MicroRNA-802 promotes the progression of osteosarcoma through targeting p27 and activating PI3K/AKT pathway.

PURPOSE: Increasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS. METHODS: RT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial-mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802. RESULTS: MiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS. CONCLUSION: MiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.

Improving electric thermal stability of polypropylene by chemically linking small amount of hindered phenol groups.

Thermal stability of polypropylene (PP) over a broad temperature is critical for many applications. Hindered phenol (HP) groups have been utilized in PP for thermal-oxidative protection. This paper studies thermal stability of the electret property of PP linked with 0.2 mol% HP. It is observed that small amount of chemically linked HP groups improves electret thermal stability as reflected by the higher peak temperature of the thermally stimulated discharge curve and about 65% increase in the trap level. In addition, the HP groups in PP generate "rigid backbones" which maintain the PP film shapes to temperatures near the melting (~ 150 °C), compared with pristine PP at 70 °C. SUPPLEMENTARY INFORMATION: The online version of this article (10.1557/s43580-021-00016-1) contains supplementary material, which is available to authorized users.

Analysis of altered miRNA profiling in the colon of a mouse model with ß-lactoglobulin allergy.

OBJECTIVES: The differences in the expression profiles of colonic miRNAs between ß-lactoglobulin (ß-Lg) allergic mice and normal mice were analyzed to investigate the important role of the miRNA regulation mechanism in the pathogenesis of cow's milk allergy. METHODS: The present study performed Illumina sequencing to characterize the miRNA profile changes in mouse colon responding to ß-Lg challenge. Target genes were predicted by TargetScan 50 and miRanda 3.3a algorithms and assessed by GO and KEGG analysis. The expression levels of selected miRNAs and cytokine production were verified by cell transfection and quantitative RT-PCR. RESULTS: A total of 15 miRNAs were diversely expressed between the colon of the normal and ß-Lg-sensitized mice (P < 0.05, fold change of >1.50 or <0.67), including six up-regulated miRNAs and nine down-regulated miRNAs, among which seven miRNAs were validated using qRT-PCR. GO enrichment and KEGG pathway analyses further revealed that biological process, protein binding, cytoplasm and the pathways of cancer were significantly enriched, which were closely connected to the allergic inflammation development. Additionally, six key functional interaction pairs in ß-Lg allergy were identified in miRNA prediction algorithms and verified using qRT-PCR. CONCLUSIONS: We can conclude that our results suggested that the miRNAs regulation network participated in the pathogenesis of cow's milk allergy.

Room Temperature Magnetoelectric Sensor Arrays For Application of Detecting Iron Profiles in Organs.

Noninvasive measurement of liver iron concentration (LIC) is clinically important. Yet, at the present time, it can only be achieved with SQUID technology. However, SQUID based BLS suffers high costs and cumbersome cryogenic requirements that prevent SQUID BLS from being adopted by clinical applications. Recently, we demonstrated that a single channel ME sensor with piezo-single crystals could detect LIC from only 3cc of mouse liver tissue without any magnetic field shielding. The results demonstrated not only the sensitivity of ME sensor system for LIC but also the feasibility for mapping LIC profiles spatially. This investigation further developed ME sensor arrays, exploiting the compact size and room temperature operation. A Dual-Channel 1-D ME sensor array along the vertical, Z-direction, was developed and shown to be sensitive to the skin-liver distance change which can be utilized to calibrate and eliminate the inter-subject variability of the LIC measurement due to skin-liver distance. With phantom having spatially dependent iron concentrations, the 1-D ME sensor array was capable of mapping the one-dimensional profile of the iron concentration in the horizontal X- and Y-directions. The results of the prototype sensor devices show the feasibility of an array ME-sensors for imaging iron profile.

[Impact of diagnostic ureteroscopy and biopsy on radical nephroureterectomy of upper tract urothelial carcinoma].

