GRASLND regulates melanoma cell progression by targeting the miR-218-5p/STAM2 axis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation. METHODS: SiRNA transfection, wound - healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function. RESULTS: The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells. CONCLUSION: In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNA‒miRNA-mRNA functional network and a new potential therapeutic target for SKCM.

Analysis of Fluid Replacement in Two Fluidic Chambers for Oblique-Incidence Reflectivity Difference (OI-RD) Biosensor.

Optical biosensors have a significant impact on various aspects of our lives. In many applications of optical biosensors, fluidic chambers play a crucial role in facilitating controlled fluid delivery. It is essential to achieve complete liquid replacement in order to obtain accurate and reliable results. However, the configurations of fluidic chambers vary across different optical biosensors, resulting in diverse fluidic volumes and flow rates, and there are no standardized guidelines for liquid replacement. In this paper, we utilize COMSOL Multiphysics, a finite element analysis software, to investigate the optimal fluid volume required for two types of fluidic chambers in the context of the oblique-incidence reflectivity difference (OI-RD) biosensor. We found that the depth of the fluidic chamber is the most crucial factor influencing the required liquid volume, with the volume being a quadratic function of the depth. Additionally, the required fluid volume is also influenced by the positions on the substrate surface bearing samples, while the flow rate has no impact on the fluid volume.

Detection speed optimization of the OI-RD microscope for ultra-high throughput screening.

The oblique-incidence reflectivity difference (OI-RD) microscope is a label-free detection system for microarrays that has many successful applications in high throughput drug screening. The increase and optimization of the detection speed of the OI-RD microscope will enable it to be a potential ultra-high throughput screening tool. This work presents a series of optimization methods that can significantly reduce the time to scan an OI-RD image. The wait time for the lock-in amplifier was decreased by the proper selection of the time constant and development of a new electronic amplifier. In addition, the time for the software to acquire data and for translation stage movement was also minimized. As a result, the detection speed of the OI-RD microscope is 10 times faster than before, making the OI-RD microscope suitable for ultra-high throughput screening applications.

Constructing a Predictive Model of Depression in Chemotherapy Patients with Non-Hodgkin's Lymphoma to Improve Medical Staffs' Psychiatric Care.

OBJECTIVES: Depression is highly prevalent in non-Hodgkin's lymphoma (NHL) patients undergoing chemotherapy. The social stress associated with malignancy induces neurovascular pathology promoting clinical levels of depressive symptomatology. The purpose of this study was to establish an effective depressive symptomatology risk prediction model to those patients. METHODS: This study included 238 NHL patients receiving chemotherapy, 80 of whom developed depressive symptomatology. Different types of variables (sociodemographic, medical, and psychosocial) were entered in the models. Three prediction models (support vector machine-recursive feature elimination model, random forest model, and nomogram prediction model based on logistic regression analysis) were compared in order to select the one with the best predictive power. The selected model was then evaluated using calibration plots, ROC curves, and C-index. The clinical utility of the nomogram was assessed by the decision curve analysis (DCA). RESULTS: The nomogram prediction has the most efficient predictive ability when 10 predictors are included (AUC = 0.938). A nomogram prediction model was constructed based on the logistic regression analysis with the best predictive accuracy. Sex, age, medical insurance, marital status, education level, per capita monthly household income, pathological stage, SSRS, PSQI, and QLQ-C30 were included in the nomogram. The C-index was 0.944, the AUC value was 0.972, and the calibration curve also showed the good predictive ability of the nomogram. The DCA curve suggested that the nomogram had a strong clinical utility. CONCLUSIONS: We constructed a depressive symptomatology risk prediction model for NHL chemotherapy patients with good predictive power and clinical utility.

Two-dimensional stretchable blazed wavelength-tunable grating based on PDMS.

This paper reports a two-dimensional stretchable blazed wavelength-tunable grating based on polydimethylsiloxane (PDMS). In the elastic range, stretch the grating along (Y-axis) and perpendicular to (X-axis) the grating line, fix the position of the +1st-order spot to maintain the grating period, and only change the groove angle to tune the blazed wavelength. By stretching the grating up to 20% of the Y-axis, and 5.2% of the X-axis, the groove angle is reduced by 1.33°, and the blazed wavelength of the first-order diffraction shifts toward the short-wave direction by 42.3 nm. The sensitivity of a spectrometer can be enhanced by tuning the blazed wavelength of the PDMS grating to the wavelength of the spectrum peak under observation in the bands from 460.8 nm to 503.1 nm.

