• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1057-1060
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• 2013

Recent investigations have confirmed up-regulation of serum miR-21 and its diagnostic and prognostic value in several human malignancies. In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1563-1567
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• 2012

To investigate the relationship between serum miRNA-21 (miR-21) expression in esophageal squamous cell carcinomas (ESCCs) and its clinicopathologic features, a 1:1 matched case-control study including 21 patients with ESCC and 21 age- and gender-matched healthy controls was carried out. Serum specimens were taken from all subjects. Total RNA was extracted and the stem-loop real time polymerase chain reaction was used to measure serum miR-21 in both groups. Clinical parameters were assessed to determine associations with serum miR-21 concentrations. Serum miR-21 expression in ESCC samples was significantly higher than in paired cancer-free samples (P<0.05). Metastasis was associated with mir-21 expression in serum (P<0.05), ESCC patients with metastasis having 8.4-fold higher serum miR-21 concentrations than healthy controls. There were no statistically significant associations between miR-21 expression and clinicopathologic parameters, such as gender (P>0.05), age (P>0.05), tumor location (P>0.05), cell differentiation (P>0.05), TNM staging (P>0.05), whether chemo/radiotherapy had been administered (P>0.05), or whether surgery had been performed (P>0.05). These findings suggest that the detection of microRNA-21 in serum might serve as a new tumor biomarker in diagnosis and assessment of prognosis of ESCCs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7529-7536
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• 2013

Background and Aims: MicroRNA-21 (miR-21) is reported to be overexpressed and to contribute to proliferation, apoptosis and gemcitabine resistance in pancreatic ductal adenocarcinomas (PDACs). The aims of this study were to explore regulation of miR-21 expression by epigenetic change and its impact on chemoresistance and malignant properties of of pancreatic cancer. Materials and methods: We retrospectively collected 41 cases of advanced pancreatic cancer patients who were sensitive or resistant to gemcitabine and assessed levels of serum circulating miR-21 for correlation with cytotoxic activity. Histone acetylation in the miR-21 promoter was also studied in gemcitabine-sensitive and gemcitabine-resistant PDAC cells. Gemcitabine-resistant HPAC and PANC-1 cells were transfected with pre-miR-21 precursors (pre-miR-21) and antisense oligonucleotides (anti-miR-21), and were treated with TSA. Finally, invasion and metastasis assays were performed and alteration in mir-21, PTEN, AKT and pAKT level was evaluated in these cells. Results: Serum miR-21 levels were increased in gemcitabine-resistant PDAC patients compared with gemcitabine-sensitive subjects. The miR-21 levels were increased in 6 PDAC cells treated with gemcitabine significantly, associated with 50% inhibitory concentrations ($IC_{50}s$). Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAKT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAKT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAKT expressions induced by gemcitabine. Conclusions: MiR-21 upregulation induced by histone acetylation in the promoter zone is associated with chemoresistance to gemcitabine and enhanced malignant potential in pancreatic cancer cells.

• Journal of Nutrition and Health
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• v.55 no.1
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• pp.36-46
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• 2022

Purpose: Quercetin is a polyphenolic flavonoid abundant in many fruits and vegetables. It has potential health-beneficial properties, such as antioxidant, anti-obesity, anti-cancer, anti-diabetic and anti-inflammatory effects. The purpose of this study was to investigate whether the lipid metabolism improvement effect of quercetin affected the regulation of AMP-activated protein kinase (AMPK) activity and microRNA (miR)-21 expression in the liver of mice fed a high-cholesterol diet. Methods: Male C57BL/6J mice were fed with normal diet, quercetin-free diet and diets containing 0.05% or 0.1% quercetin for six weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Serum and liver triglyceride (TG), and total cholesterol (TC) concentrations were analyzed using a commercial enzymatic colorimetric kit. AMPK activity was quantified using an AMPK kinase assay kit. The levels of miR-21 and genes involved in lipid metabolism were measured by real-time quantitative polymerase chain reaction. Results: Supplementation of quercetin reduced serum and hepatic TG and TC levels without changing body weight and food intake. Dietary quercetin significantly inhibited the mRNA levels of hepatic sterol-regulatory element binding protein-1c, acetyl-CoA carboxylase 1 and fatty acid synthesis, which are involved in hepatic lipogenesis. Dietary quercetin enhanced AMPK activity and suppressed miR-21 expression, promoting hepatic lipid accumulation. Conclusion: These results suggest that the lipid-lowering effect of quercetin on the serum and liver of mice may be partially mediated by the regulation of lipogenic gene expression, AMPK activity and miR-21 expression in the liver of mice fed a high-cholesterol diet.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7551-7554
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• 2013

Tumor-associated microRNAs have been detected in serum or plasma, but whether plasma microRNA-21 (miR-21) could be a potential circulating biomarker for gastric cancer (GC) prognosis in Chinese is still uncertain. Real-time quantitative reverse transcription PCR (qRT-PCR) was employed in this study to compare the relative expression of miR-21 between pre-operative and post-operative paired plasmas from 42 patients with primary GCs. The results showed that the expression levels of miR-21 in the post-operative plasmas were significantly reduced by an average of 18.2 times in all patients when compared to the pre-operative plasmas, and by 22.1 times in the subgroup of patients without family history, while only 1.76 times in the subgroup of patients with a family history. With respect of clinicopathological characteristics, the plasma miR-21 expression was highly associated with differentiation degree and lymph node metastasis rate. The results suggested plasma miR-21 could be a novel potential biomarker for GC prognosis and evaluation of surgery outcomes, especially in patients without a family history.

