Patient-derived xenograft models in musculoskeletal malignancies.

Successful oncological drug development for bone and soft tissue sarcoma is grossly stagnating. A major obstacle in this process is the lack of appropriate animal models recapitulating the complexity and heterogeneity of musculoskeletal malignancies, resulting in poor efficiency in translating the findings of basic research to clinical applications. In recent years, patient-derived xenograft (PDX) models generated by directly engrafting patient-derived tumor fragments into immunocompromised mice have recaptured the attention of many researchers due to their properties of retaining the principle histopathology, biological behaviors, and molecular and genetic characteristics of the original tumor, showing promising future in both basic and clinical studies of bone and soft tissue sarcoma. Despite several limitations including low take rate and long take time in PDX generation, deficient immune system and heterologous tumor microenvironment of the host, PDXs offer a more advantageous platform for preclinical drug screening, biomarker identification and clinical therapeutic decision guiding. Here, we provide a timely review of the establishment and applications of PDX models for musculoskeletal malignancies and discuss current challenges and future directions of this approach.

Folding of SAM-II riboswitch explored by replica-exchange molecular dynamics simulation.

Riboswitches are cis-acting RNA fragments that function via a conformational transition mechanism when a specific target molecule binds to its binding pocket, representing an inviting new class of biomolecular target for the development of antibiotics. To understand the folding mechanism of SAM-II riboswitch, occurring predominantly in proteobacteria, a 100ns replica-exchange molecular dynamics simulation in explicit solvent is performed. Our results show that this RNA pseudoknot has multiple folding pathways, and various intermediate structures. The resultant riboswitch conformational transition map is well consistent with the recent fluorescence measurement, which confirms the dynamical properties of this pseudoknot. Moreover, a novel transition pathway is predicted. The global folding dynamics is mainly coupled with the helix rather than the loop region. The potential folding pathways of the riboswitch presented here should lead to a deeper understanding of the folding mechanism of the riboswitch, as well as the conformational change of RNA pseudoknot.

Bibliometric Analysis of Global Research on Circular RNA: Current Status and Future Directions.

Circular RNAs (circRNAs) have gained significant attention in recent years. This bibliometric analysis aimed to provide insights into the current state and future trends of global circRNA research. The scientific output on circRNAs from 2010 to 2022 was retrieved from the Web of Science Core Collection with circRNA-related terms as the subjects. Key bibliometric indicators were calculated and evaluated using CiteSpace. A total of 7385 studies on circRNAs were identified. The output and citation number have increased rapidly after 2015. China, the USA, and Germany were top three publishing countries. Currently, circCDR1as, circHIPK3, circPVT1, circSHPRH, and circZNF609 are the most studied circRNAs; and all are related to cancer. The theme of research have shifted from transcript, exon circularization and miRNA sponge topics to the transcriptome, tumor suppressor, and biomarkers, indicating that research interests have evolved from basic to applied research. CircRNAs will continue to be a highly active research area in the near future. From the current understanding of circRNA characterization and regulatory mechanisms as miRNA sponges in cancer, future directions may examine potential diagnostic and therapeutic roles of circRNAs in cancers or the function and mechanism of circRNAs in other diseases.

Intelligent Algorithm-Based Ultrasound Images in Evaluation of Therapeutic Effects of Radiofrequency Ablation for Liver Tumor and Analysis on Risk Factors of Postoperative Infection.

This research aimed to explore the therapeutic effects of radiofrequency ablation (RFA) for liver tumors and to investigate the postoperative infection factors. Specifically, 80 patients with liver tumors undergoing ultrasound-guided FRA were selected as research subjects. They were diagnosed in the hospital. An intelligent fitting (IF) algorithm was compared with a genetic algorithm (GA) and applied to the RFA of the 80 patients. It was found that the running time of the IF algorithm was about 0.2 times than that of the GA, demonstrating better global searching capabilities. The mean diameter of single liver tumors was (3.45 ± 1.24) cm, and the complete ablation rate of tumors with diameters less than 3 cm was 87.88%, that of tumors with diameters of 3-5 cm was 72.92%, and that of tumors with a diameter of more than 5 cm was 63.33%. Posttreatment, the AST level decreased significantly and the ALB level increased significantly, and the difference was notable (P < 0.05P<); the TBIL level (36.8 ± 9.7 umol/L) was lower than prior treatment (17.9 ± 8.5 umol/L) and the ALT level (45.2 ± 6.8 g/L) was lower than prior treatment (19.6 ± 5.7 g/L), showing a notable difference (P < 0.05P<). The diameter, whether there was great vessel invasion, and TNM staging were associated with infection after RFA, and the difference was notable. The ultrasound images can effectively evaluate the therapeutic effects of RFA and the degree of inactivation of liver tumors. In addition, the tumor stage was an independent risk factor for postoperative infection.

Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia.

Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. (1)H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine.

mTOR: An attractive therapeutic target for osteosarcoma?

Osteosarcoma (OS) is a common primary malignant bone tumor with high morbidity and mortality in children and young adults. How to improve poor prognosis of OS due to resistance to chemotherapy remains a challenge. Recently, growing findings show activation of mammalian target of rapamycin (mTOR), is associated with OS cell growth, proliferation, metastasis. Targeting mTOR may be a promising therapeutic approach for treating OS. This review summarizes the roles of mTOR pathway in OS and present research status of mTOR inhibitors in the context of OS. In addition, we have attempted to discuss how to design a better treatment project for OS by combining mTOR inhibitor with other drugs.

Nampt/Visfatin/PBEF: a functionally multi-faceted protein with a pivotal role in malignant tumors.

Nampt/Visfatin/PBEF is a primary, rate-limiting enzyme involved in NAD+ biosynthesis, which serves as a pivotal substance for proteins, and is required for cell growth, survival, DNA replication and repair and energy metabolism. Growing researches have elucidated that it is a pleiotropic protein that functions not only as an enzyme, but also as an adipocytokin, a growth factor, and a cytokine. Additionally, accumulated evidences indicate that Nampt is correlated to various malignant tumors, and complicated mechanisms are proposed to be involved in the carcinogenesis, progression, invasion and metastasis of it, including regulation of energy metabolism and genome instability, promotion of proliferation, angiogenesis, and tumor-promoting inflammation, resistance in cell death and avoidance of immune destruction. APO866 and CHS-828 are recognized inhibitors of Nampt, known to block the intracellular and extracellular NAD+ synthesis pathway. Both of them are currently in clinical trials for the treatment of various malignant tumors and have been shown to represent novel promising antitumor chemotherapeutic agents.