Silencing glioma-associated oncogene homolog 1 suppresses the migration and invasion of hepatocellular carcinoma in vitro.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-associated death worldwide. Glioma-associated oncogene homolog 1 (Gli1) is a key component and functions as a reliable marker of Hedgehog signaling pathway activation. Previous studies have demonstrated that Gli1 serves important roles in the progression of various types of cancer, including HCC. However, its effect on HCC invasion and metastasis and the underlying mechanism remain to be elucidated. Small interference RNA was employed to silence the Gli1 gene in liver cancer cells. Reverse transcription-quantitative PCR and western blot analysis were performed to evaluate the mRNA and protein expression of Gli1, respectively. A series of assays, including Cell Counting Kit-8, adhesion, wound healing and Matrigel invasion were performed to investigate cell viability, adhesive, migratory and invasive capabilities of liver cancer cells, respectively. In addition, immunofluorescence staining was performed to determine the cellular localization of focal adhesion kinase (FAK), phosphorylated (p-)FAK and p-AKT. The mRNA and protein expression of Gli1 in liver cancer cells (HepG2 and SK-Hep1) were markedly decreased in a dose-dependent manner following Gli1-knockdown. Gli1 silencing significantly inhibited the adhesion, migration and invasion of SK-Hep1 cells. Additionally, knockdown of Gli1 markedly suppressed the expression of metalloproteinase (MMP)-2 and MMP-9. Furthermore, downregulation of Gli1 blocked the FAK/AKT signaling pathway. Gli1 serves significant roles in the migration and invasion of HCC cells through activation of the FAK/AKT signaling pathway and subsequent upregulation of MMP-2 and MMP-9 expression. Thus, Gli1 may be a potential protein target for the regulation of HCC migration and invasion.

Analytical design of a high-performing +1st order diffraction convex grating imaging spectrometer.

A novel concentric spectrometer having one convex grating and one concave mirror, working at ${+}{1}$+1st order diffraction, and with a small size, high resolution, and high diffraction efficiency, is proposed. It can simultaneously achieve high resolution and compactness by increasing the grating groove density. A compact spectrometer operating at a wavelength of 740-790 nm with an excellent imaging quality is designed. Its spectral resolution reaches 0.049 nm, and its diffraction efficiency improves by 27% compared to the conventional Offner spectrometer with convex grating working at ${-}{1}$-1st order diffraction. This is suitable for small, light, and low-cost atmospheric gas monitoring satellites.

Nitrogen-Doped Carbon Nanoparticles Derived from Silkworm Excrement as On⁻Off⁻On Fluorescent Sensors to Detect Fe(III) and Biothiols.

On⁻off⁻on fluorescent sensors based on emerging carbon nanoparticles (CNPs) or carbon dots (CDs) have attracted extensive attention for their convenience and efficiency. In this study, dumped silkworm excrement was used as a novel precursor to prepare fluorescent nitrogen-doped CNPs (N-CNPs) through hydrothermal treatment. The obtained N-CNPs showed good photoluminescent properties and excellent water dispersibility. Thus, they were applied as fluorescence “on⁻off⁻on” probes for the detection of Fe(III) and biothiols. The “on⁻off” process was achieved by adding Fe(III) into N-CNP solution, which resulted in the selective fluorescence quenching, with the detection limit of 0.20 μM in the linear range of 1⁻500 μM. Following this, the introduction of biothiols could recover the fluorescence efficiently, in order to realize the “off⁻on” process. By using glutathione (GSH) as the representative, the linear range was in the range of 1⁻1000 μM, and the limit of detection was 0.13 μM. Moreover, this useful strategy was successfully applied for the determination of amounts of GSH in fetal calf serum samples.

Weight Status Is Associated with Blood Pressure, Vital Capacity, Dental Decay, and Visual Acuity among School-Age Children in Chengdu, China.

