PSMA2 promotes glioma proliferation and migration via EMT.

BACKGROUND: Gliomas advance rapidly and are associated with a poor prognosis. Epithelial-mesenchymal transition (EMT) accelerates the progression of gliomas, exerting a pivotal role in glioma development. Proteasome subunit alpha type-2 (PSMA2) exhibits high expression levels in gliomas. however, its specific involvement in glioma progression and its correlation with EMT remain elusive. This study aims to elucidate the role of PSMA2 in glioma progression and its potential association with EMT. METHODS: Online tools were employed to analyze the expression patterns and survival curves of PSMA2 in gliomas. The relationship between PSMA2 and various characteristics of glioma patients was investigated using data from the TCGA and CGGA databases. In vitro, cell proliferation and migration were assessed through CCK-8, colony formation, and transwell assays. Furthermore, a tumor xenograft model in nude mice was established to evaluate in vivo tumorigenesis. Protein binding to PSMA2 was scrutinized using co-immunoprecipitation MS (co-IP MS). The potential biological functions and molecular pathways associated with PSMA2 were explored through GO analysis and KEGG analysis, and the correlation between PSMA2 and EMT was validated through correlation analysis and Western blot experiments. RESULTS: Bioinformatics analysis revealed a significant upregulation of PSMA2 across various cancers, with particularly heightened expression in gliomas. Moreover, elevated PSMA2 levels were correlated with advanced tumor stages and diminished survival rates among glioma patients. Inhibition of PSMA2 demonstrated a pronounced suppressive effect on glioma cell proliferation, both in vitro and in vivo. Knockdown of PSMA2 also impeded the migratory capacity of glioma cells. GO and KEGG enrichment analyses indicated that PSMA2-binding proteins (identified through Co-IP-MS) were associated with cell adhesion molecule binding and cadherin binding. Western blot results further confirmed the role of PSMA2 in promoting epithelial-mesenchymal transition (EMT) in glioma cells. CONCLUSION: Our study provides evidence supporting the role of PSMA2 as a regulatory factor in EMT and suggests its potential as a prognostic biomarker for glioma progression.

A network meta-analysis on the effects of different exercise types on COPD patients.

Objective: This study aimed to compare and rank the effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in chronic obstructive pulmonary disease (COPD) by network meta-analysis (NMA).Methods: PubMed, Cochrane, Embase, and Web of Science were searched to identify randomized controlled trials investigating the effects of exercise training on COPD. The search period began on the date of database establishment and ended in April 8, 2023. Two reviewers independently screened the retrieved articles, extracted relevant data, and assessed the risk of bias in the included studies. NMA was performed using Stata 15.1 and R 4.2.1.Results: This study included a total of 27 studies involving 1415 patients. The NMA findings indicated that HIIT was the most effective intervention for improving 6-Minute Walk Distance (6MWD) with a SUCRA (Surface Under the Cumulative Ranking) score of 87.68%. In addition, HIIT showed the highest efficacy in improving Forced Expiratory Volume in 1 second (FEV1) with a SUCRA score of 73.17%, FEV1/FVC% with a SUCRA score of 79.52%, and St. George's Respiratory Questionnaire (SGRQ) score with a SUCRA score of 73.88%. Conversely, ET was found to be the most effective for ameliorating Forced Vital Capacity (FVC) with a SUCRA score of 73.39%.Conclusion: The findings of this study suggest that HIIT may be more effective than endurance exercise, resistance exercise, and AE in improving the 6MWD, FEV1, FEV1/FVC ratio, and SGRQ scores in patients with COPD. Additionally, ET may be better than resistance exercise, AE, and HIIT in improving FVC in COPD patients. However, due to the limited number of studies conducted on HIIT, more high-quality randomized controlled trials (RCTs) are required to verify these conclusions.

MSFF-Net: Multi-Stream Feature Fusion Network for surface electromyography gesture recognition.

