Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression.

Endometriosis is an estrogen-dependent chronic gynecological syndrome. Recent studies have shown that long non-coding RNAs participate in the pathogenesis and development of endometriosis. This study aimed to explore the mechanisms of DHRS4 antisense RNA 1 (DHRS4-AS1) in endometriosis. Dual-luciferase reporter assays were conducted to determine the relationship between DHRS4-AS1, microRNA (miR)-139-5p, and arrestin domain-containing 3 (ARRDC3). Furthermore, the expression of DHRS4-AS1 and miR-139-5p in ectopic endometrial stromal cells (EC-ESCs) and endometriosis tissues was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and Transwell assays were performed to evaluate the proliferation, apoptosis, and migration and invasion of EC-ESCs, respectively. Western blotting and RT-qPCR were further utilized to determine cleaved-Caspase 3, Caspase 3, and matrix metalloproteinase 9 (MMP-9) expression levels. Compared with the EN group, DHRS4-AS1 levels were lower and miR-139-5p levels were higher in EC-ESCs and tissues obtained from patients with endometriosis. Functional assays validated that DHRS4-AS1 targets miR-139-5p, with ARRDC3 being a downstream target of miR-139-5p. Rescue experiments demonstrated that DHRS4-AS1 inhibited EC-ESC proliferation, migration, and invasion, but promoted apoptosis, by targeting miR-139-5p in endometriosis. cleaved-Caspase3 expression level and the cleaved-Caspase 3/Caspase 3 ratio increased, while the expression levels of MMP-9 decreased, after transfection with DHRS4-AS1 overexpression plasmids; however, the effects induced by DHRS4-AS1 overexpression could be partially reversed by co-transfection with the miR-139-5p mimic. The current study demonstrates that the DHRS4-AS1/miR-139-5p/ARRDC3 axis participates in the regulation of EC-ESC function.

circ-AKT3 aggravates renal ischaemia-reperfusion injury via regulating miR-144-5p /Wnt/ß-catenin pathway and oxidative stress.

Renal ischaemia-reperfusion (RI/R) injury is one major pathological state of acute kidney injury (AKI) with a mortality rate ranking 50% to 80%. MiR-144-5p acts as a molecular trigger in various diseases. We presumed that miR-144-5p might be involved RI/R injury progression. We found that RI/R injury decreased miR-144-5p expression in rat models. MiR-144-5p downregulation promoted cell apoptosis rate and activated Wnt/ß-catenin signal in RI/R injury rats. By performing bioinformatic analysis, RIP, RNA pull-down, luciferase reporter experiments, we found that circ-AKT3 sponged to miR-144-5p and decreased its expression in RI/R injury rats. Moreover, we found that circ-AKT3 promoted cell apoptosis rate and activated Wnt/ß-catenin signal, and miR-144-5p mimic reversed the promotive effect of circ-AKT3 in rat models. We also found that circ-AKT3 increased the oxidative stress level in rat models. In conclusion, our study suggests that the circAKT3 is involved RI/R injury progression through regulating miR-144-5p/Wnt/ß-catenin pathway and oxidative stress.

miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A.

Acute kidney injury (AKI) is a common renal dysfunction. Renal ischemia-reperfusion (I/R) injury contributes to AKI progression. The microRNA miR-195-5p can act as a crucial tumor inhibitor in various cancers. However, the potential biological effects of miR-195-5p on AKI are not well-understood. We found that miR-195-5p levels were decreased in the serum samples of patients with AKI. Next, we determined miR-195-5p expression in the renal tissues of the rats and found that it was downregulated. Renal function was evaluated and confirmed using blood urea nitrogen and serum Cr levels. In parallel, the hypoxia-induced NRK-52E cell model was employed, and miR-195-5p was found to be markedly reduced under hypoxic conditions. Furthermore, miR-195-5p was modulated in NRK-52E cells. miR-195-5p induced NRK-52E cell proliferation and protected NRK-52E cells against hypoxia-triggered apoptosis. In an I/R mouse model, miR-195-5p alleviated renal injury triggered by I/R. In addition, oxidative stress and inflammatory factor concentrations were assessed using ELISA. The results showed that miR-195-5p mimicked attenuated oxidative stress induced by I/R injury and downregulated the protein expression of inflammatory factors. Moreover, we identified that vascular endothelial growth factor A (VEGFA) was a target gene of miR-195-5p, which could negatively regulate VEGFA expression in vitro. Inhibitors of miR-195-5p subsequently contributed to renal injury, which was reversed by VEGFA loss. In conclusion, miR-195-5p may repress AKI by targeting VEGFA.

