INSR gene polymorphisms correlate with sensitivity to platinum-based chemotherapy and prognosis in patients with epithelial ovarian cancer.

This study aimed to investigate the correlation between INSR gene polymorphisms on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy were recruited for the study. Tag single-nucleotide polymorphism of INSR gene was screened from HapMap combined with available literature. Frequency distribution of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed less platinum-based chemotherapy sensitivity in EOC patients (odds ratio (OR)=0.269, 95% confidence interval (CI)=0.159~0.456; OR=0.445, 95% CI=0.214~0.926, respectively), as well as serous EOC patients (OR=0.083, 95% CI=0.024~0.278; OR=0.235, 95%CI=0.053~1.041, respectively). The clinical characteristics including age, clinical stage, histological grade and residual lesion size were significantly related with chemosensitivity to platinum drugs and mortality in EOC patients. According to Kaplan-Meier curve, compared with CC+GC genotype, rs2252673 GG genotype showed significantly decreased survival rate in EOC patients (P<0.05). Cox regression model indicated that rs2252673, age and clinical stage were independent risk factors for the prognosis in EOC (all P<0.05). These findings indicate that INSR rs2252673 and rs3745546 polymorphisms were associated with sensitivity to platinum-based chemotherapy in EOC patients and rs2252673 polymorphism may be an independent risk factor for EOC prognosis.

Retraction Note: LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A.

The article "LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A, by C.-C. Hu, Y.-W. Liang, J.-L. Hu, L.-F. Liu, J.-W. Liang, R. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6602-6611-DOI: 10.26355/eurrev_201908_18548-PMID: 31378902" has been retracted by the authors. After publication, the article was questioned on PubPeer. Concerns were raised about Figure 2, Table I, and the reliability of the published results. The same authors stated that they want to rearrange the manuscript and provide readers with a more precise model. https://www.europeanreview.org/article/18548.

A J-shaped relationship between the atherogenic index of plasma and new-onset myocardial infarction in hypertensive patients with obstructive sleep apnea: a cohort study.

OBJECTIVE: This study aimed to investigate the relationship between baseline atherogenic index of plasma (AIP) and new-onset myocardial infarction (MI) in hypertensive patients with obstructive sleep apnoea (OSA). PATIENTS AND METHODS: 2,281 participants were included in this analysis after strict adherence to the inclusion and exclusion criteria. Hazard ratio (HR) and 95% confidence interval (CI) were estimated using multivariable Cox regression models. A generalized additive model was employed to determine nonlinear relationships. RESULTS: In multivariate-adjusted models, there was a positive association between AIP and new-onset MI (per SD increase; HR=1.42, 95% CI: 1.22-1.65). Smoothing curve fitting revealed a J-shaped association between AIP and new-onset MI, with a turning point of approximately -0.08. The addition of AIP to a model with established risk factors improved the C-index (p=0.007), integrated discrimination improvement (p=0.007), and continuous net reclassification improvement (p=0.027) for the new-onset MI. CONCLUSIONS: A J-shaped relationship was observed between AIP and new-onset MI.

LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A.

OBJECTIVE: To clarify the potential function of long non-coding RNA (lncRNA) RUSC1-AS1 in regulating the progression of breast cancer (BCa) and the underlying mechanism. PATIENTS AND METHODS: RUSC1-AS1 level in BCa tissues and adjacent normal tissues was first determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between RUSC1-AS1 expression with tumor size, clinical stage and overall survival of BCa patients was analyzed. Influences of RUSC1-AS1 knockdown on viability, clonality, cell cycle and apoptosis of BCa cell lines MCF-7 and BT549 were evaluated. Target genes of RUSC1-AS1 were predicted by bioinformatics, and their interaction was further confirmed by RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and rescue experiments. RESULTS: A higher abundance of RUSC1-AS1 was identified in BCa tissues relative to controls. The expression level of RUSC1-AS1 was positively correlated to tumor size and clinical grade, but negatively correlated to the overall survival of BCa patients. The silence of RUSC1-AS1 markedly inhibited viability, clonality, cell cycle progression, and induced apoptosis of MCF-7 and BT549 cells. Finally, CDKN1A and KLF2 were found to be the target genes of RUSC1-AS1, which were tumor-suppressor genes involved in RUSC1-AS1-mediated BCa progression. CONCLUSIONS: RUSC1-AS1 is highly expressed in BCa, which promotes the progression of BCa through mediating CDKN1A and KLF2. RUSC1-AS1 may serve as a potential hallmark for BCa.