In the field of surface electromyography (sEMG) gesture recognition, how to improve recognition accuracy has been a research hotspot. The rapid development of deep learning provides a new solution to this problem. At present, the main applications of deep learning for sEMG gesture feature extraction are based on convolutional neural network (CNN) structures to capture spatial morphological information of the multichannel sEMG or based on long short-term memory network (LSTM) to extract time-dependent information of the single-channel sEMG. However, there are few methods to comprehensively consider the distribution area of the sEMG signal acquisition electrode sensor and the arrangement of the sEMG signal morphological features and electrode spatial features. In this paper, a novel multi-stream feature fusion network (MSFF-Net) model is proposed for sEMG gesture recognition. The model adopts a divide-and-conquer strategy to learn the relationship between different muscle regions and specific gestures. Firstly, a multi-stream convolutional neural network (Multi-stream CNN) and a convolutional block attention module integrated with a resblock (ResCBAM) are used to extract multi-dimensional spatial features from signal morphology, electrode space, and feature map space. Then the learned multi-view depth features are fused by a view aggregation network consisting of an early fusion network and a late fusion network. The results of all subjects and gesture movement validation experiments in the sEMG signal acquired from 12 sensors provided by NinaPro's DB2 and DB4 sub-databases show that the proposed model in this paper has better performance in terms of gesture recognition accuracy compared with the existing models.

Long non-coding RNA DDX11-AS1 promotes the proliferation and migration of glioma cells by combining with HNRNPC.

Glioma is a malignant tumor of the central nervous system with complex pathogenesis, difficult operation, and a high postoperative recurrence rate. At present, there is still a lack of effective treatment. Long non-coding RNA DDX11 antisense RNA 1 (DDX11-AS1) has been shown to promote tumor development, such as hepatocellular carcinoma, esophageal cancer, etc. However, its molecular mechanism in glioma is poorly understood. In this study, we found that the expression of DDX11-AS1 was elevated in glioma tissues, and patients with high expression of DDX11-AS1 had poor prognosis. DDX11-AS1 was a potential prognostic marker. Functionally, DDX11-AS1 promoted glioma cell proliferation and migration. Mechanistically, DDX11-AS1 interacted with RNA-binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) to promote Wnt/ß-catenin and AKT pathways and the epithelial-mesenchymal transition process. In summary, our study manifests that the DDX11-AS1/HNRNPC axis may play a vital part in the occurrence and development of glioma, which provides new ideas and therapeutic targets for the diagnosis, treatment, and prognosis of glioma.

Identification and Validation of an Endoplasmic Reticulum Stress-Related lncRNA Signature for Colon Adenocarcinoma Patients.

Purpose: Endoplasmic reticulum (ER) stress has a significant effect on cancer cells. Increasing numbers of studies indicate that long non-coding RNAs (lncRNAs) promote the development of colon adenocarcinoma (COAD), but the relationship between ER stress-related lncRNAs and the prognosis of COAD remains unclear. The aim of the current study was to construct and validate an ER stress-related lncRNA prognostic signature to predict COAD prognoses. Methods: Gene expression data and clinical information from the Cancer Genome Atlas and the Gene Expression Omnibus with COAD were downloaded and analyzed. Cox regression and least absolute shrinkage and selection operator regression were then used to develop an ER stress-related lncRNA signature. COAD patients were then divided into high-risk and low-risk groups based on the median risk score to analyze prognoses. Tumor mutation burdens (TMBs) and the differences in copy number variations (CNVs) between the two groups were also analyzed. Lastly, gene set enrichment analysis (GSEA) was used to explore the enrichment pathways and biological processes associated with differentially expressed genes in the high-risk and low-risk groups, and lncRNA expression in the model was validated via quantitative real-time PCR in colon cancer and paracancerous tissues. Results: A signature including 8 ER stress-related lncRNAs was constructed. COAD prognoses were significantly poorer in the high-risk group than in the low-risk group. There were few differences in TMBs and CNVs between the two groups. In GSEA analysis, in the high-risk group highly expressed genes associated with extracellular matrix pathways were significantly enriched. Conclusion: The 8-ER stress-related lncRNA derived from the present study is a potential indicator of COAD prognosis.

