Myricetin Suppresses Ovarian Cancer In Vitro by Activating the p38/Sapla Signaling Pathway and Suppressing Intracellular Oxidative Stress.

Ovarian cancer is a common malignancy with a mortality and effective, efficient treatments are urgently needed. Myricetin (Myr) is a flavonoid with antioxidant and anticancer properties. Here, we assessed Myr's toxicity on the non-tumor cell line, IOSE-80 and the mechanism by which it suppresses proliferation, migration, and invasion of ovarian cancer SKOV3 cells. The effects of Myr on SKOV3 cells were assessed using CCK-8, oxidative stress, wound healing, Transwell, Hoechst 33258 staining, and western blot assays. Our data show that although Myr was not toxic against IOSE-80 cells for a range of concentrations 0-40µM, it suppressed SKOV3 cell proliferation, migration, and invasion and enhanced apoptosis. Mechanistically, it activated the p38/Sapla signaling pathway, thereby inhibiting oxidative stress and reducing the level of ROS in tumor cells. Our data show that Myr suppresses ovarian cancer cells in vitro and suggests Myr as a candidate agent against ovarian cancer.

MicroRNA-129-1-3p Represses the Progression of Triple-Negative Breast Cancer by Targeting the GRIN2D Gene.

The aberrant expression of miRNA is strongly linked to numerous stages of triple-negative breast cancer (TNBC) progression, and it plays an indispensable role in the process from tumor onset and progress to invasion and metastasis. In this study, we first transfected miR-129-1-3p mimics and inhibitor into MDA-MB-231 TNBC cells, respectively. Then, we assessed the pathological role of miR-129-1-3p in MDA-MB-231 cells. The results showed that miR-129-1-3p were successfully inserted into MDA-MB-231 cells. Besides, miR-129-1-3p could distinctively repress the growth, migration along with infiltration of MDA-MB-231 cells, which might be related to the inhibition of GRIN2D expression. Our results indicate that miR-129-1-3p was illustrated to serve as a tumor repressor via targeting GRIN2D in TNBC cells and highlight that the restoration of miR-129-1-3p might be a new treatment target for TNBC.

Knockdown of long non-coding RNA HOTAIR reverses cisplatin resistance of ovarian cancer cells through inhibiting miR-138-5p-regulated EZH2 and SIRT1.

BACKGROUND: Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. METHODS: DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. RESULTS: We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. CONCLUSIONS: These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.

How to judge pelvic malposition when assessing acetabular index in children? Three simple parameters can determine acceptability.

BACKGROUND: The acetabular index (AI) is the most commonly used parameter for diagnosing hip dysplasia. Pelvic malposition can result in misinterpretation of AI measurement especially in younger children. We aimed to investigate the correlation between pelvic orientation and acetabular index (AI) by using digital reconstructed radiographs (DRRs) and identify reliable parameters predictive of pelvic orientation on plain radiographs. METHODS: We retrospectively identified 33 children (52 hips) who received dual source CT examinations. Virtual pelvic models were reconstructed after scanning. After orientating in the standard neutral position, the models were rotated and tilted around corresponding axes. DRRs were generated at every 3° during the process. The acetabular index, the horizontal diameter (Dh) and vertical diameter (Dv) of bilateral obturator foramina, the vertical distance (h) between upper border of pubic symphysis, and Hilgenreiner's line were measured on each DRR by two independent observers. Rotation index (Rr = right Dh/left Dh), tilt index (Rt = h/Dv), intra-observer error, and inter-observer error of AI were calculated. RESULTS: For tilt and rotation up to 12.0°, AI increased with anterior tilt and decreased with posterior tilt. And for rotation, it increased on the side toward which the pelvis rotated and decreased on the opposite side. AI varied dramatically if angulation exceeded 6.0°. Malposition below this limit demonstrated the intra- and inter-observer errors were ± 2.0° and ± 3.0° respectively and caused no significant effect on AI measurement. CONCLUSIONS: For children up to age 6 years, an acceptable pelvic plain radiograph can be determined when Rt is approximately between 0.9 and 1.4 and Rr between 0.7 and 1.5. For the first time, we have identified parameters derived from a group of subjects which can predict this degree of malposition. The parameters obturator diameters (Dh), obturator height (Dv), and distance (h) between symphysis and Hilgengreiner's line can be feasibly measured on X-ray and employed in clinical practice to assess the acceptability of the pediatric pelvic radiograph prior to measurement of the AI.

Knockdown of long non-coding RNA HOTAIR reverses cisplatin resistance of ovarian cancer cells through inhibiting miR-138-5p-regulated EZH2 and SIRT1

BACKGROUND: Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. METHODS: DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. RESULTS: We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. CONCLUSIONS: These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.

P38 Signal Transduction Pathway Has More Cofactors on Apoptosis of SGC-7901 Gastric Cancer Cells Induced by Combination of Rutin and Oxaliplatin.