AIMS: To examine the association of weight status with the prevalence of blood pressure (BP), vital capacity, dental decay, and visual acuity among school-age children in Chengdu, China and to find the potential role of weight status to predict the common and frequently occurring diseases among school-age children. METHODS: A cross-sectional study was conducted among 12,297 children aged 6-18 years from 10 schools in the Jinniu District of Chengdu, China. Body height, weight, waist circumference (WC), and BP were measured. Vital capacity, dental decay, and visual acuity were detected. RESULTS: The overall prevalence of underweight, overweight, obesity, abdominal obesity, high BP, bad vital capacity weight index, dental decay, and low vision were 7.18, 13.47, 7.57, 18.90, 2.78, 21.93, 38.81, and 45.79%, respectively. After controlling for age, gender, and WC, it was found that overweight and obese children had a higher risk of developing high BP than normal weight children ([OR 4.20, p < 0.001] and [OR 8.76, p < 0.001], respectively), And adjusting for age, gender, and chest circumference, the risk of having bad vital capacity weight index among children with overweight and obesity was higher ([OR 2.15, p < 0.001] and [OR 5.40, p < 0.001], respectively), and the risk with underweight was lower (OR 0.35, p < 0.001). After eliminating the influential factors of gender and age, children who were underweight were 1.16 times (OR 1.16, p = 0.048) more likely to have caries than children with normal weight, but obese children were found to have a lower prevalence for dental cavities than children with normal weight (OR 0.79, p = 0.002). Underweight and obese children had a higher prevalence of low vision; the OR of the appearance of low vision was 1.21 (p = 0.016) for underweight children and 1.23 (p = 0.009) for obese children after adjusting the age and gender. CONCLUSIONS: Abnormal weight status among Chengdu urban school-age children was found to be a severe health problem, and it was strongly associated with BP, vital capacity, dental decay, and visual acuity.

Roles of ROS mediated oxidative stress and DNA damage in 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide-induced immunotoxicity of Sprague-Dawley rats.

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) has been broadly used to treat dysentery and promote animal growth in food producing animals. However, its potential toxicity could not been neglected as parts of safety assessment according to the acceptable guidelines for QCT administration. In this study, the immunotoxicity of QCT was investigated in male Sprague-Dawley (SD) rats following a 28-day oral exposure at doses of 0, 50, 800, and 2400 mg/kg/day. The food consumption, body weight gain and relative spleen weight were significantly decreased by QCT in a dose-dependent manner. Treatment of rats with QCT also notably suppressed the T-cell proliferation and natural killer (NK) cell activity, accompanied by intracellular reactive oxygen species (ROS) accumulation, antioxidant system inhibition and DNA damage enhancement. Thus, the primary finding of this study is that QCT exposure (2400 mg/kg/day) could cause immunotoxicity in SD rats due to ROS mediated oxidative stress and DNA damage.

Quinocetone-induced Nrf2/HO-1 pathway suppression aggravates hepatocyte damage of Sprague-Dawley rats.

Quinocetone (3-methyl-2-quinoxalin benzenevinylketo-1,4-dioxide, QCT) is a widely used veterinary drug in PR China that promotes feed efficiency and growth of various animals. However, its potential toxicity has been concerned recently. In the present study, we investigated QCT-induced hepatocyte changes and its related mechanism, especially the expression of Nrf2/HO-1 pathway. Oxidative stress induced by QCT in hepatocyte led to DNA damage, inflammation and apoptosis. Nevertheless, hepatocyte has a self-repair system to protect itself from oxidative stress. In the 50 mg/kg/day QCT group, the morphology and function of liver were approximately maintained on normal level, which indicated that the damaged cell might have a self-repair mechanism. Notably, nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway plays a critical role in protecting cells against reactive oxygen species (ROS) generation. However, higher doses of QCT (800 mg/kg/day and 2400 mg/kg/day) inhibited the expression of Nrf2/HO-1 pathway, which resulted in excessive ROS generation and irreversible oxidative DNA damage, inflammation and apoptosis. In conclusion, although QCT-induced oxidative stress activates the expression of Nrf2/HO-1 pathway initially, persistent QCT exposure will inhibit this expression and aggravate hepatocyte damage. Simultaneously, inflammation and apoptosis continues to progress, liver dysfunction and tissue damage will be occurred eventually.

