Cross-talk between circRNAs and m6A modifications in solid tumors.

Circular RNAs (circRNAs) possess unique biological properties and distribution characteristics that enable a variety of biological functions. N6-methyladenosine (m6A), a prevalent epigenetic modification in organisms, is regulated by factors including methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). These factors play critical roles in various pathophysiological processes. There is growing evidence that m6A modifications are common within circRNAs, affecting their synthesis, translation, translocation, degradation, and stability. Additionally, circRNAs regulate biological processes that influence m6A modifications. This review explores the metabolism and functions of m6A modifications and circRNAs, their interactions, and their specific regulatory mechanisms in different tumors, offering insights into m6A-circRNA interaction in cancer.

Mechanism and clinical value of exosomes and exosomal contents in regulating solid tumor radiosensitivity.

Radiotherapy is among the routine treatment options for malignant tumors. And it damages DNA and other cellular organelles in target cells by using ionizing radiation produced by various rays, killing the cells. In recent years, multiple studies have demonstrated that exosomes are mechanistically involved in regulating tumor formation, development, invasion and metastasis, and immune evasion. The latest research shows that radiation can affect the abundance and composition of exosomes as well as cell-to-cell communication. In the environment, exosome-carried miRNAs, circRNA, mRNA, and proteins are differentially expressed in cancer cells, while these molecules play a role in numerous biological processes, including the regulation of oncogene expression, mediation of signaling pathways in cancer cells, remodeling of tumor-related fibroblasts, regulation of cell radiosensitivity, and so forth. Therefore, elucidation of the mechanism underlying the role of exosomes in radiotherapy of malignant tumors is crucial for improving the efficacy of radiotherapy. This review will summarize the research advances in radiosensitivity of malignant tumors related to exosomes.

Mechanism and Function of Circular RNA in Regulating Solid Tumor Radiosensitivity.

Radiotherapy is an important tool in the treatment of malignant tumors, and exploring how to make radiotherapy more effective is a new way to break through the current bottleneck in the development of radiation oncology. Circular RNAs (circRNAs) are a special class of endogenous non-coding RNAs. Numerous studies have shown that circRNAs have shown great potential in regulating the biological functions of tumors, including proliferation, migration, invasion, and treatment resistance, and that differences in their expression levels are closely related to the clinical prognosis of tumor patients. This review systematically compares the mechanisms of circRNAs in the process of tumor development and radiosensitivity and provides insight into the clinical translation of circRNAs in radiotherapy.

CircNEIL3 promotes cervical cancer cell proliferation by adsorbing miR-137 and upregulating KLF12.

BACKGROUND: CircRNAs play crucial roles in multiple tumours. However, the functions of most circRNAs in cervical cancer remain unclear. METHODS: This study collected GSE113696 data from the GEO database to search for differentially expressed circRNAs in cervical cancer. Quantitative reverse transcription PCR was used to detect the expression level of circNEIL3 in cervical cancer cells and tissues. Then, functional experiments in vitro and in vivo were performed to evaluate the effects of circNEIL3 in cervical cancer. RESULTS: CircNEIL3 was highly expressed in cervical cancer. In vivo and in vitro experiments verified that circNEIL3 enhanced the proliferation capacity of cervical cancer cells. RNA immunoprecipitation, luciferase reporter assay, pull-down assay, and fluorescent in situ hybridization confirmed the interaction between circNEIL3 and miR-137 in cervical cancer. A luciferase reporter assay showed that circNEIL3 adsorbed miR-137 and upregulated KLF12 to regulate the proliferation of cervical cancer cells. CONCLUSIONS: CircNEIL3 is an oncogene in cervical cancer and might serve as a ceRNA that competitively binds to miR-137, thereby indirectly upregulating the expression of KLF12 and promoting the proliferation of cervical cancer cells.

MicroRNA-621 Acts as a Tumor Radiosensitizer by Directly Targeting SETDB1 in Hepatocellular Carcinoma.