Effect of miR-130a on neuronal injury in rats with intracranial hemorrhage through PTEN/PI3K/AKT signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of micro-ribonucleic acid (miR)-130a on neuronal injury in rats with intracerebral hemorrhage (ICH) through the phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway. MATERIALS AND METHODS: A total of 30 healthy male rats were randomly divided into three groups, including the blank control group, ICH model group (ICH group) and ICH model + miR-130a treatment group (miR-130a treatment group). The differences in neurological injury, the number of apoptotic cells in brain tissues, the activity of Caspase-9 and protein expressions of PTEN/PI3K/AKT were analyzed among the three groups, respectively. RESULTS: Neurological function was normal without injury in the control group. However, the neurological injury was severe in the ICH group and mild in the miR-130a treatment group. There were statistically significant differences in neurological function in the control group relative to those of the ICH group and miR-130a treatment group (p<0.05). Meanwhile, the neurological injury was markedly milder in the miR-130a treatment group than that of the ICH group, showing a statistically significant difference (p<0.05). The number of apoptotic cells was remarkably smaller in the control group when compared with the ICH group and miR-130a treatment group. However, it was markedly larger in the ICH group than that of the miR-130a treatment group, showing significant differences (p<0.05). The activity of Caspase-9 was significantly lower in the control group than ICH group and miR-130a treatment group (p<0.05). However, it increased remarkably in the ICH group compared with that of the miR-130a treatment group (p<0.05). Moreover, the protein level of PTEN in the ICH group was significantly higher than control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, no marked difference in the protein level of PTEN was observed between the control group and miR-130a treatment group (p>0.05). The protein levels of the phosphorylated 3-hydroxy kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) were remarkably lower in the ICH group than those of the control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, they were remarkably higher in the miR-130a treatment group than that of the control group (p<0.05). CONCLUSIONS: MiR-130a promotes neuronal growth in brain tissues in ICH rats and alleviates neuronal injury after ICH through the PTEN/PI3K/AKT signaling pathway. Our findings suggest that miR-130a exerts important clinical significance in the treatment of ICH.

Simvastatin alleviates inflammation and oxidative stress in rats with cerebral hemorrhage through Nrf2-ARE signaling pathway.

