Fibronectin-1 modulated by the long noncoding RNA OIP5-AS1/miR-200b-3p axis contributes to doxorubicin resistance of osteosarcoma cells.

Chemoresistance has been an obstacle in the further improvement of 5-year survival rates of osteosarcoma (OS) patients, but the underlying mechanism of chemo-resistance remains unclear. A comprehensive analysis of mRNAs and noncoding RNAs related to OS chemo-resistance could help solve this problem. In the current study, we first identified that fibronectin-1 (FN1), screened by microarray analysis in three paired chemo-resistant and chemo-sensitive OS cell lines, was significantly upregulated in the chemo-resistant OS cell lines and tissues and was related to unfavourable prognosis. Further functional assays revealed that FN1 inhibition greatly increased the sensitivity of OS cells to doxorubicin in vitro and in vivo, whereas FN1 overexpression had the opposite effect. Moreover, mechanistic investigation demonstrated, by a series of assays that included luciferase reporter gene, RNA immunoprecipitation, RNA pull-down and rescue assays, that FN1 expression was regulated by the oncogenic long noncoding RNA (lncRNA) OIP5-AS1 through sponging miR-200b-3p. Thus, these results indicated the role and potential application of the lncRNA OIP5-AS1/miR-200b-3p/FN1 regulatory pathway as a promising target in treatment of OS chemo-resistance.

Composition and variation analysis of TCR ß-chain CDR3 repertoire in the thymus and spleen of MRL/lpr mouse at different ages.

T cells play an important role in the onset and progression of systemic lupus erythematosus (SLE), and the biases in T cell receptor beta variable (TRBV) region families and complementarity determining region three (CDR3) composition in SLE patients and mouse models have been widely reported. However, the relationship between the composition and variation in the TCR ß-chain CDR3 repertoire and SLE has not been established. Here, we compared and analyzed the thymic and splenic TCR ß-chain CDR3 mRNA sequences by Roche 454 high-throughput sequencing from MRL/lpr mice at different ages. Our results indicate that diversity in the TCR CDR3 repertoire from the thymus and spleen from MRL/lpr mouse was significantly decreased with increased age (disease progression) and showed a bias in usage of common TRBV and TRBJ families. The N1 region insertions in the highly expressed CDR3s significantly increased with disease progression. This study provides a new perspective for studying SLE with progression of disease in clonal level of TCR, which may provide a basis for studying the mechanism of the MRL/lpr autoreactive T cells response and tailor an individualized treatment targeting these T cells.

Research and experimental verification of lightweight loader rims.

The safety performance and structural stiffness of a rim, which is the main load-bearing structure of the loader during operation, influence the overall performance, stability, and braking capabilities of the machine. In the industry, researchers are currently pursuing lightweight and high-strength rims as a primary objective. A low weight not only enhances machinery fuel efficiency but also aligns with societal demands for sustainable development, energy conservation, and emission reduction. In this article, multiobjective optimization analysis on rims composed of three different materials is performed, and the relationships between various optimization parameters and target parameters are established using the results of response surface construction. Multiobjective genetic algorithms are utilized to derive various optimization plans, which are subsequently evaluated through static analysis, fatigue analysis, and weight loss analysis. The final optimization plan is determined based on the calculation results while considering production costs. Field tests are conducted on the optimized rims under various working conditions to verify the test results, evaluate the reliability of the finite element analysis results, and confirm the safety of the optimized rim.

Differentiation of high grade glioma and solitary brain metastases by measuring relative cerebral blood volume and fractional anisotropy: a systematic review and meta-analysis of MRI diagnostic test accuracy studies.