Association of heme oxygenase-1 with the risk of polycystic ovary syndrome in non-obese women.

STUDY QUESTION: Is circulating heme oxygenase-1 (HO-1) associated with the risk of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Lower circulating HO-1 is associated with a higher risk of PCOS in non-obese women, in a dose-related manner. WHAT IS KNOWN ALREADY: PCOS is one of the most common endocrine disorders in women of reproductive age, with increasing worldwide incidence. HO-1 plays a crucial role in many physiological systems, with potent anti-inflammatory, antioxidant and antimetabolic properties. STUDY DESIGN, SIZE, DURATION: This hospital-based case-control study included 80 women with PCOS and 80 healthy control women seen at the Reproductive Center of Tongji Hospital (Wuhan, China) from November 2011 to May 2012. Cases and controls were frequency-matched on age and BMI and were enrolled into the study once written informed consent had been obtained. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum hormones, glucose, insulin and lipid concentrations were measured using an automated platform. Correlation coefficients and multiple linear regression models were calculated in the combined group (both cases and controls) using serum HO-1 concentration as the independent variable and age and BMI as covariate variables to explore the association between HO-1 and the pathophysiology of PCOS. To examine the independent association of serum HO-1 levels with the likelihood of PCOS, multivariate logistic analysis was used. The strength of the association was tested further by receiver-operating characteristic (ROC) curve models, with or without the addition of HO-1. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with controls, women with PCOS were found to have significantly increased insulin resistance (IR), oxidative stress (OS) and inflammation levels, creating a vicious circle of effects in the pathophysiology of PCOS. However, serum HO-1 was negatively associated with this vicious circle. Women with the highest tertile of HO-1 (≥5.29 ng/ml) had an odds ratio (OR) of PCOS of 0.02 (95% CI 0.0034-0.07) compared with women with the lowest quartile (<3.14 ng/ml) (P < 0.01). This trend remained after adjustment for potential confounders in the multivariable model (all P < 0.01). ROC analysis based on an existing prognostic model yielded significantly discriminative values for PCOS, with or without the addition of HO-1 (areas under the curves were 0.86 (95% CI 0.81-0.92) versus 0.95 (95% CI 0.92-0.98); P for difference = 0.0005). LIMITATIONS, REASONS FOR CAUTION: It is difficult to establish a time-integrated measure of circulating HO-1 during the progression of PCOS and these findings should be confirmed in large-scale studies involving different ethnic groups. Moreover, the study lacks measurements of glycated hemoglobin (HbA1c) to provide an index of blood glucose concentrations over time. WIDER IMPLICATIONS OF THE FINDINGS: Circulating HO-1 that provides protection against IR, OS and chronic inflammation is markedly reduced in non-obese women with PCOS. Low serum HO-1 is suggested as an independent risk factor for PCOS; thus, circulating HO-1 levels may be a novel biomarker for PCOS in young, non-obese women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Natural Science Foundation of China (81202210) and the National Science and Technology Support Program of China (2012BAI02B02). None of the authors has any conflict of interest to declare.

Serum Heat Shock Protein 70 Concentration in Relation to Polycystic Ovary Syndrome in a Non-Obese Chinese Population.

BACKGROUND: Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 6-15% of women of reproductive age. However, the underlying etiology is still poorly understood. In this study, we attempted to examine the association between circulating heat shock protein 70 (Hsp70) concentrations and PCOS in a non-obese Chinese population. METHODS AND RESULTS: Human peripheral blood from 52 patients with PCOS and 57 healthy controls, matched for age and BMI, were analyzed. Women with PCOS were found to have significantly higher fasting insulin (FI) levels, as well as Insulin resistance index (HOMA-IR) (P < 0.05). Identically, markers of oxidative stress (malondialdehyde (MDA), 8-Hydroxy-desoxyguanosine (8-OHdG), Nitric oxide (NO)) and inflammation (tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)) were markedly increased when compared to controls (P < 0.05). Elevated serum Hsp70 was positively correlated with IR, oxidative stress and inflammation in PCOS, even after adjustment for age, BMI and gynecologic inflammation (GI). The receiver-operating characteristic curve (ROC) analysis yielded notably different discriminative value for PCOS, with or without an addition of Hsp70 (areas under the curves were 0.884 (95% CI 0.822-0.946) vs. 0.822 (95% CI 0.744-0.900); P for difference = 0.015). CONCLUSIONS AND SIGNIFICANCE: Increased serum Hsp70 levels are associated with the combination of IR, oxidative stress and low-grade chronic inflammation in PCOS individuals, which provides supportive evidence that Hsp70 plays a key role in the pathogenesis of PCOS. More consequent studies were warranted to confirm the clinical utility of circulating Hsp70, especially in diagnosis and prognosis of PCOS and its long-term health cost.