OBJECTIVE: To investigate the regulatory effects of simvastatin on the inflammation and oxidative stress in rats with cerebral hemorrhage through the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway. MATERIALS AND METHODS: A total of 120 healthy male rats weighing 280-300 g and 7-8 weeks old were selected to establish the traumatic brain injury (TBI) model. Rats were divided into group A (trauma operation, n=30), group B (no treatment, n=30), group C (drug administration after trauma operation, n=30), and group D (no trauma operation, drug administration, n=30). Cerebral edema content in brain tissues was measured by calculating the dry and wet weight. Neurological dysfunction was scored using the Garcia method. Positive levels of the Toll-like receptor 4 (TLR4) and interleukin-1ß (IL-1ß) were qualitatively analyzed via immunohistochemistry. Protein levels of TLR4 and IL-1ß were quantitatively analyzed via Western blotting. Moreover, the brain injury volume and neuronal apoptosis were evaluated via Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. At 48 h after injury, activities of superoxide dismutase (SOD), reduced glutathione (GSH), and oxidized glutathione (GSSG) in brain tissues were detected, and levels of malondialdehyde (MDA) and nitric oxide (NO) were detected using the enzyme activity assay kits. Finally, relative levels of the Nrf2-ARE signaling pathway and its downstream molecules heme oxygenase-1 (HO-1) and NAD (P)H dehydrogenase, quinone 1 (NQO1) were detected via reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: Compared with those in group B, cerebral edema content in brain tissues significantly increased (p<0.05), the neurological dysfunction score significantly declined (p<0.05), and protein levels of TLR4 and IL-1ß were significantly upregulated in group A (p<0.05). In group C, relative levels of TLR4 and IL-1ß were down-regulated, cerebral edema content decreased, and the neurological dysfunction score significantly increased (p<0.05). After 48 h, activities of SOD, reduced GSH and GSSG and levels of MDA and NO all increased, and levels of MDA and NO declined in group C (p<0.05). Western blotting and RT-PCR showed that simvastatin could increase the transcriptional level of Nrf2. After simvastatin intervention, expression levels of downstream molecules HO-1 and NQO1 were upregulated. CONCLUSIONS: Simvastatin alleviates TLR4-mediated inflammatory injury, promotes neurological recovery and resists oxidative stress through the Nrf2-ARE signaling pathway, thus exerting a neuroprotective effect in TBI.

Low expression of miR-1231 in patients with glioma and its prognostic significance.

OBJECTIVE: MiR-1231 has been reported to be down-regulated in glioma tissues and to act as a negative regulator in glioma progression. However, the clinical significance of miR-1231 remains unclear. In this study, we aimed to further demonstrate the expression pattern and prognostic value of miR-1231 in glioma patients. PATIENTS AND METHODS: We determined the expression level of miR-1231 in 154 cases of paired glioma and adjacent non-tumor tissues by quantitative Real Time-PCR (qRT-PCR). The association between miR-1231 expression levels and clinicopathological factors was examined by the χ2 test. The Kaplan-Meier survival analysis was performed to analyze the association of miR-1231 expression with overall survival (OS) and progression-free survival (PFS) of patients. The significance of survival variables was analyzed using the Cox multivariate proportional hazards model. RESULTS: We found that the expression level of miR-1231 in human glioma tissues was significantly lower than that in the adjacent nontumorous tissues (p<0.01). The expression levels of miR-1231 in glioma tissues with high grades were significantly lower than those with low grades. Decreased miR-1231 expression was significantly associated with advanced WHO grade (p=0.001) and KPS score (p=0.023). The Kaplan-Meier analysis indicated that low miR-1231 expression had a significant impact on OS (p=0.0103) and PFS (p=0.0019). Cox proportional hazards risk analysis demonstrated that miR-1231 was an independent prognostic factor for glioma. CONCLUSIONS: Our study, for the first time, provides evidence that evaluating miR-1231 in glioma may have prognostic and predictive value in the clinical management of glioma.

Correlation of serum PCSK9 in CHD patients with the severity of coronary arterial lesions.

OBJECTIVE: The present study aims to investigate the correlation between serum level of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the severity of coronary arterial lesion in patients with coronary heart disease (CHD). PATIENTS AND METHODS: Between August 2010 and January 2015, 126 CHD patients and 70 patients with coronary arterial stenosis < 50% (controls) were included in the present study. Serum PCSK9 level was determined using ELISA. Demographic characteristics, relevant clinical data and biochemical data were collected from all patients, and their relationship with PCSK9 was analyzed to evaluate the correlation of PCSK9 expression with the severity of coronary artery disease (CAD). RESULTS: Concentrations of total cholesterol (TC) and fasting blood sugar (FBS) were significantly higher in CHD patients than in controls (p < 0.05). No significant differences were observed in gender, age, body mass index (BMI), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), family history, smoking history and history of hypertension between groups (p > 0.05). Serum PCSK9 levels in the CHD group were significantly higher than those in the control group [(96.4 ± 33.2) ng/mL vs. (81.8 ± 27.6) ng/mL, p < 0.05]. Compared with those of patients with single-vessel or double-vessel disease, PCSK9 levels were significantly elevated in patients with multi-vessel disease (p < 0.05). The Gensini score of the CHD group was significantly lower than that of the control group (11.4 ± 10.5 vs. 37.3 ± 10.3, p < 0.05). The Gensini score of patients with multi-vessel disease was significantly higher compared with patients of single-vessel  or double-vessel disease (p < 0.05). Correlation analysis revealed that PCSK9 was positively correlated with many clinical parameters, including age, BMI, TC, TG, systolic blood pressure, FBS, Gensini score and LDL-C (p < 0.05). However, PCSK9 was not correlated with either gender ratio or diastolic blood pressure (p > 0.05). CONCLUSIONS: Serum PCSK9 level is significantly elevated in CHD patients and its variation is correlated with the severity of CAD.

