Retraction Note: MiR-221 inhibits proliferation of pancreatic cancer cells via down regulation of SOCS3.

The article "MiR-221 inhibits proliferation of pancreatic cancer cells via down regulation of SOCS3", by J. Xie, J.-T. Wen, X.-J. Xue, K.-P. Zhang, X.-Z. Wang, H.-H. Cheng, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 1914-1921-DOI: 10.26355/eurrev_201804_14714-PMID: 29687843 has been retracted by the Editor in Chief for misconduct and data fabrication. An investigation conducted by the National Health Commission of the People's Republic of China, determined that the information and images presented in the paper have been manipulated, pieced together, and subjected to various fraudulent alterations. Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the articles. The corresponding authors did not respond to journal correspondence about the investigation and retraction of this article. This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14714.

Effectiveness of intra-operative ultrasonography, compared to conventional techniques, in attaining tumour free lumpectomy margins in breast cancer: a meta-analysis.

OBJECTIVE: The aim of the study was to summarize and update evidence on whether intra-operative ultrasonography (IOUS) guided breast conserving surgery (BCS) can be more effective than wire-guided or palpation-guided excision for both nonpalpable, as well as palpable breast cancers in achieving tumor free negative margins after lumpectomy for breast cancer. MATERIALS AND METHODS: Comprehensive searches were done systematically through PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases. Statistical analysis was done using STATA version 13.0. The primary outcome was proportion of patients that achieved tumor free resection margins after lumpectomy. Effect sizes were reported as pooled relative risks (RR). All estimates were reported with 95% confidence intervals (CI). RESULTS: A total of 20 RCTs with 2519 participants were included in the meta-analysis. Use of intra-operative ultrasonography was associated with 1.18 times higher chances [RR 1.18; 95% CI, 1.10-1.27] of attaining a tumor free margin for all breast cancers, 1.16 times higher chances [RR 1.16; 95% CI, 1.10-1.23] of attaining a tumor free margin for all palpable breast cancers and 1.20 times higher chances [RR 1.20; 95% CI, 1.05-1.38] of attaining a tumor free margin for all non-palpable breast, compared to wire guided or palpation guided localization. There was no evidence of publication bias. CONCLUSIONS: The findings support that intra-operative ultrasonography increases the chances of obtaining negative margins for tissue resected in breast conserving surgeries. The findings support the observations of previous reviews published in this aspect nearly half a decade back.

MiR-126 facilitates apoptosis of retinal ganglion cells in glaucoma rats via VEGF-Notch signaling pathway.

OBJECTIVE: The aim of this study was to explore the effect of micro ribonucleic acid (miR)-126 on the apoptosis of retinal ganglion cells in glaucoma rats via the vascular endothelial growth factor (VEGF)-Notch signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley (SD) rats were randomly divided into three groups, including normal group (n=12), model group (n=12) and miR-126 antagomir group (n=12). Rats in normal group did not receive any treatment. In model group and miR-126 antagomir group, the rats were used to establish glaucoma models and intervened with normal saline and miR-126 antagomir, respectively. Intraocular pressure was detected at the completion of modeling and the last intervention, at 7 days after which samples were taken. Western blotting was adopted to detect the relative protein expressions of Notch1 and Notch2. The content of VEGF was examined via enzyme-linked immunosorbent assay (ELISA). Quantitative polymerase chain reaction (qPCR) was carried out to detect the messenger RNA (mRNA) expressions of VEGF, Notch1 and Notch2. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to detect cell apoptosis. RESULTS: After modeling, intraocular pressure in model group and miR-126 antagomir group was significantly higher than that in normal group (p<0.05). At the end of the intervention, intraocular pressure in miR-126 antagomir group was notably lower than that in model group (p<0.05). VEGF content in model group and miR-126 antagomir group was notably higher than that in normal group (p<0.05). However, it was markedly lower in miR-126 antagomir group than model group (p<0.05). Model group exhibited remarkably higher protein expressions of Notch1 and Notch2 than normal group (p<0.05). However, the protein expressions of Notch1 and Notch2 in miR-126 antagomir group were evidently reduced (p<0.05). Besides, the mRNA expressions of VEGF, Notch1 and Notch2 in model group were significantly higher than those in normal group (p<0.05). However, they were significantly lower in miR-126 antagomir group than those in model group (p<0.05). Furthermore, the apoptosis rate in model group was distinctly higher than that in normal group (p<0.05). However, it was notably lower in miR-126 antagomir group than model group (p<0.05). CONCLUSIONS: MiR-126 facilitates the apoptosis of retinal ganglion cells in glaucoma rats by promoting the VEGF-Notch signaling pathway.