OBJECTIVE: This study aims to research the efficacy of MRI (I) for differentiating high-grade glioma (HGG) (P) with solitary brain metastasis (SBM) (C) by creating a combination of relative cerebral blood volume (rCBV) (O) and fractional anisotropy (FA) (O) in patients with intracerebral tumors. METHODS: Searches were conducted on September 2021 with no publication date restriction, using an electronic search for related articles published in English, from PubMed (1994 to September 2021), Scopus (1977 to September 2021), Web of Science (1985 to September 2021), and Cochrane (1997 to September 2021). A total of 1056 studies were found, with 23 used for qualitative and quantitative data synthesis. Inclusion criteria were: patients diagnosed with HGG and SBM without age, sex, or race restriction; MRI examination of rCBV and FA; reliable histopathological diagnostic method as the gold-standard for all conditions of interest; observational and clinical studies. Newcastle-Ottawa quality assessment Scale (NOS) and Cochrane risk of bias tool (ROB) for observational and clinical trial studies were managed to appraise the quality of individual studies included. Data extraction results were managed using Mendeley and Excel, pooling data synthesis was completed using the Review Manager 5.4 software with random effect model to discriminate HGG and SBM, and divided into four subgroups. RESULTS: There were 23 studies included with a total sample size of 597 HGG patients and 373 control groups/SBM. The analysis was categorized into four subgroups: (1) the subgroup with rCBV values in the central area of the tumor/intratumoral (399 HGG and 232 SBM) shows that HGG patients are not significantly different from SBM/controls group (SMD [95% CI] = -0.27 [-0.66, 0.13]), 2) the subgroup with rCBV values in the peritumoral area (452 HGG and 274 SBM) shows that HGG patients are significantly higher than SBM (SMD [95% CI] =  -1.23 [-1.45 to -1.01]), (3) the subgroup with FA values in the central area of the tumor (249 HGG and 156 SBM) shows that HGG patients are significantly higher than SBM (SMD [95% CI] = - 0.44 [-0.84,-0.04]), furthermore (4) the subgroup with FA values in the peritumoral area (261 HGG and 168 SBM) shows that the HGG patients are significantly higher than the SBM (SMD [95% CI] = -0.59 [-1.02,-0.16]). CONCLUSION: Combining rCBV and FA measurements in the peritumoral region and FA in the intratumoral region increase the accuracy of MRI examination to differentiate between HGG and SBM patients effectively. Confidence in the accuracy of our results may be influenced by major interstudy heterogeneity. Whereas the I2 for the rCBV in the intratumoral subgroup was 80%, I2 for the rCBV in the peritumoral subgroup was 39%, and I2 for the FA in the intratumoral subgroup was 69%, and I2 for the FA in the peritumoral subgroup was 74%. The predefined accurate search criteria, and precise selection and evaluation of methodological quality for included studies, strengthen this studyOur study has no funder, no conflict of interest, and followed an established PROSPERO protocol (ID: CRD42021279106). ADVANCES IN KNOWLEDGE: The combination of rCBV and FA measurements' results is promising in differentiating HGG and SBM.

Association between apolipoprotein E gene polymorphism and Alzheimer's disease in Uighur and Han populations.

AIM: Currently, there are almost 100 genes related to Alzheimer's disease (AD), and studies have indicated that apolipoprotein E (APO E) ε4 allele is a genetic risk factor of AD. However, there have been no reports of the distributions of APO E genotypes and allele frequencies in Uighur and Han AD patients. METHODS: We analyzed APO E gene polymorphism in 209 AD cases diagnosed based on National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association and 220 non-dementia controls. We used polymerase chain reaction-restriction fragment length polymorphism methods as the basis of this epidemiological survey. RESULTS: In the AD and control groups, there are no statistically significant differences in APO E genotypes and allele frequency between the Uighur and Han ethnicities (P < 0.05). In the AD group, the ε3/4 genotype (28.2%) and ε4 allele frequency (14.8%) occurred at a higher rate than in the control (13.2% and 8.0%, respectively; P < 0.05). This distinction remained true within each ethnicity; the ε3/4 genotype and ε4 allele frequency are higher in the AD groups (Uighur, 30.6% and 15.8%, respectively; Han, 25.5% and 13.8%, respectively) than in the control groups (Uighur, 14.5% and 9.4%, respectively; Han, 11.7% and 6.3%, respectively; P < 0.05). CONCLUSIONS: The distribution of APO E genotype and allele frequency does not differ between the Uighur and Han ethnicities. The APO E ε4 allele is a risk factor of AD for both populations.

Unfavorable prognostic value of human PEDF decreased in high-grade prostatic intraepithelial neoplasia: a differential proteomics approach.