Far upstream element-binding protein 1 is a prognostic biomarker and promotes nasopharyngeal carcinoma progression.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor with tremendous invasion and metastasis capacities, and it has a high incidence in southeast Asia and southern China. Previous studies identified that far upstream element-binding protein 1 (FBP1), a transcriptional regulator of c-Myc that is one of the most frequently aberrantly expressed oncogenes in various human cancers, including NPC, is an important biomarker for many cancers. Our study aimed to investigate the expression and function of FBP1 in human NPC. Quantitative real-time RT-PCR (qRT-PCR), western blot and immunohistochemical staining (IHC) were performed in NPC cells and biopsies. Furthermore, the effect of FBP1 knockdown on cell proliferation, colony formation, side population tests and tumorigenesis in nude mice were measured by MTT, clonogenicity analysis, flow cytometry and a xenograft model, respectively. The results showed that the mRNA and protein levels of FBP1, which are positively correlated with c-Myc expression, were substantially higher in NPC than that in nasopharyngeal epithelial cells. IHC revealed that the patients with high FBP1 expression had a significantly poorer prognosis compared with the patients with low expression (P=0.020). In univariate analysis, high FBP1 and c-Myc expression predicted poorer overall survival (OS) and poorer progression-free survival. Multivariate analysis indicated that high FBP1 and c-Myc expression were independent prognostic markers. Knockdown of FBP1 reduced cell proliferation, clonogenicity and the ratio of side populations, as well as tumorigenesis in nude mice. These data indicate that FBP1 expression, which is closely correlated with c-Myc expression, is an independent prognostic factor and promotes NPC progression. Our results suggest that FBP1 can not only serve as a useful prognostic biomarker for NPC but also as a potential therapeutic target for NPC patients.

Pharmaco-induced erections for penile color-duplex ultrasound: oral PDE5 inhibitors or intracavernosal injection?

To prospectively compare the clinical responses and penile color-duplex ultrasound (PCDU) results of oral PDE5 inhibitors (PDE5-Is) with papaverine intracavernosal injection (ICI) and to evaluate whether PDE5-Is could be used as alternatives to vasoactive agent injections, 25 ED patients underwent PCDU three times with an interval of at least 1 week, using different pharmacological induction: ICI mode (30-60 mg papaverine), sildenafil mode (100 mg sildenafil) and tadalafil mode (20 mg tadalafil). The preference of the patients was collected when all tests were completed. No significant differences were found in peak systolic velocity and acceleration time among all three modes. However for the ICI mode, end diastolic velocity of the right cavernosal artery was significantly higher than those of the sildenafil and tadalafil modes 5 min after erection induction, and at 15 min it became lower than those of two PDE5-I modes. Consequently, resistance index of the right cavernosal artery in ICI mode was reversed at 5 and 15 min. In all, 60.0 and 56.0% patients managed to reach full erection in PDE5-Is modes, which was significantly lower than in ICI mode (80.0%). Therefore, although PDE5-Is and papaverine ICI showed similar effects on PCDU parameters in detecting arterial ED, more patients had better clinical responses to ICI, and oral PDE5-Is administration still showed some pitfalls in practical use.