OBJECTIVE: To investigate the impact of preoperative diagnostic ureteroscopy and biopsy (UB) on radical nephroureterectomy (RNU) and the prognosis of upper tract urothelial carcinoma (UTUC). METHODS: The clinical data of UTUC patients receiving RNU between Jan. 2007 and Dec. 2016 were retrospectively collected. The median follow up time was 40 months. The operation time and blood loss of RNU were compared between UB group and non-UB group. Subgroup analyses were conducted according to the time interval between UB and RNU, and surgery methods of lower ureter. The linear regression model was used to adjust for other common factors that impacted operation time. RESULTS: A total of 163 UTUC patients were included in the final analysis. For the lower ureter, open ureterectomies were performed in 91 patients (55.9%), while retroperitoneal laparoscopic ureterectomies were performed in 72 patients (44.1%). A total of 110 (67.5%) patients received preoperative UB. Compared with non-UB group, the average operation time of UB group was significantly longer [(252.5±79.8) min vs. (221.3±79.8) min, P=0.019], but no difference of blood loss was found (median, 50 mL vs. 50 mL, P=0.143). In subgroup analysis, the average operation time of RNU was significantly prolonged when RNU was performed after 1 week of UB (P=0.023). Meanwhile, the median blood loss of RNU increased significantly when it was done after 2 weeks of UB compared with non-UB group (100 mL vs. 50 mL, P=0.012). UB was also significantly prolonged the operation time of RNU in retroperitoneal laparoscopic ureterectomy group (P=0.012). In multivariable analysis, UB (P=0.049), ≥pT3 (P=0.039), pN+ (P=0.018) and ureterectomy method (P=0.005) were independent risk factors of prolonged operation time. The 3-year cancer specific survival (CSS) rate was 87.2% in our cohort. UB had no significant impact on cancer specific survival (P=0.435). CONCLUSION: UB was an independent risk factor of prolonged RNU time, but did not significantly influence cancer specific survival of upper tract urothelial carcinoma patients.

[Perioperative management of endoscopic ear surgery].

With the rapid development of modern equipment and widespread familiarity with the relative knowledge, endoscopic ear surgery has attracted many oto-surgeons and is becoming more popular in primary hospitals in China. Standardized management of perioperative period in this field can help surgeons shorten the learning curve and avoid potential complications in endoscopic ear surgery. In this article, the management technique was introduced in detail, covering five main aspects including handling of related in-struments, preoperative examination and preparation, informed consent, preparation for patients and operation room setup. Extra focus was placed on the manipulation and resolution of possible difficulties during the procedure.

A Novel Magnetoelectric Biomagnetic Susceptometer on Iron Level Detection with Mice Tissue in Vitro.

Iron plays a vital role in human body. Liver Iron Concentration (LIC) is directly correlated to total body iron and can be an important indicator to a variety of pathologies. Non-invasive methods to quantitatively assess tissue iron with low cost and high sensitivity have drawn vast interests and investments. Among various methods, the magnetoelectric (ME) sensor based biomagnetic liver susceptometer (BLS) is of great promise because it operates at room temperature but with the same principle as that of the well-developed SQUID (Superconducting Quantum Interference Device). Here, we report a magnetoelectric (ME) sensor based BLS system exploiting the recently developed PIN-PMN-PT piezoelectric single crystal. The newly developed ME BLS, which employs the horizontal scanning mechanism with a water bath interface to automatically eliminate the diamagnetic background of the tissues and irregular shape of torso, exhibits an overall sensitivity advancement (300X) to the sensor system previously reported. A linear correlation (R2 = 0.97) found between the system measurements and the biopsy data demonstrates the validity of the system. The ability to detect signals from only 3cc of mouse liver tissue samples suggests a high spatial resolution which could be used for finer scanning and enable magnetic distribution image and profiling.

Decreased expression of miR-490-3p in osteosarcoma and its clinical significance.

OBJECTIVE: Increasing evidence has revealed that miRNAs play a key role in the development and progression of tumor and are being explored as a prognostic biomarker. The aim of this study was to investigate the clinical significance of miR-490-3p expression in osteosarcoma. PATIENTS AND METHODS: Quantitative real-time PCR (qRT-PCR) was used to evaluate miR-490-3p level in osteosarcoma tissues. We also analyzed the correlations between the expression level of miR-490-3p and the clinical characteristics in cases of osteosarcoma. Also, Kaplan-Meier curve and the log-rank test were conducted to detect the prognostic value of miR-490-3p. Finally, univariable and multivariable Cox regression analyses were used to evaluate independent prognostic factors. RESULTS: MiR-490-3p expression level was significantly downregulated in osteosarcoma tissues in comparison with noncancerous bone tissues. Moreover, low miR-490-3p expression was significantly associated with distant metastasis, advanced clinical stage and poor overall survival and relapse-free survival. Univariate and multivariate analysis results indicated that miR-490-3p was an independent prognostic factor in osteosarcoma. CONCLUSIONS: Our results showed that miR-490-3p plays critical roles in osteosarcoma progression and serves as a novel prognostic indicator and a potential therapeutic target for osteosarcoma.