APMAP Promotes Epithelial-Mesenchymal Transition and Metastasis of Cervical Cancer Cells by Activating the Wnt/ß-catenin Pathway.

Cervical cancer is a malignant tumor of the female reproductive system. At present, its occurrence, development and transfer mechanism are not entirely clear. APMAP (Adipocyte Plasma Membrane Associated Protein) is a glycosyl type II transmembrane protein that is mainly distributed in the plasma membrane and endoplasmic reticulum of adipocytes. APMAP has been reported to be involved in lipid transport and can induce epithelial-mesenchymal transition of prostate cancer and the liver metastasis of colorectal cancer. However, the role of APMAP in cervical cancer is still unknown. We analyzed the expression and prognosis of APMAP using data in both the GEO and the TCGA databases. We analyzed the function of APMAP using Transwell, wound healing assay and flow cytometry, and assessed the main mechanisms of APMAP by RT-PCR and Western blotting. We found that APMAP was highly expressed in cervical cancer tissues, and patients with high expression had poor prognosis. The functional in vitro experiments demonstrated that APMAP knockdown significantly inhibited the migration ability of cervical cancer cells, but had little effect on cell apoptosis. Mechanically, APMAP promotes cervical cancer cell migration and epithelial-mesenchymal transition by activating the Wnt/ß-catenin pathway. Overall, APMAP is a potential prognostic marker as well as a therapeutic target of cervical cancer.

A Novel Inflammatory lncRNAs Prognostic Signature for Predicting the Prognosis of Low-Grade Glioma Patients.

BACKGROUND: As immunotherapy has received attention as new treatments for brain cancer, the role of inflammation in the process of glioma is of particular importance. Increasing studies have further shown that long non-coding RNAs (lncRNAs) are important factors that promote the development of glioma. However, the relationship between inflammation-related lncRNAs and the prognosis of glioma patients remains unclear. The purpose of this study is to construct and validate an inflammation-related lncRNA prognostic signature to predict the prognosis of low-grade glioma patients. METHODS: By downloading and analyzing the gene expression data and clinical information of the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) patients with low-grade gliomas, we could screen for inflammatory gene-related lncRNAs. Furthermore, through Cox and the Least Absolute Shrinkage and Selection Operator regression analyses, we established a risk model and divided patients into high- and low-risk groups based on the median value of the risk score to analyze the prognosis. In addition, we analyzed the tumor mutation burden (TMB) between the two groups based on somatic mutation data, and explored the difference in copy number variations (CNVs) based on the GISTIC algorithm. Finally, we used the MCPCounter algorithm to study the relationship between the risk model and immune cell infiltration, and used gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the enrichment pathways and biological processes of differentially expressed genes between the high- and low-risk groups. RESULTS: A novel prognostic signature was constructed including 11 inflammatory lncRNAs. This risk model could be an independent prognostic predictor. The patients in the high-risk group had a poor prognosis. There were significant differences in TMB and CNVs for patients in the high- and low-risk groups. In the high-risk group, the immune system was activated more significantly, and the expression of immune checkpoint-related genes was also higher. The GSEA, GO, and KEGG analyses showed that highly expressed genes in the high-risk group were enriched in immune-related processes, while lowly expressed genes were enriched in neuromodulation processes. CONCLUSION: The risk model of 11 inflammation-related lncRNAs can serve as a promising prognostic biomarker for low-grade gliomas patients.

ACTL6A knockdown inhibits cell migration by suppressing the AKT signaling pathway and enhances the sensitivity of glioma cells to temozolomide.

