoculated under the anterior chest skin of 24 rats to establish an osteosarcoma model. In addition, the LAK cells from 24 mice were exposed to doses of 0 (control group), 0.65 or 3.25 mGy X-ray radiation. The tritiated thymidine (3H-TdR) release method and Winn assay were performed to determine the antitumor effects of the LAK cells. The proliferation of the mouse LAK cells treated with 3.25 mGy radiation was significantly higher than that for those treated with 0 or 0.65 mGy radiation, which suggested that low-dose ionizing radiation stimulates the proliferation of LAK cells. The tumor-bearing rats were divided into three groups and injected with LAK cells that had already received 0, 0.65 or 3.25 mGy radiation. The mean survival time of the 3.25-mGy group was longer than that of the 0- and 0.65-mGy groups. After 30 days, tumors with weights of ~6.25 and 2.0 g were identified in the rats of the 0- and 0.65-mGy groups, respectively. However, tumor proliferation was not detectable in the rats of the 3.25-mGy radiation group. Therefore, low-dose ionizing radiation effectively kills osteosarcoma cells in rats by stimulating the proliferation and enhancing the cytotoxicity of LAK cells.

A canine model of osteonecrosis of the femoral head induced by MRI guided argon helium cryotherapy system.

OBJECTIVE: This study is to identify the reliability of osteonecrosis of the femoral head (ONFH) modeling established by MRI guided argon helium cryotherapy system in beagles. METHODS: A total of 15 beagles were used to establish the ONFH model. The left femoral heads of the beagles received two cycles of argon helium freezing-thawing under MRI guidance and were considered as experimental group while the right femoral heads received only one cycle of argon helium freezing-thawing and were considered as the control group. X-ray, MRI, general shape and histological examinations were performed so as to identify the effect of modeling. RESULTS: At 4 week after modeling, MRI showed obvious bilateral hip joint effusion and marked femoral head bone marrow high signal. At 8 week after surgery, abnormal signal appeared in bilateral femoral heads. T1WI showed irregular patchy low signal, T2WI showed irregular mixed signals and the joint capsule effusion showed long T1 and T2 changes. Twelve weeks after operation, T1WI showed a low signal strip with clear boundary and T2WI showed intermediate signal. The changes of the left femoral heads were significant while compared with those of the right sides. The lacunae rates of femoral heads in the experimental group at 4, 8, and 12 week after surgery (40.75 ± 3.77, 57.46 ± 4.01, 50.27 ± 2.98) were higher than those in control group (30.08 ± 3.61, 49.43 ± 2.82, 40.56 ± 2.73). CONCLUSION: Canine model of ONFH was successfully established using an argon helium cryotherapy system.

Construction of tissue-engineered bone using a bioreactor and platelet-rich plasma.

The aim of the present study was to construct tissue-engineered bone using a bioreactor and platelet-rich plasma (PRP). Bone marrow mesenchymal stem cells (BMSCs) and ß-tricalcium phosphate (ß-TCP) were cultured in a perfusion bioreactor with PRP-containing medium for 21 days to form a BMSC-TCP composite. Rabbits were then implanted with the BMSC-TCP composite. The morphology of the implanted BMSC-TCP composite was observed three months after surgery by scanning electron microscopy and hematoxylin and eosin (H&E) staining. In addition, the expression of cluster of differentiation (CD)31 and von Willebrand factor (WF) in the implanted BMSC-TCP composite was detected using immunohistochemistry. Bone formation was determined by comprehensive testing Following culture in a perfusion bioreactor and PRP, the BMSCs adhered to the ß-TCP scaffold and the secretion of extracellular matrix was observed. The spreading and proliferation of cells was found to be enhanced on the scaffold. Furthermore, the vascular endothelial cell markers CD31 and VEF, were positively expressed. Therefore, these results suggest that tissue-engineered bone may be constructed using a bioreactor and PRP. PRP, which contains multiple growth factors, may promote vascularization of tissue-engineered bone.

A novel animal model of osteonecrosis of the femoral head induced using a magnetic resonance imaging-guided argon-helium cryotherapy system.

The aim of the present study was to establish a novel animal model of osteonecrosis of the femoral head (ONFH) using a magnetic resonance imaging (MRI)-guided argon-helium cryotherapy system. A total of 48 rabbits were used to generate the ONFH models. In group I, the left femoral head of the rabbits received two cycles of argon-helium freezing-thawing under MRI guidance, while in group II, the right femoral head of each rabbit received only one cycle of argon-helium freezing-thawing. X-ray and histological examinations were performed. The percentages of lacunae in the femoral heads of group I at weeks 4, 8 and 12 following surgery (49.75±3.17, 62.06±4.12 and 48.25±2.76%, respectively) were higher than those in group II (39.13±4.48, 50.69±3.84 and 37.50±3.86%, respectively). In addition, the percentage of empty lacunae in group I was 62.06% at week 8 following surgery. Therefore, an animal model of ONFH was successfully established using an argon-helium cryotherapy system. The percentage of empty lacunae in group I was higher than that in group II at weeks 4, 8 and 12 after surgery.