AP2a-Mediated Upregulation of miR-125a-5p Ameliorates Radiation-Induced Oxidative Stress Injury via BRD4/Nrf2/HO-1 Signaling.

Radiation therapy is widely used to restrain tumor progression, but it is always accompanied by damage to healthy tissues. We aimed to probe the impact and mechanism of activator protein 2a (AP2a) and miR-125a-5p in radiation-induced oxidative stress injury. Human umbilical vein endothelial cells (HUVECs) were treated with X rays to induce radiation injury in vitro. Cell viability was measured using MTT assays. Flow cytometry assay was employed to detect the apoptosis rate. Oxidative stress markers were evaluated by detection kits. Gene or protein levels were determined by RT-qPCR or Western blotting. Validation of the interaction of miR-125a-5p with BRD4 and AP2a was conducted by dual luciferase assay or ChIP. MiR-125a-5p and AP2a were decreased in irradiated HUVECs, whereas BRD4 was increased. MiR-125a-5p overexpression or BRD4 silencing alleviated the cell viability decline, apoptosis, and oxidative stress injury caused by radiation treatment. MiR-125a-5p repressed the BRD4 level. The protective effects of miR-125a-5p overexpression in the radiation-induced oxidative injury were impeded by BRD4 overexpression. Moreover, AP2a bound to the promoter of miR-125a-5p. MiR-125a-5p inhibition reversed the effects of AP2a overexpression on radiational oxidative injury by modulating Nrf2/HO-1 signaling. AP2a transcriptionally activated miR-125a-5p ameliorated oxidative stress injury of HUVECs caused by radiation through Nrf2/HO-1 signaling.

A rare lymphoplasmacyte-rich meningioma involving the dura of the skull base and cervical spinal cord: A case report.

Lymphoplasmacyte-rich meningioma (LPRM) is a rare subtype of meningioma, the specific pathogenesis of which remains unclear. Herein, we report the case of a 48-year-old Asian man who experienced progressive deafness and limb weakness. Magnetic resonance imaging revealed extramedullary masses diffusely growing, wrapping, and compressing the cervical spinal cord. The dural lesion was partially excised by surgery, and postoperative pathological examination confirmed the diagnosis of LPRM. Diffuse LPRM is extremely rare, and its treatment is challenging owing to difficulties associated with surgery and the uncertain efficacy of traditional therapies. Therefore, further clinical practice and basic research are needed to improve the prognosis of diffuse LPRM.

Identification of a pyroptosis-related prognosis gene signature and its relationship with an immune microenvironment in gliomas.

BACKGROUND: Glioma is the most common type of primary brain cancer, and the prognosis of most patients with glioma is poor. Pyroptosis is a newly discovered inflammatory programmed cell death. However, the expression of pyroptosis-related genes (PRGs) in glioma and its correlation with prognosis are unclear. METHODS: 27 pyroptosis genes differentially expressed between glioma and adjacent normal tissues were identified. All glioma cases could be stratified into 2 subtypes based on these differentially expressed PRGs. The prognostic value of each PRG was evaluated to construct a prognostic model. RESULTS: A novel 16-gene signature was constructed by using the least absolute shrinkage and selection operator Cox regression method. Then, patients with glioma were divided into low- and high-risk groups in the TCGA cohort. The survival rate of patients in the low-risk group was significantly higher than that in the high-risk group (P = .001). Patients with glioma from the Gene Expression Omnibus (GEO) cohort were stratified into 2 risk groups by using the median risk score. The overall survival (OS) of the low-risk group was longer than that of the high-risk group (P = .001). The risk score was considered an independent prognostic factor of the OS of patients with glioma. Gene ontology and Kyoto Encylopedia of Genes and Genomes analysis showed that the differentially expressed PRGs were mainly related to neutrophil activation involved in immune responses, focal adhesion, cell cycle, and p53 signaling pathway. CONCLUSION: PRGs could predict the prognosis of glioma and play significant roles in a tumor immune microenvironment.

LncRNA DLGAP1-AS2 promotes the radioresistance of rectal cancer stem cells by upregulating CD151 expression via E2F1.