Molecular-targeted therapy has had a significant impact on glioma. Notably, actin-like 6A (ACTL6A) has been indicated to be essential for embryonic development and tumor progression. However, the role of ACTL6A in glioma remains unclear. The present study aimed to investigate the effects of ACTL6A on glioma cell migration and sensitivity to temozolomide (TMZ). The expression levels of ACTL6A were analyzed in patients with glioma, and survival curves were created using data from The Cancer Genome Atlas. U251 and T98G cells were transfected with short hairpin (sh)RNA for use in loss-of-function experiments to investigate the biological function and molecular mechanisms of ACTL6A. Furthermore, an MTT assay was used to assess the effect of ACTL6A on the sensitivity of glioma cells to TMZ. The results demonstrated that ACTL6A was expressed at higher levels in glioma tissues compared with normal brain tissues. Furthermore, high expression of ACTL6A was associated with a poor prognosis. The knockdown of ACTL6A significantly inhibited the migration phenotype in glioma cells and significantly decreased the levels of phosphorylated AKT in glioma cells. The AKT signaling activator SC79 partly attenuated the inhibitory effects of ACTL6A shRNA on glioma cell migration. Additionally, the knockdown of ACTL6A enhanced the sensitivity of glioma cells to TMZ. In conclusion, these results suggest that ACTL6A knockdown inhibited the migration of human glioma cells, at least in part through inactivation of the AKT signaling pathway, and increased the sensitivity of glioma cells to TMZ. Therefore, ACTL6A may be a potential therapeutic target for glioma.

GALNT6 Knockdown Inhibits the Proliferation and Migration of Colorectal Cancer Cells and Increases the Sensitivity of Cancer Cells to 5-FU.

The incidence of colorectal cancer (CRC) is increasing annually worldwide, highlighting the need for novel therapeutics to be developed. GALNT6 is a member of the N-acetylgalactosyltransferase enzyme family, which exhibits oncogenic functions in several types of cancers, such as breast cancer and ovarian cancer. However, the function of GALNT6 in CRC has not received much attention in recent years and is therefore poorly understood. In this study, the GALNT6 gene was screened using RNA-seq data obtained from The Cancer Genome Atlas (TCGA). RNA-seq data from 50 pairs of matched CRC patients in TCGA were obtained and analyzed, and the protein expression levels of GALNT6 were verified in 10 pairs of clinical samples. These samples showed that GALNT6 was highly expressed in CRC tissues. Functional analysis also showed that GALNT6 knockdown inhibited the proliferation and migration of CRC cells and increased the number of apoptotic cells. Furthermore, GALNT6 knockdown suppressed tumor growth in vivo. GALNT6 also regulated the AKT pathway based on ingenuity pathway analysis and western blotting assay. Finally, GALNT6 knockdown was observed to increase the sensitivity of CRC cells to 5-Fluorouracil (5-FU). These results, taken together, show that GALNT6 knockdown inhibits proliferation and migration of CRC cells and increases cellular sensitivity to 5-FU. It is therefore possible that targeting GALNT6 might prove to be an effective avenue for exploration in any attempt to develop new therapies for the treatment of CRC.

A seven-gene signature model predicts overall survival in kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a potentially fatal urogenital disease. It is a major cause of renal cell carcinoma and is often associated with late diagnosis and poor treatment outcomes. More evidence is emerging that genetic models can be used to predict the prognosis of KIRC. This study aimed to develop a model for predicting the overall survival of KIRC patients. RESULTS: We identified 333 differentially expressed genes (DEGs) between KIRC and normal tissues from the Gene Expression Omnibus (GEO) database. We randomly divided 591 cases from The Cancer Genome Atlas (TCGA) into training and internal testing sets. In the training set, we used univariate Cox regression analysis to retrieve the survival-related DEGs and futher used multivariate Cox regression with the LASSO penalty to identify potential prognostic genes. A seven-gene signature was identified that included APOLD1, C9orf66, G6PC, PPP1R1A, CNN1G, TIMP1, and TUBB2B. The seven-gene signature was evaluated in the training set, internal testing set, and external validation using data from the ICGC database. The Kaplan-Meier analysis showed that the high risk group had a significantly shorter overall survival time than the low risk group in the training, testing, and ICGC datasets. ROC analysis showed that the model had a high performance with an AUC of 0.738 in the training set, 0.706 in the internal testing set, and 0.656 in the ICGC external validation set. CONCLUSION: Our findings show that a seven-gene signature can serve as an independent biomarker for predicting prognosis in KIRC patients.

