Osteosarcoma (OS) is the most common primary malignant bone sarcoma mainly affecting adolescents and young adults, which often progresses to pulmonary metastasis and leads to the death of OS patients. OS is characterized as a highly heterogeneous cancer type and the underlying pathologic mechanisms triggering tumor progress and metastasis are incompletely recognized. Surgery combined with neoadjuvant and postoperative chemotherapy has elevated 5-year survival to over 70% for patients with localized OS tumors, as opposed to only 20% of patients with recurrence and/or metastasis. Therefore, novel therapeutic strategies are needed to overcome the drawbacks of conventional treatments. Immunotherapy is gaining momentum for the treatment of OS with an increasing number of FDA-approved therapies for malignancies resistant to conventional therapies. Here, we review the OS tumor microenvironment and appraise the promising immunotherapies available in the management of OS.
Objective: Lianhua Qingwen combined with Western medicine (LHQW+WM) has been proposed as a viable treatment for coronavirus disease 2019 . Interestingly, umbrella reviews of systematic reviews (SRs), which provide the most comprehensive evidence, are the best evidence in evidence-based medicine. Therefore, an umbrella review of SRs that summarizes and evaluates the efficacy of LHQW+WM for COVID-19 is urgently required.Methods: Overall, 6 databases were used to conduct a comprehensive literature search from inception to January 22, 2022. The corrected covered area (CCA) was used to analyze the overlapping between SRs. Meta-analysis was conducted when that of the included SRs was inappropriate. A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2) was also employed to assess the quality of the included SRs.Results: In total, 12 SRs were identified, which included 12 unique primary studies. The included SRs ranged in quality from moderate to critically low and had an extremely high CCA (36.4%). Compared to conventional treatment, LHQW+WM showed efficacy concerning fatigue recovery [risk ratio (RR) = 1.69, 95% confidence interval (CI): 1.04-2.73, n = 2, I 2 = 0%], cough recovery (RR = 1.65, 95% CI: 1.09-2.51, n = 3, I 2 = 39.1%), and overall effective rates (RR = 1.17, 95% CI: 1.07-1.28, n = 3, I 2 = 17.5%).Conclusion: LHQW+WM may improve the clinical symptoms of patients with COVID-19; however, the results should be interpreted cautiously because of the rigorous processes in the included SRs.
Thyroid cancer (TC) is the most common type of endocrine cancer. Over the last 50 years, the global incidence of TC has been increasing. The survival rate of TC is higher than that of most other types of cancer, but it depends on numerous factors, including the specific type of TC and stage of the disease. Circular RNAs (circRNAs) are a new class of long noncoding RNA with a closed loop structure that have a critical role in the complex gene regulatory network that controls the emergence of TC. The most important function of circRNAs is their ability to specifically bind to microRNAs. In addition, the biological functions of circRNAs also include interactions with proteins, regulation of the transcription of genes and acting as translation templates. Based on the characteristics of circRNAs, they have been identified as potential biomarkers for the diagnosis of tumors. In the present review, the function and significance of circRNAs and their potential clinical implications for TC were summarized. Furthermore, possible treatment approaches involving the use of mesenchymal stem cells (MSCs) and exosomes derived from MSCs as carriers to load and transport circRNAs were discussed.
Ischemic stroke can induce rapid activation of the microglia. It has been reported that the microglia's survival is dependent on colony-stimulating factor 1 receptor (CSF1R) signaling and that pharmacological inhibition of CSF1R leads to morphological changes in the microglia in the healthy brain. However, the impact of CSF1R inhibition on neuronal structures and motor ability after ischemia-reperfusion remains unclear. In this study, we investigated microglial de-ramification, proliferation, and activation after inhibition of CSF1R by a tyrosine kinase inhibitor (ki20227) in a mouse model of global cerebral ischemia induced by bilateral common carotid artery ligation (BCAL). In addition to microglial morphology, we evaluated the mRNA expression of cytokines, chemokines, and inflammatory receptors. Our results show that pharmacological inhibition of CSF1R in ischemic mice resulted in the blockade of microglial proliferation and a shift in microglial morphology reflected by excessive de-ramification and a more activated phenotype accompanied by an enhanced innate immune response. Furthermore, we show that pharmacological inhibition of CSF1R in ischemic mice resulted in the aggravation of neuronal degeneration and behavioral impairment. Intravital two-photon imaging revealed that although pharmacological inhibition of CSF1R did not affect the recovery of dendritic structures, it caused a significant increase in spine elimination during reperfusion in ischemic mice. These findings suggest that pharmacological inhibition of CSF1R induces a blockade of microglial proliferation and causes acute activation of the microglia accompanied by a severe inflammatory response. It aggravates neuronal degeneration, loss of dendritic spines, and behavioral deficits after transient global cerebral ischemia.
Osteoarthritis (OA) is one of the most common chronic joint diseases and is gradually becoming the main cause of disability and joint pain in the elderly worldwide. Pyroptosis is a regulated programmed cell death triggered by inflammasomes. It leads to cell swelling, lysis, and bioactive molecule secretion. Studies found that the damaged chondrocytes in OA joints had morphological characteristics of pyroptosis, and the cytokines associated with pyroptosis in synovial fluid increased, indicating that pyroptosis may have certain impacts on the pathological progression of OA. This review briefly summarizes the molecular mechanisms of pyroptosis and the epidemiology and pathogenesis of OA. Furthermore, we discussed the role of pyroptosis in articular cartilage and synovium during OA and reviewed the progress of pyroptosis-related molecules in the targeted therapy of OA joints, hoping to provide feasible directions for the diversified treatment of OA.
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