BACKGROUND: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor of prostate cancer, but the frequency and timing of epigenetic changes found in prostate carcinogenesis has not been extensively documented. METHODS: Here, we performed a differential proteomic profiling study on the serum of HGPIN and prostate cancer patients. Eleven HGPIN patients were enrolled, their serum protein patterns (2D-electrophoresis and mass spectroscopy) were compared with fifteen prostate cancer patients, and the follow-up study was further performed in the HGPIN patients. RESULTS: We described eleven altered protein spots in these two groups, in which pigment epithelium-derived factor (PEDF) was found to be significantly down-regulated in prostate cancer patients, which was further confirmed by ELISA method. In addition, 18.2% (2/11) of the HGPIN revealed strong expression for PEDF, 27.3%(3/11) showed a moderate expression and 54.5% (6/11) a weak PEDF expression in immunohistochemistry study, while in prostatic cancerous cells, 100% patients (15/15) revealed a weak expression for PEDF. The ten months' follow-up study demonstrated that 2 of 6 HGPIN patients with weakly expressed PEDF were found to have subsequent prostate cancer. CONCLUSIONS: our data identified PEDF in HGPIN as a significant predictor of subsequent cancer, suggesting that PEDF implies in prostatic tumorigenesis and may be used to identify the patients with isolated HGPIN who are at high risk for cancer onset in the disease process.

Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma.

Circular RNA (circRNA) is associated with human cancers, however, few studies have reported its value in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we investigated the expression level of eight selected cancer-related circRNAs including circ-Cdr1as, circ_HIPK3 and circ-ITCH in OS cell lines, tissues and plasmas by quantitative real-time polymerase chain reaction (qRT-PCR) and found that only circ_HIPK3 could stably down-regulate in the OS cell lines, tissues and plasmas than the corresponding controlled. One-way analysis of variance was further conducted to analyze the relationship between circ_HIPK3 expression level and clinic pathological factors of OS patients. Receiver operating characteristic (ROC) curve was built to evaluate the diagnostic values of circ_HIPK3. Circ_HIPK3 expression was significantly correlated with Enneking stage (P=0.042) and lung metastasis (P=0.036). The area under the ROC curve was 0.783 and the sensitivity and specificity were 0.56 and 0.84, respectively. Kaplan-Maier analysis also showed that lower expression of circ_HIPK3 correlated with shorter overall survival time and poor prognosis of OS patients. Besides, function analysis demonstrated that circHIPK3 overexpression significantly suppressed OS cell proliferation, migration and invasion in vitro. Overall, our data suggest that circ_HIPK3 may become a novel potential biomarker for diagnosis and treatment target of OS.

Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1.

Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs generated from back-splicing, with a circular loop structure. Many circRNAs have been reported to play essential roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNA in osteosarcoma (OS) remains largely unknown. In the current study, we examined the expression level of circular RNA PVT1 (circPVT1), previously screened and identified the oncogenic role in gastric cancer, in OS and found that circPVT1 was significantly up-regulated in the OS tissues, serums and chemoresistant cell lines, correlated with poor prognosis of OS patients. Besides, ROC curve demonstrated that circPVT1 may be a better diagnostic biomarker than alkaline phosphatase (ALP) in OS with more sensitivity and specificity. In addition, functional assays revealed that circPVT1 knockdown by siRNA could weaken the resistance to doxorubicin and cisplatin of OS cells through decreasing the expression of classical drug resistance-related gene ABCB1. These findings may provide a new insight into the role of circPVT1 as a biomarker for the diagnosis and treatment target of OS.

Screening circular RNA related to chemotherapeutic resistance in osteosarcoma by RNA sequencing.

AIM: To identify circular RNAs (circRNAs) related to osteosarcoma (OS) chemoresistance. MATERIALS & METHODS: CircRNA expression profile was performed in three paired human chemoresistant and chemosensitive OS cell lines by next-generation sequencing. Quantitative real-time-PCR (qRT-PCR) was used to confirm next-generation sequencing data. Bioinformatics analysis was conducted to predict their functions. RESULTS: Eighty circRNAs were dysregulated in the chemoresistant OS cells compared with the control, after validated by qRT-PCR. Bioinformatics analysis showed that some pathways related to drug metabolism were significantly enriched. Additionally, hsa_circ_0004674 was distinctly increased in OS chemoresistant cells and tissues, related to poor prognosis. CircRNA-miRNA-mRNA pathways related to hsa_circ_0004674 were constructed by TargetScan and miRanda. CONCLUSION: CircRNAs may play a role in OS chemoresistance and hsa_circ_0004674 might be a candidate target.

LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1.