Perindopril inhibits myocardial apoptosis in mice with acute myocardial infarction through TLR4/NF-κB pathway.

OBJECTIVE: To explore the anti-apoptotic effect of perindopril on myocardial cells in mice with acute myocardial infarction (AMI). MATERIALS AND METHODS: A total of 48 mice were randomly divided into 4 groups before intervention, namely sham operation group (Sham group, n=12), AMI group (n=12), 1.5 mg/kg perindopril treatment group (Perindopril group, n=12), and 1.5 mg/kg perindopril treatment and Toll-like receptor-4 (TLR4) knockout group (TLR4-/-Perindopril group, n=12). Mice in the control group and AMI group were gavaged with normal saline, and those in the Perindopril group and TLR4-/-Perindopril group were gavaged with perindopril for 7 d. On the 4th day after drug administration, mice in the AMI group, Perindopril group and TLR4-/-Perindopril group were subjected to the ligation of the anterior descending coronary artery to induce AMI, and those in the Sham group underwent the same operation, but had a loose knot at the anterior descending coronary artery. At 24 h after the above operation, color echocardiography was performed on mice to observe changes in cardiac function. Then, the mice were sacrificed. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) assay was carried out to determine myocardial apoptosis. Immunohistochemistry and Western blotting technique were employed to detect the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p50 in infarction zones. The messenger ribonucleic acid (mRNA) expression levels of TLR4 and NF-κB p50 in infarction zones were measured via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). RESULTS: Perindopril could significantly reduce the number of apoptotic myocardial cells after AMI. Mouse echocardiography showed that ejection fraction (EF), left ventricular fractional shortening (FS), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) of AMI mice in the Perindopril groups were markedly superior to those in the AMI group. AMI mice in the Perindopril group had decreased expression levels of Bax protein and TLR4 and NF-κB p50 mRNA and protein, as well as the Bax/Bcl-2 ratio. Knockout of TLR4 attenuated the effect of perindopril in alleviating myocardial apoptosis after AMI. CONCLUSIONS: Perindopril inhibits myocardial apoptosis in mice with AMI through the TLR4/NF-κB pathway.

MiR-221 inhibits proliferation of pancreatic cancer cells via down regulation of SOCS3.

OBJECTIVE: The over-activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway induced by cytokines are closely correlated with tumorigenesis. Suppressor of cytokine signaling 3 (SOCS3) serves as a negative regulator for JAK-STAT, and its down-regulation is involved in the oncogenesis of pancreatic cancer. We aimed at investigating the effect of miR-221 on the expression and proliferation, cycle and apoptosis of pancreatic cancer cells and determine the related mechanism. PATIENTS AND METHODS: Dual luciferase reporter gene assay was used to analyze the regulation between miR-221 and SOCS3. The expressions of miR-221, SOCS3, p-JAK and p-STAT3 in normal human pancreatic epithelial cell HPDE6-C7 and pancreatic cancer cell PANC-1 were quantified by qPCR and Western blot. Flow cytometry was used to identify cell cycle and proliferation. In vitro cultured PANC-1 cells were transfected with miR-221 inhibitor or pIRES2-SOCS3. The expressions of miR-221, SOCS3, p-JAK and p-STAT3, along with the cell proliferation or apoptosis, were compared. RESULTS: Bioinformatics analysis showed the existence of binding site between miR-221 and 3'-UTR of SOCS3 mRNA. Dual luciferase gene reporter assay confirmed the targeted regulation between miR-221 and SOCS3. Compared to HPDE6-C7 cells, higher levels of miR-221, p-JAK and p-STAT3 expression, and lower expression of SOCS3, were found in PANC-1 cells, along with the increase of cell proliferation. Transfection of miR-221 inhibitor or pIRES2-SOCS3 remarkably enhanced SOCS3 expression, inhibited the levels of p-JAK and p-STAT3 expression, and impeded the proliferation of PANC-1 cells. CONCLUSIONS: MiR-221 decreases proliferation potency of PANC-1 cells and affects JAK-STAT3 signaling pathway via inhibiting SOCS3.

Single nucleotide polymorphisms associated with thermoregulation in lactating dairy cows exposed to heat stress.