A Room Temperature Ultrasensitive Magnetoelectric Susceptometer for Quantitative Tissue Iron Detection.

Iron is a trace mineral that plays a vital role in the human body. However, absorbing and accumulating excessive iron in body organs (iron overload) can damage or even destroy an organ. Even after many decades of research, progress on the development of noninvasive and low-cost tissue iron detection methods is very limited. Here we report a recent advance in a room-temperature ultrasensitive biomagnetic susceptometer for quantitative tissue iron detection. The biomagnetic susceptometer exploits recent advances in the magnetoelectric (ME) composite sensors that exhibit an ultrahigh AC magnetic sensitivity under the presence of a strong DC magnetic field. The first order gradiometer based on piezoelectric and magnetostrictive laminate (ME composite) structure shows an equivalent magnetic noise of 0.99 nT/rt Hz at 1 Hz in the presence of a DC magnetic field of 0.1 Tesla and a great common mode noise rejection ability. A prototype magnetoelectric liver susceptometry has been demonstrated with liver phantoms. The results indicate its output signals to be linearly responsive to iron concentrations from normal iron dose (0.05 mg Fe/g liver phantom) to 5 mg Fe/g liver phantom iron overload (100X overdose). The results here open up many innovative possibilities for compact-size, portable, cost-affordable, and room-temperature operated medical systems for quantitative determinations of tissue iron.

An Ultrasensitive Magnetoelectric Sensor System For the Quantitative Detection of Liver Iron.

Ultrasensitive magnetoelectric (ME) sensors have been developed using magnetostrictive/piezoelectric laminate heterostructures. This paper discusses a highly interdisciplinary design of a room temperature biomagnetic liver susceptometry system (BLS) based on the ME sensors. The ME-sensor based BLS maintains the ultrahigh sensitivity to detect the weak AC biomagnetic signals and introduces a low equivalent magnetic noise. The results reveal a "turning point" and successfully indicate the output signals to be linearly responsive to iron concentrations from normal iron level (0.05 mgFe/gliver phantom) to 5 mgFe/gliver phantom iron overload level (100X overdose). Further, the introduction of the water-bag technique shows the promise on the automatic deduction of the background (tissue) signal, enabling an even higher sensitivity and better signal-to-noise (SNR). With these improvements, it becomes feasible to get improved characterization flexibility and the field distribution mapping potential via signal processing from the correlations of multiple sensors in the system. Considering the wide presence of biomagnetic signals in human organs, the potential impact of such biomagnetic devices on medicine and health care could be enormous and far-reaching.

DNA methyltransferase 3B -149C/T polymorphism and the risk of laryngeal squamous cell carcinoma: a case-control study.

A variety of molecular epidemiological studies have been conducted to examine the association between the DNMT3B -149C/T polymorphism and cancer susceptibility; however, there has been no study investigating the association between the DNMT3B -149C/T polymorphism and the risk of laryngeal squamous cell carcinoma (LSCC) until now. To determine the role of the DNMT3B -149C/T polymorphism in LSCC, we genotyped 113 patients with LSCC and 110 controls from a Chinese population using polymerase chain reaction-restriction fragment length polymorphism analysis. The chi-square test was used to examine differences in the distributions of genotypes studied between patients and controls. The association between the DNMT3B -149C/T polymorphism and the risk of LSCC was estimated using ORs and their 95%CIs. Genotypic frequencies in the patients with LSCC were not similar to those of the controls, with the differences being statistically significant (P = 0.001). When the DNMT3B -149 CC genotype was used as the reference group, the CT genotype was not associated with LSCC risk (adjusted OR, 2.12; 95%CI = 0.89-5.19; P = 0.07), but the TT genotype was associated with significantly increased risk for LSCC (adjusted OR = 3.27; 95%CI = 1.79-10.66; P = 0.009). Under the recessive model of inheritance, the TT genotype was associated with significantly increased risk for LSCC (adjusted OR = 1.98; 95%CI = 1.12-5.95; P = 0.012), compared with other genotypes. These results suggested that the DNMT3B -149C/T polymorphism is associated with a genetic susceptibility for developing LSCC in a Chinese population.

Cancer testis antigen OY-TES-1: analysis of protein expression in ovarian cancer with tissue microarrays.