Currently, gastric cancer treatment is mainly based on first-line intervention with oxaliplatin (OXA) after surgical resection, but the application of OXA has been limited due to the toxic side effects caused by the cumulative dose. The toxicity of OXA mainly includes hepatotoxicity, nephrotoxicity, and ototoxicity, and there is an urgent clinical need to find alternatives that are less toxic and more effective. Rutin (RT) is a natural flavonoid with many biological activities. Studies have found that RT inhibits tumor cell growth and enhances their sensitivity toward certain drugs. As the underlying impact of RT on gastric cancer and its molecular mechanism remain poorly understood, we performed a series of experiments to determine whether RT has the effect of treating gastric cancer, and whether it can cooperate with OXA to treat gastric cancer and its related mechanisms. In the present study, we founded that RT suppressed cell viability, inhibited cell proliferation by causing G0/G1 arrest, and induced apoptosis in SGC 7901 cells. And RT can play as an antitumor agent together with OXA. The mechanism of RT-induced apoptosis may be associated with the activation of the p38/Caspase signal pathway. These results demonstrated the potential of RT as a promising therapeutic compound to treat gastric cancer. At the same time, RT can synergize with OXA to reduce the dose of OXA and reduce the toxicity.

Meta-analysis of the diagnostic value of contrast-enhanced ultrasound for the detection of vascular complications after liver transplantation

Background: contrast-enhanced ultrasound (CEUS) is increasingly used to identify vascular complications in patients after liver transplantation. The present study aimed to evaluate the diagnostic accuracy of CEUS using all available data. Materials and methods: relevant studies published before February 2018 were retrieved from PubMed, EMBASE, ScienceDirect and Web of Science. Pooled sensitivity and specificity, diagnostic odds ratio (DOR) and summary receiver operating characteristic curve (SROC) were calculated to estimate the diagnostic performance of CEUS for vascular complications. Sensitivity analysis was performed that stratified studies according to age, study design and sample size in order to determine the influence of these factors on the overall effect. Meta-regression analyses were performed to examine the possible sources of heterogeneity. Quality assessment and publication bias of the included studies were also evaluated. Results: thirteen studies which consisted of 2,781 CEUS cases were included in the analysis. The pooled weighted estimates of sensitivity and specificity were 0.90 (95% CI, 0.84 to 0.95) and 1.00 (95% CI, 1.00 to 1.00), the diagnostic odds ratio (DOR) was 431.96 (95% CI, 164.60 to 1,133.59) and the area under the curve (AUC) of SROC was 0.9741. According to the sensitivity analysis, age, study design and sample size had an insignificant influence on the diagnostic performance of CEUS. The meta-regression analyses did not reveal a strong correlation between CEUS accuracy and study design, treatment time of patients and experience of the radiologists. Conclusion: the results of our meta-analysis showed a high sensitivity, specificity and accuracy of the CEUS modality for the identification of vascular complications in patients after liver transplantation. Since this is the first meta-analysis investigating in this aspect, more evidence is required to validate the clinical utility of CEUS for the identification of vascular complications in patients with a transplanted liver

No disponible

Meta-analysis of the diagnostic value of contrast-enhanced ultrasound for the detection of vascular complications after liver transplantation.

BACKGROUND: contrast-enhanced ultrasound (CEUS) is increasingly used to identify vascular complications in patients after liver transplantation. The present study aimed to evaluate the diagnostic accuracy of CEUS using all available data. MATERIALS AND METHODS: relevant studies published before February 2018 were retrieved from PubMed, EMBASE, ScienceDirect and Web of Science. Pooled sensitivity and specificity, diagnostic odds ratio (DOR) and summary receiver operating characteristic curve (SROC) were calculated to estimate the diagnostic performance of CEUS for vascular complications. Sensitivity analysis was performed that stratified studies according to age, study design and sample size in order to determine the influence of these factors on the overall effect. Meta-regression analyses were performed to examine the possible sources of heterogeneity. Quality assessment and publication bias of the included studies were also evaluated. RESULTS: thirteen studies which consisted of 2,781 CEUS cases were included in the analysis. The pooled weighted estimates of sensitivity and specificity were 0.90 (95% CI, 0.84 to 0.95) and 1.00 (95% CI, 1.00 to 1.00), the diagnostic odds ratio (DOR) was 431.96 (95% CI, 164.60 to 1,133.59) and the area under the curve (AUC) of SROC was 0.9741. According to the sensitivity analysis, age, study design and sample size had an insignificant influence on the diagnostic performance of CEUS. The meta-regression analyses did not reveal a strong correlation between CEUS accuracy and study design, treatment time of patients and experience of the radiologists. CONCLUSION: the results of our meta-analysis showed a high sensitivity, specificity and accuracy of the CEUS modality for the identification of vascular complications in patients after liver transplantation. Since this is the first meta-analysis investigating in this aspect, more evidence is required to validate the clinical utility of CEUS for the identification of vascular complications in patients with a transplanted liver.