Lnc GNG12-AS1 knockdown suppresses glioma progression through the AKT/GSK-3ß/ß-catenin pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly being regarded as regulators of glioma development. Notably, some studies report that GNG12-AS1 plays important functions and molecular mechanism in breast cancer, but there are no existing studies in glioma. OBJECTIVE: To analyze the biological functions and potential mechanisms of GNG12-AS1 in glioma. METHODS: We detected the expression of GNG12-AS1 in glioma tissues through analyzing TCGA data as well as our clinical samples. We then evaluated cell proliferation through MTT assay and colony formation and cell migration by transwell assay, wound healing assay and single cell tracking assay. After, we analyzed the effects of the AKT/GSK-3ß/ß-catenin through Western blotting and utilized the ß-catenin agonist SKL2001 for the rescue experiment. RESULTS: GNG12-AS1 was highly expressed in glioma tissues. The silence of GNG12-AS1 inhibited the proliferation, migration and epithelial-mesenchymal transition of glioma cells, and reduced the activity of the AKT/GSK-3ß/ß-catenin pathway. Notably, SKL2001 could reverse cell migration as well as ß-catenin expression in glioma cells with lower GNG12-AS1 expression. CONCLUSIONS: GNG12-AS1 regulates proliferation and migration of glioma cells through the AKT/GSK-3ß/ß-catenin signaling and can perhaps be a new target for the treatment of glioma.

The miR-145 rs353291 C allele increases susceptibility to atherosclerosis.

Atherosclerosis (AS) is one of the leading causes of death, with variable frequencies in different populations. To this end, we examined whether AS is associated with the miR-145 rs353291 polymorphism and specific rs353291 alleles. The distribution of the rs353291 C allele and CC genotypes was significantly higher in AS patients than in controls. Compared to individuals with the rs353291 TT genotype, carriers of the rs353291 C allele showed a significant increase in the plasma levels of sCD40L, IL-6 and MCP-1 and a decrease in miR-145 expression. After ox-LDL administration, the peripheral blood mononuclear cells (PBMCs) of rs353291 C allele carriers showed significantly increased CD40 and MCP-1 expression compared with those of individuals with the rs353291 TT genotype. These data suggest that the rs353291 C allele may increase susceptibility to atherosclerosis.

First case in China of vaccine-associated poliomyelitis after sequential Inactivated and bivalent oral polio vaccination.

A 16 week newborn vaccinated with bOPV 4 weeks after his first routine IPV vaccination. Nineteen days later, asymmetrical paralysis was developed on his legs, and it was diagnosed to be VAPP. Perianal abscess is suspected to be a risk factor based on some limited results of retrospective studies in China. This is a risk factor similar to the multiple intramuscular injections found by researchers in last century. The two risk factors remind us that, apart from the routine infection route of the fecal to mouth and intestinal tract, skin injury (ulceration) exposure pathway should not be ignored as another possible way of causing polio, for the local injury and lesions of the skin may increase the possibility of oral poliovirus vaccine's entry into the body. As a result, to further reduce the incidence of VAPP, bOPV should be avoided for perianal abscess. If there is perianal abscess, skin injury, or if injection is unavoidable after bOPV vaccination of an infant, much attention should be paid to the treatment and cleaning of infant feces.