BACKGROUND: Radiotherapy resistance is one of the major causes of rectal cancer treatment failure. LncRNA DLGAP1-AS2 participates in the progression of several cancers. We explored the role and potential mechanism of DLGAP1-AS2 in the radioresistance of rectal cancer stem cells. METHODS: HR8348-R cells, radioresistant cells from HR8348 after irradiation, were isolated into CD133 negative (CD133-) and positive (CD133+) cells. Cell proliferation, apoptosis, migration and tumorsphere formation were determined by CCK-8, flow cytometry, wound healing assay and tumorsphere formation assay, respectively. CD133, tumor stem cell drug resistance gene (MDR1 and BCRP1), DNA repair marker (γ-H2AX) and AKT/mTOR/cyclinD1 signaling were measured by Western blot. The relationship between DLGAP1-AS2 and E2F1 was verified using RIP. The interaction between E2F1 and CD151 promoter was confirmed using dual-luciferase reporter gene assay and ChIP. AKT inhibitor API-2 was employed for validating the effect of AKT/mTOR/cyclinD1 signaling in the radioresistance of rectal cancer cells. RESULTS: The DLGAP1-AS2 level was increased in CD133+ cells after irradiation. DLGAP1-AS2 knockdown inhibited the proliferation, migration and tumorsphere formation while stimulating apoptosis in CD133+ cells. DLGAP1-AS2 inhibition downregulated the expression of CD133, MDR1, BCRP1 and γ-H2AX and suppressed AKT/mTOR/cyclinD1 activation. DLGAP1-AS2 upregulated the expression of CD151 by interacting with E2F1. API-2 neutralized the promotive effects of overexpressed CD151 on radioresistance. CONCLUSION: DLGAP1-AS2 accelerates the radioresistance of rectal cancer cells through interactions with E2F1 to upregulate CD151 expression via the activation of the AKT/mTOR/cyclinD1 pathway.

Impact of molecular subtypes on metastatic behavior and overall survival in patients with metastatic breast cancer: A single-center study combined with a large cohort study based on the Surveillance, Epidemiology and End Results database.

Breast cancer is a highly heterogeneous disease at the molecular level and >90% of mortalities are due to metastasis and its associated complications. The present study determined the impact of molecular subtypes on metastatic behavior and overall survival (OS) of patients with metastatic breast cancer. The influence of molecular subtypes on the sites and number of metastases in 166 patients with metastatic breast cancer from a single center were assessed; and the influence of molecular subtypes on the sites and number of metastases and OS in 15,322 metastatic cases among 329,770 patients with primary breast cancer from the Surveillance, Epidemiology and End Results database were assessed. Analysis of both datasets revealed that different molecular subtypes exhibited differences in the prevalence of different metastatic sites and number of metastases. A larger proportion of bone metastasis was observed in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ subtype than in other subtypes, more lung metastasis was observed in the HR-/HER2+ subtype and more liver metastasis occurred in the HR+/HER2+ and HR-/HER2+ subtypes. Single-site metastasis was more common for the HR+/HER2- subtype than in other subtypes, while 2-3 sites of metastases were more common for the HR+/HER2+ subtype and ≥4 sites of metastases were more frequent in the HR-/HER2+ and HR-/HER2- subtypes. The mean OS of patients with primary breast cancer in the HR+/HER2- subtype group was the longest (78.5 months), while the HR-/HER2- group had the shortest mean OS (69.1 months). The mean OS of the metastatic HR+/HER2+ group was the longest (46.0 months), while the mean OS of the metastatic HR-/HER2- group was the shortest (18.5 months). In conclusion, the results of the present study suggested that different molecular subtypes of breast cancer have different metastatic behavior, as well as mean OS.

A RBC membrane-camouflaged biomimetic nanoplatform for enhanced chemo-photothermal therapy of cervical cancer.

Due to the untargeted release of chemical drugs, the efficacy of chemotherapy is often compromised along with serious side effects on patients. Recently, the development of targeted delivery systems using nanomaterials as carriers has provided more alternatives for chemical drug transportation. In this study, we developed a novel targeted nanocomplex of GOQD-ICG-DOX@RBCM-FA NPs (GID@RF NPs). First, PEG modified graphene oxide quantum dots (GOQDs) were used to co-load the photosensitizer of indocyanine green (ICG) and DOX, to form GOQD-ICG-DOX NPs (GID NPs). Then, the red blood cell membrane (RBCM) was applied for GID NP camouflage to avoid immune clearance. Finally, folic acid was used to endow the targeting ability of GID@RF NPs. MTT assay showed that the survival rate of HeLa cells reduced by 71% after treatment with GID@RF NPs and laser irradiation. Meanwhile, membrane camouflage significantly prolonged the blood circulation time and enhanced the immune evading ability of GID NPs. Moreover, the drug accumulation at tumor sites was significantly improved through the strong interaction between FA and FA receptor highly expressed on the tumor cells. In vivo assay demonstrated the strongest tumor growth inhibition ability of the combinational chemo/photothermal therapy. H&E analysis indicated no significant abnormalities in the major organs of mice undergoing GID@RF NPs treatment. The level of blood and biochemical parameters remained stable as compared to the control. In summary, this combinational therapy system provides a safe, rapid and effective alternative for the treatment of cervical cancer in the future.

Increased miR-323a induces bladder cancer cell apoptosis by suppressing c-Met.