Nrf2/ARE is the potential pathway to protect Sprague-Dawley rats against oxidative stress induced by quinocetone.

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) is a newly used veterinary drug which has been proven to promote feed efficiency and growth of animals; however, its potential toxicity can't be ignored. Therefore, the present study was aimed to investigate the nephrotoxicity of QCT and the oxidative stress induced by it. Sprague-Dawley rats (SD rats) were randomly divided into four groups with doses of 2400, 800, 50 and 0mg/kg/day with administration of QCT for 4 weeks. Results proved that QCT could induce nephrotoxicity and this phenomenon had dose dependent manner. Simultaneously, this phenomenon was accompanied by intracellular reactive oxygen species (ROS) accumulation, enhanced lipid peroxidation and inhibited antioxidant system, i.e. glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GSH). Additionally, the higher expression of Nrf2 in QCT treated groups illustrated that QCT-induced oxidative stress would be partly mitigated by the induction of phase II detoxifying enzymes via increasing Nrf2 expression.

Evaluation of oral subchronic toxicity of Pu-erh green tea (camellia sinensis var. assamica) extract in Sprague Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pu-erh green tea, originally produced in the Yunnan province of P.R. China for about 1700 years, is believed to be beneficial to health in Asian countries. The potential toxicity of Pu-erh green tea when administered at high doses via concentrated extract, however, has not been completely investigated. THE AIM OF THE STUDY: The present study was aimed to evaluate the potential toxicity of Pu-erh green tea extract (PGTE) of sub-chronic administration to Sprague Dawley (SD) rats. MATERIALS AND METHODS: Growing SD rats were administrated orally by gavage with PGTE at doses of 0, 1250, 2500, and 5000 mg/kg/day for 91 consecutive days. Clinical observations, including survival, hematology, serum biochemistry, urinalysis and histopathological examination were measured to monitor treatment-related adverse effects in rats. RESULTS: The results showed that oral administration of high dose of PGTE led to body weight gain suppression, liver and calcium deposition dysfunctions. CONCLUSIONS: In conclusion, the no-observed-adverse-effect level for Pu-erh green tea extract derived from the results of the present study was 2500 mg/kg/day for both genders.

Pu-erh black tea extract supplementation attenuates the oxidative DNA damage and oxidative stress in Sprague-Dawley rats with renal dysfunction induced by subchronic 3-methyl-2-quinoxalin benzenevinylketo-1,4-dioxide exposure.

3-Methyl-2-quinoxalin benzenevinylketo-1,4-dioxide (Quinocetone, QCT), has been used to treat dysentery and promote growth in animal feeding. However, available data show that QCT has potential nephrotoxicity. The present study was designed to investigate the protective effects of Pu-erh black tea extract (PBTE) which is a traditional remedy in China with antioxidant properties against oxidative DNA damage and oxidative stress in a rat model of QCT-induced renal dysfunction. Increased serum creatinine, blood urea nitrogen, pathological lesions, urinary 8-hydroxy 2-deoxyguanosine (8-OHdG) and renal DNA damage were observed in the QCT-fed rats. These were accompanied by intracellular reactive oxygen species accumulation, enhanced lipid peroxidation, and inhibited antioxidant system, i.e., glutathione glutathione S-transferase, glutathione peroxidase and glutathione reductase. Oral administration of PBTE effectively suppressed QCT-induced renal dysfunction, as evidenced by reduced serum creatinine, urinary 8-OHdG and DNA damage in isolated renal cells, amelioration of oxidative stress and modulation of antioxidative system. In conclusion, PBTE administration ameliorated QCT-induced nephrotoxicity by maintaining DNA's double-helix architecture and mitigating oxidative stress.