UNLABELLED: Revised manuscript accepted for publication March 5, Objectives: The purpose of this study was to determine the potential of cancer testis antigen OY-TES-1 as a vaccine for ovarian cancer (OC). MATERIALS AND METHODS: A tissue microarray (TMA) containing 107 samples from OC tissues and 48 samples from OC adjacent tissues was analyzed by immunohistochemistry with the OY-TES-1 polyclonal antibody. The correlation between OY-TES-1 and clinic pathological traits of OC was statistically analyzed. RESULTS: The expression of OY-TES-1 protein was found in 81% (87/107) of OC tissues and 56% (27/48) of OC adjacent tissues. The immunostaining intensity of OY-TES-1 in OC tissues was significantly higher than that in OC adjacent tissues tested (p = 0.040). OC adjacent tissues only demonstrated lower immunostaining intensity, whereas some of OC tissues presented higher immunostaining intensity and majority showed the heterogeneity of protein distribution. There was no statistically significant correlation found between OY-TES-1 expression and any other clinicopathological traits such as age, FIGO stage, pathological grade, and histological type. CONCLUSIONS: OY-TES-1 was expressed in OC tissues with a high proportion, and some of OC tissues presented OY-TES-1 expression in high level vs OC adjacent tissues. OY-TES-1 could be an attractive target for immunotherapy for OC in the future.

Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli.

PURPOSE: In order to clarify the cellular processing and repair mechanisms for radiation-induced clustered DNA damage, we examined the correlation between the levels of DNA glycosylases and the sensitivity to ionizing radiation in Escherichia coli. MATERIALS AND METHODS: The lethal effects of gamma-rays, X-rays, alpha-particles and H2O2 were determined in E. coli with different levels of DNA glycosylases. The formation of double-strand breaks by post-irradiation treatment with DNA glycosylase was assayed with gamma-irradiated plasmid DNA in vitro. RESULTS: An E. coli mutM nth nei triple mutant was less sensitive to the lethal effect of sparsely ionizing radiation (gamma-rays and X-rays) than the wild-type strain. Overproduction of MutM (8-oxoguanine-DNA glycosylase), Nth (endonuclease III) and Nei (endonulease VIII) increased the sensitivity to gamma-rays, whereas it did not affect the sensitivity to alpha-particles. Increased sensitivity to gamma-rays also occurred in E. coli overproducing human 8-oxoguanine-DNA glycosylase (hOgg1). Treatment of gamma-irradiated plasmid DNA with purified MutM converted the covalently closed circular to the linear form of the DNA. On the other hand, overproduction of MutM conferred resistance to H2O2 on the E. coli mutM nth nei mutant. CONCLUSIONS: The levels of DNA glycosylases affect the sensitivity of E. coli to gamma-rays and X-rays. Excessive excision by DNA glycosylases converts nearly opposite base damage in clustered DNA damage to double-strand breaks, which are potentially lethal.

Identification of proteins of Escherichia coli and Saccharomyces cerevisiae that specifically bind to C/C mismatches in DNA.

The pathways leading to G:C-->C:G transversions and their repair mechanisms remain uncertain. C/C and G/G mismatches arising during DNA replication are a potential source of G:C-->C:G transversions. The Escherichia coli mutHLS mismatch repair pathway efficiently corrects G/G mismatches, whereas C/C mismatches are a poor substrate. Escherichia coli must have a more specific repair pathway to correct C/C mismatches. In this study, we performed gel-shift assays to identify C/C mismatch-binding proteins in cell extracts of E. COLI: By testing heteroduplex DNA (34mers) containing C/C mismatches, two specific band shifts were generated in the gels. The band shifts were due to mismatch-specific binding of proteins present in the extracts. Cell extracts of a mutant strain defective in MutM protein did not produce a low-mobility complex. Purified MutM protein bound efficiently to the C/C mismatch-containing heteroduplex to produce the low-mobility complex. The second protein, which produced a high-mobility complex with the C/C mismatches, was purified to homogeneity, and the amino acid sequence revealed that this protein was the FabA protein of E.COLI: The high-mobility complex was not formed in cell extracts of a fabA mutant. From these results it is possible that MutM and FabA proteins are components of repair pathways for C/C mismatches in E.COLI: Furthermore, we found that Saccharomyces cerevisiae OGG1 protein, a functional homolog of E.COLI: MutM protein, could specifically bind to the C/C mismatches in DNA.

Morphological analysis of lymph vessels and capillaries in gastric carcinoma.