• Herbal Formula Science
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• v.17 no.2
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• pp.133-142
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• 2009

Objective : Recently, obesity has increased at an alarming rate and is now a worldwide health problem. Natural dietary supplement, $CharmSlim^{(R)}$(C), is mixed pills, which consists of beans, black sesames, kelps, onions, adlay seeds, anchovies, pyogo mushrooms, green tea. Our study was performed to determine the weight-loss effects of natural dietary supplement, based on natural ingredients, in mice fed high-fat diet with an abundance of carbohydrates. Methods : Four groups of male ICR mice were fed different diets during 6 weeks: normal diet(NOR), high-fat (15%, w/w) diet(HF), high-fat supplemented with natural dietary supplement powdered 5%(C5) and 10%(C10) groups. We measured the changes of food intake, body weight and adipose tissues weights. Also we examined levels of lipid profiles in serum. Results : Body weight, liver weight and food efficiency ratio were significantly higher in the HF group than in NOR group. After 6 weeks of treatment, body weight, liver weight and adipose tissues weights (epididymal, perinephric, visceral and BAT) were significantly decreased in the C10 group when compared to the control HF group. The C10 group had markedly lower serum levels of total cholesterol and triglyceride when compared with HF group. Conclusion : These results demonstrate that this dietary supplement can suppress the increased lipid profiles, body weight and fat gains, thus could be considered as an effective adjunct in the treatment of obesity.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.363-370
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• 2018

Purpose: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. Methods: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. Results: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. Conclusion: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.

• Journal of Veterinary Science
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• v.21 no.6
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• pp.81.1-81.10
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• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.153-158
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• 2011

Objective: The aim of this study was to investigate whether anti-M$\ddot{u}$llerian hormone (AMH) levels could be predict ovarian poor/hyper response and IVF cycle outcome. Methods: Between May 2010 and January 2011, serum AMH levels were evaluated with retrospective analysis. Three hundred seventy infertile women undergoing 461 IVF cycles between the ages of 20 and 42 were studied. We defined the poor response as the number of oocytes retrieved was equal or less than 3, and the hyper response as more than 25 oocytes retrieved. Serum AMH was measured by commercial enzymelinked immunoassay. Results: The number of oocytes retrieved was more correlated with the serum AMH level (r=0.781, $p$ <0.01) than serum FSH (r=-0.412, $p$ <0.01). The cut-off value of serum AMH levels for poor response was 1.05 ng/mL (receiver operating characteristic [ROC] curves/area under the curve [AUC], $ROC_{AUC}$=0.85, sensitivity 74%, specificity 87%). Hyper response cut-off value was 3.55 ng/mL $ROC_{AUC}$=0.91, sensitivity 94%, specificity 81%). When the study group was divided according to the serum AMH levels (low: <1.05 ng/mL, middle: 1.05 ng/mL - 3.55 ng/mL, high: >3.55 ng/mL), the groups showed no statistical differences in mature oocyte rates (71.6% vs. 76.5% vs. 74.8%) or fertilization rates (76.9% vs. 76.6% vs. 73.8%), but showed significant differences in clinical pregnancy rates (21.7% vs. 24.1% vs. 40.8%, $p$=0.017). Conclusion: The serum AMH level can be used to predict the number of oocytes retrieved in patients, distinguishing poor and high responders.

• Journal of Life Science
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• v.19 no.7
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• pp.934-942
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• 2009

This study was performed to observe the effect of hot-water extracts from garlic and 13 kinds of medicinal plants composites (GMP) on hyperlipidemia and hepatoprotective activity in rats administered with alcohol. Male Sprague-Dawly rats were fed an AIN-93 diet (Normal), a normal diet plus ethanol (control, 10 ml of 40% ethanoljkgjday), a control diet plus 0.5% garlic and 1.0% medicinal plants composites extracts (GMP-I), and a control diet plus 1.0% garlic and medicinal plants composites extracts (GMP-II) for 7 days. Blood glucose was higher than the control, but it was markedly decreased in the GMP-II group. Elevation total lipids, cholesterol, triglyceride and phospholipids in serum were markedly decreased in rats fed with GMP-I. GMP-II also inhibited the increase of lipid content in serum. Activities of GOT, GPT, $\gamma$-GTP and ALP in serum elevated by alcohol were significantly inhibited in the GMP group. TBARS content of serum was significantly decreased in GMP groups administered with garlic and medicinal plant extracts. Extracts of garlic and medicinal plants play an important role in recovering liver function in rats from alcohol induced damage.