Radiotherapy is one of the most important treatment methods of tumors. However, the application of radiotherapy in hepatocellular carcinoma (HCC) is limited due to the low tolerance of normal liver cells for radiation and inherent radiation resistance in HCC. With the in-depth study of microRNAs (miRNAs) in tumor therapy, the regulation of tumor radiosensitivity by miRNAs has been a research hotspot in recent years. In the present study, the expression of miR-621 was lower in HCC tissues and cells, and such low expression of miR-621 was associated with poor prognosis in HCC patients. In addition, in vivo and in vitro assays confirmed that the high expression of miR-621 could significantly enhance the radiosensitivity of HCC. Moreover, the expressions of miR-621 and SETDB1 in HCC tissues were negatively correlated. Dual-luciferase reporter assays indicated that miR-621 could directly target the 3' UTR of SETDB1. In addition, miR-621 enhanced the radiosensitivity of HCC cells via directly inhibiting SETDB1. Besides, the miR-621 and/or SETDB1 axis improved the radiosensitivity of HCC cells via activating the p53-signaling pathway. Taken together, miR-621 and/or SETDB1 might be used as a novel therapeutic target for the treatment of HCC.

Evaluating the Prognostic Value of microRNA-203 in Solid Tumors Based on a Meta-Analysis and the Cancer Genome Atlas (TCGA) Datasets.

BACKGROUND: It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA) datasets. METHODS: By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016), we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. RESULTS: 33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn't predict poor overall survival (OS) and progression-free survival (PFS) in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR)=1.81, 95% confidence intervals (CI) 1.31-2.49; P<0.001), pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001) and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001); but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040) and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001). Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. CONCLUSION: Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer.

Prognostic role of tissue and circulating microRNA-200c in malignant tumors: a systematic review and meta-analysis.

BACKGROUND: Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic review and meta-analysis to evaluate the prognostic role of miR-200c expression in different cancers. METHODS: Studies were recruited by searching PubMed, Embase and the Cochrane Library (last search update was May 2014) and assessed by further quality evaluation. RESULTS: A total of 25 studies dealing with various carcinomas were identified for systematic review. Among them, 18 studies were ultimately included in the meta-analysis. Our results indicated that the expression of tissue miR-200c was not associated with OS and PFS in various carcinomas; however, downregulation of tissue miR-200c did predict poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001). Furthermore, overexpression of blood miR-200c was significantly related to poor OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001, respectively), especially in patients with advanced disease. CONCLUSION: This systematic review and meta-analysis clarified that low expression of miR-200c in primary tissue was significantly associated with poor survival in cancer patients at early stage, whereas a high level of blood miR-200c predicted poor prognosis in patients with advanced tumors.

Frameless stereotactic body radiation therapy for multiple lung metastases.

Two patients with multiple lung metastases (≥ 5) were treated using frameless stereotactic body radiation therapy (SBRT) on an Elekta Axesse linear accelerator equipped with an interdigitation-capable multileaf collimator and four-dimensional cone-beam CT (4D CBCT). The technique and the early clinical outcomes were evaluated. Patient A with five lung metastases and Patient B with seven lung metastases underwent SBRT (48 Gy/8 fractions for Patient A, 42 Gy/7 fractions for Patient B). The treatments were administered using a 6 MV photon beam. The nominal dose rate was 660 MUs/min. Patients were positioned and immobilized using thermoplastic masks and image guidance was done using 4D CBCT. The targets were delineated on the images of the 4D CT, and the positron emission tomography-computed tomography (PET-CT) images were taken as references. A two-step, volumetric-modulated arc therapy (VMAT) plan was designed for each patient. Step 1: the lesions in one lung were irradiated by a 210° arc field; Step 2: the rest of the lesions in the other lung were irradiated by a 120° arc field. Plans were evaluated using conformity index (CI) and homogeneity index (HI). Patients were followed up and adverse events were graded according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0). The beam-on time of each treatment was less than 10 min. The CI and HI for the two plans were 0.562, 0.0709 and 0.513, 0.0794, respectively. Pulmonary function deteriorated slightly in both patients, and the patient with seven lung lesions was confirmed to have Grade 1 radiation pneumonitis. The technique was fast, accurate, and well tolerated by patients, and the two-step plan is a helpful design in reducing the dose to the lungs.

The roles of exosomes in esophageal cancer.

The incidence and mortality rate of esophageal cancer (EC) are higher worldwide. Exosomes are nanoscale vesicles derived from various types of cells, exhibiting a stable presence in bodily fluids, and contain a plethora of bioactive components including proteins, DNA, and RNA. Exosomes can mediate cell-to-cell communication and signaling. Numerous studies conducted both domestically and internationally have indicated the significant involvement of exosomes in tumor development and their potential as novel diagnostic and prognostic biomarkers for liquid biopsy. This review seeks to consolidate the role of exosomes and bioactive substances in the progression of EC and elaborate on the opportunities and challenges associated with the clinical application of exosomes in EC.

Hsa_circ_0004776 regulates the retina neovascularization in progression of diabetic retinopathy via hsa-miR-382-5p/BDNF axis.