The current study aimed to evaluate the expression and role of miR-323a in the progression of bladder cancer (BC), thereby providing a theoretical basis and potential therapy methods for BC patients. Our data showed that miR-323a levels were significantly reduced in BC tissues compared with those of non-cancerous tissues. Meanwhile, miR-323a was significantly decreased in human BC cell lines (T24, J82, TCCSUP, RT-112) than that in human normal bladder epithelial cell line SV-HUC-1. Furthermore, inhibition of miR-323a markedly enhanced the migration and invasive capacity of T24 and TCCSUP cells. Moreover, overexpression of miR-323a significantly prompted the apoptosis of BC cells. Dual luciferase reporter assay and western blot analysis confirmed that c-Met was a target gene of miR-323a. More importantly, upregulation of c-Met significantly prompted BC cell proliferation mainly as a result of the enhanced level of phosphorylation of AKT. This effect could be abolished when c-Met was silenced in BC cells. In summary, reduced miR-323a expression in BC contributed to enhanced BC cell proliferation and migration mainly by targeting c-Met.

X-ray repair cross-complementing group 1 Arg399Gln gene polymorphism and susceptibility to colorectal cancer:a meta-analysis.

X-ray repair cross-complementing group 1 (XRCC1), a DNA repair enzyme, plays a crucial role in the base excision repair by generating a single nucleotide repair patch. It has been demonstrated that the XRCC1 Arg399Gln gene polymorphism was associated with variations in XRCC1 enzyme activity. The aim of this study was to quantitatively summarize the association between the XRCC1 Arg399Gln polymorphism and susceptibility to colorectal cancer (CRC). A comprehensive search of the PubMed, Embase, and China National Knowledge Infrastructure databases was conducted for studies on the association between the XRCC1 Arg399Gln polymorphism and CRC risk. Summary odds ratio (OR) with its corresponding 95 % confidence interval (95 %CI) was estimated, in a fixed-effects model or a random-effects model when appropriate, to assess the association. Totally, 26 case-control studies with 6,979 cases and 11,470 controls were included into this meta-analysis. The pooled results of total studies showed that the XRCC1 Arg399Gln polymorphism was significantly associated with increased risk of CRC in all genetic contrast models (OR(A vs. G) = 1.13, 95 %CI 1.03-1.23, P (OR) = 0.008; OR(Gln/Gln vs. Arg/Arg) = 1.24, 95 %CI 1.04-1.46, P (OR) = 0.015; OR(Gln/Gln vs. Arg/Gln + Arg/Arg) = 1.19, 95 %CI 1.03-1.38, P (OR) = 0.021; OR(Gln/Gln + Arg/Gln vs. Arg/Arg) = 1.14, 95 %CI 1.02-1.28, P (OR) = 0.022), except for the additive contrast model (OR(Arg/Gln vs. Arg/Arg) = 1.11, 95 %CI 0.99-1.25, P (OR) = 0.064). The statistically significant association between the XRCC1 Arg399Gln polymorphism and CRC risk was observed among studies with high quality and in Asians, but not in Caucasians. Sensitivity analyses by sequential omission of any individual studies further identified the significant association. Publication bias was inexistent in this meta-analysis. The meta-analysis suggests that the XRCC1 Arg399Gln polymorphism is associated with increased risk of CRC.

[Effects of 2A-1-1 on the aggregation and Ca2+ influx of platelets].

OBJECTIVE: To explore the effects of 2A-1-1 (purified component from Panax notoginsengs saponins) on the aggregation of and Ca2+ influx into human platelets. METHODS: The aggregation of platelets was tested by nephelometry, Fura-2 fluorescent technique was used for detecting cell [Ca2+]i. The effects of 2A-1-1, nifedipine and SK&F96365 on Ca(2+) influx into human platelets induced by ADP or CPA were observed separately. RESULTS: Nifedipine (< 20 micromol/L) could not inhibit platelet aggregation induced by ADP or the Ca(2+) influx induced by ADP or CPA. SK&F96365 at 20 micromol/L could inhibit the maximal aggregation of platelets induced by ADP with a inhibitory rate of 59.83%, at 15 micromol/L could inhibit the Ca2+ influx induced by CPA or ADP. 2A-1-1 (5, 10 and 20 micromol/L) could inhibit the maximal aggregation of platelets induced by ADP with the inhibitory rates of 47.06%, 53.47% and 71.52%, respectively. 2A-1-1 at 10 and 20 micromol/L could inhibit the Ca2+ influx induced by CPA or ADP. CONCLUSIONS: 2A-1-1 can inhibit platelets aggregation, block the ROC (Receptor-dependent Ca2+ channels) and inhibit Ca2+ influx of human platelets.