Dairy cows with increased rectal temperature experience lower milk yield and fertility. Rectal temperature during heat stress is heritable, so genetic selection for body temperature regulation could reduce effects of heat stress on production. One aim of the study was to validate the relationship between genotype and heat tolerance for single nucleotide polymorphisms (SNPs) previously associated with resistance to heat stress. A second aim was to identify new SNPs associated with heat stress resistance. Thermotolerance was assessed in lactating Holsteins during the summer by measuring rectal temperature (a direct measurement of body temperature regulation; n = 435), respiration rate (an indirect measurement of body temperature regulation, n = 450) and sweating rate (the major evaporative cooling mechanism in cattle, n = 455). The association between genotype and thermotolerance was evaluated for 19 SNPs previously associated with rectal temperature from a genomewide analysis study (GWAS), four SNPs previously associated with change in milk yield during heat stress from GWAS, 2 candidate gene SNPs previously associated with rectal temperature and respiration rate during heat stress (ATPA1A and HSP70A) and 66 SNPs in genes previously shown to be associated with reproduction, production or health traits in Holsteins. For SNPs previously associated with heat tolerance, regions of BTA4, BTA6 and BTA24 were associated with rectal temperature; regions of BTA6 and BTA24 were associated with respiration rate; and regions of BTA5, BTA26 and BTA29 were associated with sweating rate. New SNPs were identified for rectal temperature (n = 12), respiration rate (n = 8) and sweating rate (n = 3) from among those previously associated with production, reproduction or health traits. The SNP that explained the most variation were PGR and ASL for rectal temperature, ACAT2 and HSD17B7 for respiration rate, and ARL6IP1 and SERPINE2 for sweating rate. ARL6IP1 was associated with all three thermotolerance traits. In conclusion, specific genetic markers responsible for genetic variation in thermoregulation during heat stress in Holsteins were identified. These markers may prove useful in genetic selection for heat tolerance in Holstein cattle.

Comparative Study of Three Traditional Mongolian Medicines on Streptozotocin-induced Diabetic Nephropathy in Rats.

3 kinds of prescription of Traditional Mongolian (Chinese) Medicine (TMM) have been used in treating diabetic nephropathy (DN). We aimed to investigate: first, which prescription was more effective; second, whether it was more effective when combined with the 3 prescriptions. The DN model was prepared by a single dose of Streptozotocin (STZ, 65 mg/kg, i.p.) in rats and treated 3 times every day with P-1 (Sugmul-10), P-2 (Narenmandul-11), P-3 (Xieriga-4) respectively, and combined group was treated with P-1 in the morning, P-2 and P-3 in the evening. The results showed combining with 3 prescriptions in one day was much more effective than each single prescription. The mechanism of renal protection maybe related to MMP-2 and TGF-ß1, the conclusion could be useful and beneficial for clinical medicine.

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFß1.

We investigated the effects of the hepatitis B virus X gene (HBV X) on the activation of human hepatic stellate cells (HSCs) and the possible mechanisms underlying the pathway. Recombinant plasmid pHBV-X-IRES2-EGFP was constructed and transfected into HL-7702 cells using a lipid-mediated method. Transfected cells were screened by G418, which detected stable expression of the X gene by reverse transcription (RT)-PCR and Western blot analysis, and named L02/x. Cells not subjected to G418-selection were analyzed to confirm the transient expression of the X gene and named L02/48x. Subsequently, L02/x and L02/48x, together with non-HBx-expressing cells, were co-cultured with HSCs in a non-contact transwell system. After 36 h of co-culture, the proliferation and migration of HSCs was detected using different cell counting methods. Finally, the mRNA and protein levels of α-SMA, Col I, and TGFß1 in HSCs were detected by real-time PCR and western blot analysis. RT-PCR and Western blot analysis showed that L02/x and L02/48x cells can express HBV X gene mRNA and protein. Additionally, HSCs co-cultured with L02/x or L02/48x cells showed significantly higher proliferation and migration levels than control groups. Real-time PCR and Western blot analysis showed that the mRNA and protein expressions of α-SMA, Col I, and TGFß1 in HSCs co-cultured with HBx-expressing liver cells were higher than those in control groups. HBx protein activated HSCs in vitro, leading to increased proliferation and migration of HSCs and upregulation of α-SMA and Col I. The TGFß1 gene may be involved in this pathway.

Plasma chemerin level in metabolic syndrome.