Resveratrol alleviates diabetic cardiomyopathy in rats by improving mitochondrial function through PGC-1α deacetylation.

Recent evidence shows that resveratrol (RSV) may ameliorate high-glucose-induced cardiac oxidative stress, mitochondrial dysfunction and myocardial fibrosis in diabetes. However, the mechanisms by which RSV regulates mitochondrial function in diabetic cardiomyopathy have not been fully elucidated. Mitochondrial dysfunction contributes to cardiac dysfunction in diabetic patients, which is associated with dysregulation of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). In this study we examined whether resveratrol alleviated cardiac dysfunction in diabetes by improving mitochondrial function via SIRT1-mediated PGC-1α deacetylation. T2DM was induced in rats by a high-fat diet combined with STZ injection. Diabetic rats were orally administered RSV (50 mg·kg-1·d-1) for 16 weeks. RSV administration significantly attenuated diabetes-induced cardiac dysfunction and hypertrophy evidenced by increasing ejection fraction (EF%), fraction shortening (FS%), ratio of early diastolic peak velocity (E velocity) and late diastolic peak velocity (A velocity) of the LV inflow (E/A ratio) and reducing expression levels of pro-hypertrophic markers ANP, BNP and ß-MHC. Furthermore, manganese superoxide dismutase (SOD) activity, ATP content, mitochondrial DNA copy number, mitochondrial membrane potential and the expression of nuclear respiration factor (NRF) were all significantly increased in diabetic hearts by RSV administration, whereas the levels of malondialdehvde (MDA) and uncoupling protein 2 (UCP2) were significantly decreased. Moreover, RSV administration significantly activated SIRT1 expression and increased PGC-1α deacetylation. H9c2 cells cultured in a high glucose (HG, 30 mmol/L) condition were used for further analyzing the role of SIRT1/PGC-1α pathway in RSV regulation of mitochondrial function. RSV (20 µmol/L) caused similar beneficial effects in HG-treated H9c2 cells in vitro as in diabetic rats, but these protective effects were abolished by addition of a SIRT1 inhibitor sirtinol (25 µmol/L) or by SIRT1 siRNA transfection. In H9c2 cells, RSV-induced PGC-1α deacetylation was dependent on SIRT1, which was also abolished by a SIRT1 inhibitor and SIRT1 siRNA transfection. Our results demonstrate that resveratrol attenuates cardiac injury in diabetic rats through regulation of mitochondrial function, which is mediated partly through SIRT1 activation and increased PGC-1α deacetylation.

Natural product ß-thujaplicin inhibits homologous recombination repair and sensitizes cancer cells to radiation therapy.

Investigation of natural products is an attractive strategy to identify novel compounds for cancer prevention and treatment. Numerous studies have shown the efficacy and safety of natural products, and they have been widely used as alternative treatments for a wide range of illnesses, including cancers. However, it remains unknown whether natural products affect homologous recombination (HR)-mediated DNA repair and whether these compounds can be used as sensitizers with minimal toxicity to improve patients' responses to radiation therapy, a mainstay of treatment for many human cancers. In this study, in order to systematically identify natural products with an inhibitory effect on HR repair, we developed a high-throughput image-based HR repair screening assay and screened a chemical library containing natural products. Among the most interesting of the candidate compounds identified from the screen was ß-thujaplicin, a bioactive compound isolated from the heart wood of plants in the Cupressaceae family, can significantly inhibit HR repair. We further demonstrated that ß-thujaplicin inhibits HR repair by reducing the recruitment of a key HR repair protein, Rad51, to DNA double-strand breaks. More importantly, our results showed that ß-thujaplicin can radiosensitize cancer cells. Additionally, ß-thujaplicin sensitizes cancer cells to PARP inhibitor in different cancer cell lines. Collectively, our findings for the first time identify natural compound ß-thujaplicin, which has a good biosafety profile, as a novel HR repair inhibitor with great potential to be translated into clinical applications as a sensitizer to DNA-damage-inducing treatment such as radiation and PARP inhibitor. In addition, our study provides proof of the principle that our robust high-throughput functional HR repair assay can be used for a large-scale screening system to identify novel natural products that regulate DNA repair and cellular responses to DNA damage-inducing treatments such as radiation therapy.