The aim of this work was to identify the regulatory function of hsa_circ_0004776 in the progression of diabetic retinopathy (DR). The direct interactions between hsa_circ_0004776 and hsa-miR-382-5p and between hsa-miR-382-5p and BDNF, were confirmed via dual-luciferase reporter assays. Quantitative Real-Time PCR analysis indicated that hsa_circ_0004776 was highly expressed in aqueous humour samples of DR patients and human retinal microvascular epithelial cells (hRECs) under a high-glucose environment, whereas hsa-miR-382-5p showed the opposite trend. Overexpressed hsa_circ_0004776 significantly enhanced DNA synthesis, proliferation, migration, and tube formation in hRECs in hyperglycaemia, while hsa-miR-382-5p mimics reversed these changes. Additionally, in a streptozotocin-induced Sprague-Dawley rat model of DR, vitreous microinjection of rno-miR-382-5p agomir reversed the pathologic features in the progression of DR, including retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis. Our results indicated that under hyperglycaemic conditions, hsa_circ_0004776 influences the progression of DR via hsa-miR-382-5p and thus represents a potential therapeutic target.

Comparative phenotypic and transcriptomic analysis reveals genotypic differences in nitrogen use efficiency in sorghum.

Sorghum (Sorghumbicolor L.), a model for C4 grass and an emerging biofuel crop, is known for its robust tolerance to low input field. However, the focus on enhancing nitrogen use efficiency (NUE) in sorghum under low nitrogen (N) conditions has been limited. This study conducted hydroponic experiments and field trials with two sorghum inbred lines, contrasting in their N efficiency: the N-efficient (398B) and the N-inefficient (CS3541) inbred lines. The aim was to analyze the key factors influencing NUE by integrating phenotypic, physiological, and multi-omics approaches under N deficiency conditions. The field experiments revealed that 398B displayed superior NUE and yield performance compared to CS3541. In hydroponic experiments, the growth of 398B outperformed CS3541 following N deficiency, attributing to its higher photosynthetic and sustaining activity of N metabolism-related enzymes. Genomic and transcriptomic integration highlighted fewer genomic diversities and alterations in global gene expression in 398B, which were likely contributor to its high NUE. Additionally, co-expression network analysis suggested the involvement of key genes which impact N uptake efficiency (NUpE) and N utilization efficiency (NUtE) in both lines, such as an N transporter, Sobic.003G371000.v3.2leaf(NPF5.10) and a transcription factor, Sobic.002G202800.v3.2leaf(WRKY) in bolstering NUE under low-N stress. The findings collectively suggested that 398B achieved higher NUpE and NUtE, effectively coordinating photosynthesis and N metabolism to enhance NUE. The candidate genes regulating N uptake and utilization efficiencies could provide valuable insights for developing sorghum breeds with improved NUE, contributing to sustainable agricultural practices and bioenergy crop development.

Expression of Glutathione Peroxidase4 in Patients with Esophageal Squamous Carcinoma and Its Impact on the Radiosensitivity of Esophageal Squamous Carcinoma.

OBJECTIVE: Glutathione peroxidase-4 (GPX4) is a member of Ferroptosis and lipid circulation. This study aims to investigate the expression of GPX4 in esophageal squamous cell carcinoma and its impact on radiosensitivity. METHOD: Immunohistochemistry staining was used to detect GPX4 expression in 180 samples of ESCC tissues and adjacent tissues. We analyzed the relationship between GPX4 expression and ESCC clinical parameters. In vitro experiments were conducted using apoptosis assays and colony formation assays to investigate the effect of GPX4 on the radiosensitivity of ESCC cells. In vivo experiments were carried out using a nude mouse xenograft model to evaluate the impact of GPX4 on the radiosensitivity of ESCC. RESULTS: GPX4 expression was lower in adjacent tissues than tumor tissues. The expression of GPX4 was significantly associated with the pathological grade of ESCC. The overall survival time (OS) of ESCC patients with low GPX4 expression was significantly longer than that of patients with high GPX4 expression. GPX4 could be used as independent prognostic factors in patients with ESCC. In vivo experiments, silencing of GPX4 or using GPX4 inhibitors significantly inhibits the viability and colony formation of ESCC cells after radiation exposure while increasing intracellular reactive oxygen species (ROS) levels, and significantly suppresses the tumorigenic ability of ESCC cells in subcutaneous xenografts after radiation exposure. CONCLUSION: GPX4 is highly expressed in ESCC, which has the potential value for prognostic assessment of ESCC. Silencing or inhibiting GPX4 can enhance the radiosensitivity of ESCC.