Long noncoding RNAs (LncRNAs) act as crucial regulators in various cancers including osteosarcoma (OS), yet their potential roles and molecular mechanisms in OS chemoresistance remain unclear. In the present study, we investigated the role and potential regulatory mechanism of the most down-regulated expressed lncRNA, FENDRR screened by our previous lncRNA microarray analysis between the paired doxorubicin-resistant and sensitive human osteosarcoma cell lines (MG63/DXR vs MG63). FENDRR expression was down-regulated in the doxorubicin-resistant OS cell lines and tissues and negatively correlated to the poor prognosis of OS patients. Overexpression of FENDRR suppressed doxorubicin-resistance, G2/M phase of cell cycle, and promoted cell apoptosis of osteosarcoma cells in vitro and tumor growth in vivo whereas FENDRR knockdown had the opposite effects. In addition, we found that FENDRR was mainly located in the cytoplasm and could regulate the drug resistance of osteosarcoma cells by negatively affecting posttranscriptional expression of ABCB1 and ABCC1. Together, our study demonstrated that lncRNA FENDRR may act as an inhibitory molecule of doxorubicin-resistance through down-regulating the expression of ABCB1 and ABCC1 genes in osteosarcoma cells. These findings may extend the function of FENDRR in tumor progression and provide a novel target for reversing OS chemoresistance.

Antisense lncRNA FOXF1-AS1 Promotes Migration and Invasion of Osteosarcoma Cells Through the FOXF1/MMP-2/-9 Pathway.

Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. Long non-coding RNAs (lncRNAs) have been shown to play significant role in various cancers, including OS. In a previous study, we have reported that a novel antisense lncRNA FOXF1-AS1, also known as FENDRR, could sensitize doxorubicin-resistance of OS cells through down-regulating ABCB1 and ABCC1. Here in, the critical role of FOXF1-AS1 in regulating OS progression was further investigated. Firstly, we found that FOXF1-AS1 and its antisense transcript FOXF1 expression were positively up-regulated in OS tissues and cell lines and correlated with poor prognosis of OS patients. Besides, FOXF1-AS1 as well as FOXF1 silencing significantly inhibited cell proliferation, migration, invasion of OS cells and tumor growth both in vitro and vivo through decreasing the expression of MMP2 and MMP9, whereas enhanced expression of FOXF1-AS1 had the opposite effects. In addition, mechanistically, both of FOXF1-AS1 and FOXF1 could regulate the expression of MMP2 and MMP9 at mRNA and protein levels, whereas FOXF1-AS1 could influence the FOXF1expression but FOXF1 did not have the same effect on FOXF1-AS1. Rescue assay further showed that FOXF1-AS1 overexpression efficiently reversed the knockdown of MMP2 and MMP9 expression induced by si-FOXF1. Thus, we concluded that FOXF1-AS1 may promote migration and invasion of OS cells through the FOXF1/MMP-2/-9 pathway. Taken together, these findings demonstrated the underlying mechanism of FOXF1-AS1 in the regulation of OS progression and provide a novel potential target in the OS therapy.

[Investigation of soil - transmitted nematode infections in Xiding Township, Menghai County, Yunnan Province].

OBJECTIVE: To understand the status of soil-transmitted nematode infections in Xiding Township, Menghai County, Yunnan Province, so as to provide the reference for formulating the strategy of soil-transmitted nematodosis control. METHODS: Soil-transmitted nematode eggs in feces were detected by the Kato-Katz method, and the eggs of Enterobius vermicularis were detected by the cellophane tape method in children. The soil samples were collected from vegetable, fruit and other crop fields of 15 residents randomly to detect hookworm. RESULTS: The stool samples from 1 002 residents were examined and the soil -transmitted nematode infection rate was 20.06% (201/1 002). The infection rates of hookworm, Ascaris lumbricoides and Trichuris trichura were 18.96% (190 cases), 1.70% (17 cases) and 0.90% (9 cases) respectively. The percentages of people with light infection of hookworm, A. lumbricoides and T. trichura were 97.37% (185/190), 88.24% (15/17) and 100% (9/9) respectively. No infection of E. vermicularis was found. Fifteen soil samples were tested, and no hookworm was found in the soil. CONCLUSIONS: The infection rate of soil-transmitted nematode in Xiding Township, Menghai County is high, but the infectiosity is light. The control and monitoring of soil-transmitted nematodosis should be strengthened in this area.