Effects of gene polymorphisms in the endoplasmic reticulum stress pathway on clinical outcomes of chemoradiotherapy in Chinese patients with nasopharyngeal carcinoma.

There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system. The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO. And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC). The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test, univariate and multivariate logistic regression analyses. We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients. CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy. And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression. In conclusion, SNPs of VCP rs2074549, CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.

Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells.

With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.

Association of the LOX-1 rs1050283 Polymorphism with Risk for Atherosclerotic Cerebral Infarction and its Effect on sLOX-1 and LOX-1 Expression in a Chinese Population.

AIMS: The interaction between lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1) and oxidized LDL (ox-LDL) has been viewed as an important pathogenic factor for cardiovascular diseases. This study aimed to explore the association of a functional polymorphism rs1050283 in the 3'-untranslated region of the LOX-1 gene with atherosclerotic cerebral infarction (ACI) susceptibility, and we also investigated the effects of the rs1050283 polymorphism on LOX-1 expression and serum levels of sLOX-1 in patients with ACI. METHODS: A case-controlled study was performed in 526 patients with ACI and 640 healthy controls. Genotyping was performed by DNA sequencing method. Real-time PCR and Western blotting were used to determine the level of LOX-1 expression. Serum levels of sLOX-1 were quantified using ELISA according to the manufacturer's instruction. RESULTS: The results of the present study showed that the frequency of rs1050283 T allele was significantly higher in patients with ACI than in healthy controls. We also found that the rs1050283 polymorphism T allele was associated with increased LOX-1 expression at mRNA and protein levels in patients with ACI. Furthermore, we also observed that among patients with ACI, those with the rs1050283 T allele showed an increased serum level of sLOX-1. CONCLUSION: Our research demonstrated that the rs1050283 T allele of LOX-1 is strongly associated with an increased risk for ACI in a Chinese population, which also affects levels of LOX-1 and sLOX-1.

miR-145 mediated the role of aspirin in resisting VSMCs proliferation and anti-inflammation through CD40.

BACKGROUND: Aspirin (ASA) is the most widely used medicine to prevent cardiovascular diseases; however, the mechanisms by which ASA exerts its anti-proliferative effect remain not fully understood. This study was designed to investigate whether miR-145 is involved in the regulation of vascular smooth muscle cells' (VSMCs) proliferation and to determine the anti-inflammatory effects of ASA via its regulation of CD40 to provide a new theoretical basis for the pharmacological effect of aspirin. METHODS: The TNF-α induced proliferation model of VSMCs was divided into different groups with or without aspirin. Cell proliferation was detected by EdU; Real-time PCR was used to detect the mRNA expression of miR-145, CD40, and Calponin, a VSMCs differentiation marker gene. Western blot was used to detect the protein expression of CD40; ELISA was used to determine the concentrations of the inflammatory cytokine IL-6 in cell supernatants. RESULTS: The proliferation of VSMCs was stimulated by TNF-α and accompanied by decreased levels of Calponin. TNF-α also decreased the levels of miR-145 and increased the levels of CD40 and IL-6. Pretreatment with 20 µg/mL of aspirin in VSMCs could partially block the above-mentioned effects induced by TNF-α. The protective effects of ASA in VSMCs were reversed by a pretreatment with a miR-145 inhibitor. We also found that the expression of miR-145 in peripheral blood mononuclear cells in ischemic stroke patients was significantly increased after a 10-day treatment with aspirin. CONCLUSION: miR-145 is involved in the anti-proliferation and anti-inflammation effects of aspirin on VSMCs by inhibiting the expression of CD40.