Tryptophan regulates sorghum root growth and enhances low nitrogen tolerance.

Over evolutionary time, plants have developed sophisticated regulatory mechanisms to adapt to fluctuating nitrogen (N) environments, ensuring that their growth is balanced with their responses to N stress. This study explored the potential of L-tryptophan (Trp) in regulating sorghum root growth under conditions of N limitation. Here, two distinct sorghum genotypes (low-N tolerance 398B and low-N sensitive CS3541) were utilized for investigating effect of low-N stress on root morphology and conducting a comparative transcriptomics analysis. Our foundings indicated that 398B exhibited longer roots, greater root dry weights, and a higher Trp content compared to CS3541 under low-N conditions. Furthermore, transcriptome analysis revealed substantial differences in gene expression profiles related to Trp pathway and carbon (C) and N metabolism pathways between the two genotypes. Additional experiments were conducted to assess the effects of exogenous Trp treatment on the interplay between sorghum root growth and low-N tolerance. Our observations showed that Trp-treated plants developed longer root and had elevated levels of Trp and IAA under low-N conditons. Concurrently, these plants demonstrated stronger physiological activities in C and N metabolism when subjected to low-N stress. These results underscored the pivotal role of Trp on root growth and low-N stress responses by balancing IAA levels and C and N metabolism. This study not only deepens our understanding of how plants maintain growth plasticity during environmental stress but also provides valuable insights into the availability of amino acid in crops, which could be instrumental in developing strategies for promoting crop resilience to N deficiency.

TDP-43 was Involved in Radiation-induced Neuronal Damage and May Not Through the BDNF/TrkB Pathway.

Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), ß-tubulin and dendritic spines were decreased. In the irradiated neurons, the ß-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. These data indicate that TDP-43 is involved in radiation-induced neuronal synaptic plasticity decline and developmental damage, furthermore, the BDNF/TrkB signaling pathway may not be involved in this process.

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma: A randomized, multicenter, phase III clinical trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. METHODS: This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. RESULTS: The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. CONCLUSIONS: IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

The therapeutic targets of N6-methyladenosine (m6A) modifications on tumor radioresistance.

Radiation therapy is an important tool for malignant tumors, and its tolerance needs to be addressed. In recent years, several studies have shown that regulators of aberrant m6A methylation play an important role in the formation, development and invasion and metastasis of tumors. A large number of studies have confirmed aberrant m6A methylation as a new target for tumour therapy, but research on whether it can play a role in tumor sensitivity to radiotherapy has not been extensive and thorough enough. Recent studies have shown that all three major enzymes of m6A methylation have significant roles in radioresistance, and that the enzymes that play a role differ in different tumor types and by different mechanisms, including regulating tumor cell stemness, affecting DNA damage and repair, and controlling the cell cycle. Therefore, elucidating the mechanisms of m6A methylation in the radiotherapy of malignant tumors is essential to counteract radioresistance, improve the efficacy of radiotherapy, and even propose targeted treatment plans for specific tumors. The latest research progress on m6A methylation and radioresistance is reviewed in this article.

Immunotherapy combined with radiotherapy to reverse immunosuppression in microsatellite stable colorectal cancer.

In recent years, the exploration of immune checkpoint inhibitors (ICIs) has resulted in substantial progress and has changed the pattern of cancer treatment. ICIs have revolutionized the treatment landscape of microsatellite instable colorectal cancer while the efficacy is very limited in patients with microsatellite stable colorectal cancer. Therefore, sensitizing MSS CRC to immunotherapy is a major challenge in the field of CRC immunotherapy. Immunotherapy-based combination therapy is an effective strategy. This review of radiotherapy (RT) as a local treatment has dramatically changed in recent years, and it is now widely accepted that RT can deeply reshape the tumor environment by modulating the immune response. Such evidence gives a strong rationale for the synergism of radiotherapy and immunotherapy, introducing the era of 'immunoradiotherapy'. How to give full play to the synergistic effect of radiotherapy and immunotherapy to improve the therapeutic effect of MSS CRC and bring good prognosis is a hot problem to be solved in the field of cancer treatment.This article reviews the development of CRC immunotherapy, the immune resistance mechanism of MSS CRC, and the impact and potential value of immunotherapy combined with radiotherapy on the immune environment of CRC.

The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.