To investigate the chemerin level in the Chinese Han population with metabolic syndrome and its relationship with each metabolic syndrome component [body mass index (BMI), blood pressure, blood lipids, and blood glucose], we selected 30 patients with metabolic syndrome and 30 healthy control subjects. The chemerin level was measured by enzyme immunoassay in these 2 groups. The subjects' weight, blood pressure, BMI, waist circumference, fasting blood glucose, fasting insulin, lipids, and glycated hemoglobin were simultaneously detected. The t-test, correlation analysis, and multiple regression analysis were used to perform statistical analysis. We found that plasma chemerin level was higher in the metabolic syndrome group than that in the control group (97.61 ± 6.49 vs 70.26 ± 6.97, t = 15.73, P < 0.05). The plasma chemerin level was positively correlated with systolic blood pressure, waist circumference, BMI, waist-to-hip ratio, fasting blood glucose, fasting insulin, and glycated hemoglobin (r = 0.548, 0.442, 0.359, 0.556, 0.613, 0.581, and 0.572, respectively; all P < 0.05). However, it was negatively correlated with high-density lipoprotein cholesterol (r = -0.378, P < 0.05). Therefore, we concluded that plasma chemerin level was correlated with obesity, blood pressure, and high-density lipoprotein cholesterol, suggesting that it may play a role in the pathogenesis of metabolic syndrome.

Beta-cypermethrin impairs reproductive function in male mice by inducing oxidative stress.

Cypermethrin (CYP), an insecticide, has deleterious effects on male reproductive function. The objective was to identify whether the effects of beta-CYP on male reproductive organs were associated with oxidative stress. Three doses of beta-CYP (1, 10, and 20mg/kg) were administered to male mice for 35 d, with or without vitamin E (20mg/kg). The moderate (10mg/kg) and high (20mg/kg) doses of beta-CYP not only decreased body weight and the weight of the testes, epididymides, seminal vesicles, and prostate (P<0.05) but also reduced serum testosterone concentration and the expression of steroidogenic acute regulatory protein (P<0.05), in addition to damaging the seminiferous tubules and sperm development. Furthermore, moderate and high doses of beta-CYP administration decreased sperm number, sperm motility, and intact acrosome rate (P<0.05). Based on ultrastructural analyses, high doses of beta-CYP produced swelling and degeneration of mitochondria and the smooth endoplasmic reticulum of Leydig cells and caused the formation of concentric circles. These toxic effects of beta-CYP may be mediated by increasing oxidative stress, as the moderate and high doses of this compound increased malondialdehyde and nitric oxide in testes (P<0.05); reduced the activity of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (P<0.05); and activated ERK1/2 (P<0.05). Vitamin E reversed the effects of beta-CYP on testosterone production and testis damage (P<0.05 vs. the high-dose group). Therefore, we inferred that beta-CYP damaged the structure of testes and decreased sperm output by inducing oxidative stress.

Cesium cholate: determination of X-ray crystal structure indicates participation of the ring hydroxyl groups in metal binding.

The crystal structure of cesium cholate, C(24)H(36)(OH)(3) COOCs has been determined with three-dimensional X-ray diffractometer data. It crystallized in the monoclinic space group P2(1) with unit-cell dimensions a = 11.543(5) A, b = 8.614(3) A, and c = 12.662(5) A, beta(deg) = 107.95(2), V = 1197.7 A(3) and Z = 2. The atomic parameters were refined to a final r = 0.0269 and R(omega) = 0.0280 for 2342 observed reflections. Each Cs(+) is coordinated to 7 oxygen atoms from 5 different cholate anions with Cs-O distances ranging from 2.957(4) A to 3.678(5) A. In this crystal, 5 cholates are coordinated with 1 Cs(+), and 5 Cs(+) are coordinated with 1 cholate anion. Carboxyl and all the 3 ring hydroxyl groups of cholate anion participate in binding to Cs(+) simultaneously, and there is no water molecule coordinated with the Cs(+). The pattern of successive rows arranged with polar (p) and non-polar (n) faces in apposition leads to the formation of a sandwich sheet structure with polar and non-polar channels. The Cs ions lie within the polar interior of the sandwich. The H-bond network is reorganized in forming cesium cholate from cholic acid. All the oxygen atoms in cholate anion are involved in H-bonding reciprocally or with water molecules to form an extensive 3-dimensional network of H-bonds. Compared with cholic acid and other similar type of steroids, the coordination structure and H-bonding of Cs cholate crystal are distinct.