AIM: To investigate the morphology of lymph vessel capillaries in both human gastric carcinomas and their peritumoral tissues, as well as the relation of this morphology to lymphatic metastasis. METHODS: The morphology and fine distribution of both lymph vessels and capillaries in and around the primary foci of gastric carcinoma were studied using the 5'Nase Alpase double staining method. The total amount of opened vessels and the opening rate of lymph vessels and capillaries were counted using a light microscope (100 × magnification), and the maximal luminal area, perimeter and diameter were measured using an image analysis technique. RESULTS: Lymph vessels and capillaries displayed strong 5'Nase-positive staining (brown and dark brown), while blood vessels and capillaries revealed significant Alpase activity (blue). There were many lymph vessels, capillaries and solid strip-like tissues found in the gastric carcinoma samples analyzed. The total amount of lymphatics in the metastatic group (gastric carcinoma vs peritumoral tissue) and non-metastatic group was 26.9 ± 14.2 vs 10.4 ± 4.0, 11.4 ± 3.4 and 9.7 ± 3.2, P < 0.01, respectively. Their opening rates were 21.2 vs 47.5 and 40.4 vs 46.0, P < 0.01, respectively. Their maximal luminal areas were 1502.98 ± 1236.91 vs 5526.80 ± 4853.42; 1918.14 ± 2299.24 vs 3836.16 ± 3549.16; 5526.80 ± 4853.42 vs 3836.16 ± 3549.16, P < 0.05, their perimeters were 220.33 ± 130.25 vs 441.43 ± 276.51; 241.79 ± 171.13 vs 333.80 ± 199.66; 441.43 ± 276.51 vs 333.80 ± 199.60, P < 0.05, and their diameters were 28.80 ± 14.98 vs 59.39 ± 28.53; 25.37 ± 15.79 vs 46.22 ± 20.85; 59.39 ± 28.53 vs 46.22 ± 20.85, P < 0.05, respectively. In summary, the lymphatics found in gastric carcinoma samples from the metastatic group were significantly lower than those of the other groups. CONCLUSION: There are newly formed lymph capillaries found in gastric carcinoma. Dilation of lymph capillaries may be related to edema found in peritumoral connective tissues. The observed lymph node metastases from gastric carcinoma occur through mature lymph capillaries that invade in and around primary gastric carcinoma foci.

Enzymatic release of 5-formyluracil by mammalian liver extracts from DNA irradiated with ionizing radiation.

To identify a repair enzyme for 5-formyluracil (5-FU) caused by ionizing radiation in DNA, we used a radiolabelled product-release assay for this thymine-damaged substrate. Double-stranded poly(dA-dT)-poly(dA-dT) was radiolabelled by nick translation with [2-14C]-thymidine triphosphate. The DNA was irradiated with X-rays and incubated with cell extract from mouse liver. Radiolabelled products released from the irradiated DNA into an ethanol-soluble fraction were analysed by reversed-phase hplc. Released 5-FU was detected as a free base during reaction with the cell extract. 5-Formyl-2'-deoxyuridine was not detected in the ethanol supernatant. Boiling the extract at 97 degrees C for 15 min completely abolished its ability to release 5-FU. Similar enzymatic activity was observed with rat liver extract. These results demonstrated that mammalian cells have enzymatic activity to release 5-FU from DNA.

[Clinical study of subclinical hepatic cancer--analysis of 187 patients].

187 patients with subclinical hepatic cancer (SHC), collected by mass screening or follow-up of the hepatic diseases in our hospital from Dec. 1972 to Dec. 1984, are reported. The age ranged from 18 to 76 years with a median of 47. The sex ratio of male and female was 1.97:1. 143 (76.5%) patients had a positive pathology. The exploration rate was 60.4% and resection rate was 77.9%. Of them, there were 72 (81.8%) small liver cancers with lesions equal to or less than 5 cm in diameter. For patients with resection, the 1, 3 and 5 year survival rates were 77.3%, 39.3% and 34.6%, markedly higher than those treated by other means. B-ultrasonography gave a significantly higher positive rate (96.4%) in the localization of SHC, compared with nuclide imaging (17.6%). Basing on analysis of 187 patients with SHC, close follow-up of the subjects with low level persistent positive alpha-fetoprotein without active liver disease plays an important role in the early detection of SHC.

[Fine needle aspiration cytology in the diagnosis of primary liver cancer].

From Dec. 1979 to Dec. 1984, 171 patients suspicious of primary liver cancer (PLC) were examined by fine needle aspiration cytology (FNAC). In this series, 148 patients were finally diagnosed as PLC. By FNAC, 133 of 148 patients showed positive cytology and 4 suspiciously positive cytology. The overall diagnostic accuracy was 92.6% There was no false positive. Neither spreading or bleeding were observed. The results show that FNAC examination, being simple, rapid and safe, could serve as a reliable way of diagnosing the suspected PLC.