Urotensin II enhances transforming growth factor­ß1 expression and secretion in the kidney during aristolochic acid nephropathy.

Aristolochic acid is a component of many types of Chinese medicine, which are commonly used to treat almost all human diseases. However, aristolochic acid may cause nephropathy. Urotensin II (UII) and transforming growth factor (TGF)­ß1 are important signaling factors, which are expressed at elevated levels during the development of nephropathy. However, the association between UII and TGF­ß1 expression remains unclear. In the current study, the regulatory association between UII and TGF­ß1 expression was investigated using a rat aristolochic acid nephropathy model and the NRK­52E cell line. The expression levels of UII and TGF­ß1 were identified to be constantly increased in the rat aristolochic acid nephropathy model, even 10 days after administration of Aristolochiae manshuriensis decoction was terminated. Notably, increases in the TGF­ß1 expression levels occurred later than those of UII. Furthermore, UII enhanced TGF­ß1 expression in, and secretion from, NRK­52E cells. These data indicate that UII and TGF­ß1 are important in the development of aristolochic acid nephropathy, and UII enhances TGF­ß1 expression levels and secretion during aristolochic acid nephropathy. However, the underlying mechanisms for the precise roles of UII and TGF­ß1 as well as the method by which UII regulates the expression TGF­ß1 in aristolochic acid nephropathy remain to be elucidated in future studies.

Low expression of PKCα and high expression of KRAS predict poor prognosis in patients with colorectal cancer.

The current study aimed to determine the association between protein kinase Cα (PKCα) and Kirsten rat sarcoma viral oncogene homolog (KRAS) expression and the response to folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX regimen) in patients with colorectal cancer (CRC). The protein levels of PKCα and KRAS were analyzed by immunohistochemistry in tissue samples from patients with CRC and in non-cancerous tissues, including 152 cases of colorectal adenocarcinoma, 30 cases of colorectal adenoma and 20 normal colonic mucosa samples. The association between PKCα and KRAS expression and clinicopathological features was analyzed. The rates of positive PKCα protein expression in patients with poorly, moderately and well-differentiated adenocarcinoma were 16.7% (6/36), 40.0% (24/60), and 57.1% (32/56), respectively (P<0.013). The rate of positive KRAS expression in CRC patients was significantly higher than in patients with colon adenoma and normal colon mucosa (P<0.001). Expression levels of KRAS were associated with the degree of differentiation of CRC (P<0.001). Expression of PKCα was negatively correlated with KRAS expression in CRC tissues. The mean progression-free survival (PFS) times in patients with high and low expression of PKCα were 43.9 and 38.8 months, respectively (P<0.001). The mean PFS times were 38.5 and 45.5 months in patients with high and low expression of KRAS, respectively (P=0.001). In conclusion, low PKCα and high KRAS expression predicted relatively poor prognosis in patients with CRC.

Serum B-type natriuretic peptide levels as a marker for anthracycline-induced cardiotoxicity.

Observational and experimental studies have produced inconsistent evidence about the association of serum levels of B-type natriuretic peptide (BNP) with anthracycline-induced cardiotoxicity (AIC). Therefore, the current meta-analysis examined the association between serum BNP levels and AIC by using data from high quality studies published in peer-reviewed journals. Relevant studies were identified through literature searches of China National Knowledge Infrastructure (CNKI), Web of Science, PubMed, Google Scolar and China BioMedicine (CBM). STATA software was used in this meta-analysis for statistical analysis. In addition, the crude standardized mean difference (SMD) with 95% confidence interval (CI) for the highest vs. the lowest category of serum BNP levels was calculated. A total of 8 independent case-control studies, containing 126 AIC patients and 569 healthy controls, were included for the current meta-analysis. The results indicated a significant difference in serum BNP levels between the cardiotoxic group and normal group, with respect to post-treatment and pretreatment with anthracyclines. Specifically, the serum levels of BNP increased remarkably after treatment with anthracyclines in the cardiotoxic group, compared with the normal group. No publication bias was detected in this meta-analysis. The findings of the present study provide strong evidence that serum BNP levels may be associated with AIC.

Surgical treatment of granulomatous mastitis associated with autoimmune response.

Granulomatous mastitis (GM) is a rare breast disease with unknown etiology. Clinical management strategies for GM include surgery, antibiotics, and steroid treatments. As patients with GM often respond to steroids, GM is thought to be an autoimmune disease. Here we describe a case of trauma-induced GM that presented as autoimmune disease but was successfully treated by surgery without steroids. The patient showed no sign of recurrence for 11 months. This case provides useful information on both the underlying mechanisms and clinical management of GM.