Radiotherapy, a treatment method employing radiation to eradicate tumor cells and subsequently reduce or eliminate tumor masses, is widely applied in the management of numerous patients with tumors. However, its therapeutic effectiveness is somewhat constrained by various drug-resistant factors. Recent studies have highlighted the ubiquitination/deubiquitination system, a reversible molecular modification pathway, for its dual role in influencing tumor behaviors. It can either promote or inhibit tumor progression, impacting tumor proliferation, migration, invasion, and associated therapeutic resistance. Consequently, delving into the potential mechanisms through which ubiquitination and deubiquitination systems modulate the response to radiotherapy in malignant tumors holds paramount significance in augmenting its efficacy. In this paper, we comprehensively examine the strides made in research and the pertinent mechanisms of ubiquitination and deubiquitination systems in governing radiotherapy resistance in tumors. This underscores the potential for developing diverse radiosensitizers targeting distinct mechanisms, with the aim of enhancing the effectiveness of radiotherapy.

The hsa_circ_0004805/hsa_miR-149-5p/TGFB2 axis plays critical roles in the pathophysiology of diabetic retinopathy in vitro and in vivo.

The aim of this study was to investigate the mechanism underlying the role of a recently identified hsa_circ_0004805/hsa_miR-149-5p/transforming growth factor beta 2 (TGFB2) axis in the progression of diabetic retinopathy (DR). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis suggested that hsa_circ_0004805 was highly expressed in aqueous humor samples of patients with DR, whereas hsa_miR-149-5p showed the opposite trend. Meanwhile, the results of a dual-luciferase reporter assay indicated that hsa_miR-149-5p directly interacted with both hsa_circ_0004805 and TGFB2. Using a variety of assays (Cell Counting Kit-8, EdU-labeling, Transwell, flow cytometric, wound healing, tube formation assays), we found that the overexpression of hsa_circ_0004805 significantly downregulated the level of hsa_miR-149-5p and promoted DNA synthesis, proliferation, migration, and tube formation in human retinal microvascular epithelial cells (hRECs) cultivated in a high-glucose environment. In contrast, hsa_miR-149-5p mimics inhibited DNA synthesis, proliferation, migration, and tube formation in hRECs by reducing the expression of its downstream target TGFB2 as well as the levels of phosphorylated SMAD2; however, these effects were reversed by the overexpression of hsa_circ_0004805. In a streptozotocin-induced Sprague-Dawley rat model of DR, retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis were evident, which could be reversed by vitreous microinjection of rat miR-149-5p mimics (rno-miR-149-5p agomir). Combined, our findings indicated that, under hyperglycemia, the hsa_circ_0004805/hsa_miR-149-5p/TGFB2 axis plays a critical role in the retinal pathophysiology associated with the development of DR, and has potential as a therapeutic target in the treatment of this condition.

Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Pain Relief for Bone Metastases: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to investigate the difference in pain relief between stereotactic body radiation therapy (SBRT) and conventional radiation therapy (cRT) for patients with bone metastases. METHODS AND MATERIALS: Clinical trials and observational studies comparing SBRT versus cRT for bone metastases were retrieved. The main endpoint was pain relief after radiation therapy; the secondary endpoints were pain score change, local progression-free survival, reirradiation rate, and toxic events. When there was a significant heterogeneity, the random-effects model was applied. Otherwise, the fixed-effects model was used. Analyses of all included studies were performed first, followed by analyses of randomized controlled trials (RCTs) only. RESULTS: Six RCTs, 1 prospective cohort study, and 3 retrospective observational studies were enrolled. Between 2004 and 2019, 448 patients received SBRT, and 445 patients received cRT. All prospective studies defined the lesions as oligometastatic. Pooled results based on all included studies indicated that SBRT was generally associated with a higher overall relief rate (P < .001 at 3 months; P = .015 at 6 months) and complete relief rate (P = .029 at 1 month; P < .001 at 6 months). Pooled results based on RCTs indicated that at 3 and 6 months, SBRT was associated with a higher overall relief rate (P < .001 and P = .017, respectively) and complete relief rate (P < .001 and P < .00, respectively). Subgroup analyses indicated that in more cases, the analgesic advantage of SBRT was more obvious when spinal lesions were irradiated, when the difference in the mean biological effective dose (BED) was less, or when intensity modulated radiation therapy was used to deliver SBRT. CONCLUSIONS: Excessive elevation of BED introduces the risk of diminishing the analgesic effect of SBRT. SBRT delivered using intensity modulated radiation therapy is preferred for pain relief in spinal oligometastases. More RCTs are required to determine the most appropriate BED or dose regimen for SBRT.