Renoprotective effect and mechanism of polysaccharide from Polyporus umbellatus sclerotia on renal fibrosis.

As a fungal polysaccharide, polysaccharide (PPUS) from Polyporus umbellatus sclerotia have showed remarkable anti-inflammatory activities. In view of the closely relationship between inflammation and renal fibrosis, and considering the significant role of other fungal polysaccharides on treatment of renal fibrosis, we speculated that PPUS may have therapeutic effects on renal fibrosis. However, there was not any reports about PPUS treatment this disease. The purpose of this paper is to investigate renoprotective effect and mechanism of PPUS on renal fibrosis. The results indicated that PPUS can improve renal function and ameliorate the degree of renal collagen deposition and further fibrosis. Its mechanism was found to be related with decreased inflammation, suppressive epithelial-mesenchymal transition, reconstructed the balance of matrix metalloproteinases and tissue inhibitor of metalloproteinases, and pro-fibrotic and anti-fibrotic factors. The data implied that PPUS can serve as a clinical candidate on treatment of renal interstitial fibrosis.

The Evolution of Metastatic Colorectal Cancer Clinical Trials: Application of the ASCO Framework for Assessing Value.

Background: Phase III trials in metastatic colorectal cancer (mCRC) have collectively led to progressive advancements in patient outcomes over the past decades. This study characterizes the evolution of mCRC phase III trials through assessing the value of cancer therapy, as measured by the ASCO Value Framework. Methods: Phase III trial results of systemic therapy for mCRC published between 1980 and 2015 were identified, and their outcome, statistical significance, journal impact factor, and citation by the 2016 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CRC were recorded. For each trial, the net health benefit (NHB) score was calculated using the June 2015 (original) and May 2016 (revised) ASCO Value Framework: Advanced Disease. Results: There were 114 mCRC phase III trials eligible for calculation of the NHB score. Using the revised framework, the median NHB score was 4.6 (range, -30 to 43.5); 12% of trials received bonus points. Trials with statistically significant results had higher NHB scores compared with nonsignificant trials (median NHB score, 21.6 vs 2.9; P<.0001). Clinical trials cited in the NCCN Guidelines had higher NHB scores than those not cited (median score, 8.0 vs 0.3; P=.02). In multivariate linear regression analysis, the only significant predictor of high NHB score was statistically significant studies. Conclusions: The median NHB score for mCRC phase III trials was 4.6. Higher NHB scores are associated with statistically significant studies and are cited in the NCCN Guidelines, a surrogate for practice-changing trials. The 2016 ASCO Value Framework may not fully capture the benefits on an individual patient level.

Locating sex- and gender-specific data in health promotion research: evaluating the sensitivity and precision of published filters.

OBJECTIVE: This study explored the effectiveness of search filters in identifying sex- and gender-specific data in health promotion studies that are indexed in MEDLINE. METHODS: Literature searches were conducted to identify studies on patient or consumer attitudes and behaviors toward colorectal cancer screening, nutritional labeling, and influenza vaccination. Publications reporting sex- or gender-specific outcome data constituted the gold standards for this study. The sensitivity and precision of previously published gender-specific filters, as well as individual filter component terms, were calculated and compared with values identified in prior studies. RESULTS: The sensitivity and precision of published sex or gender filters varied across topics. Sensitivity values ranged from 14.3% to 92.5%, while precision varied from 17.9% to 51.4%. These filters were less sensitive and less precise in their identification of relevant studies than has been reported in previous studies. Further, while the MEDLINE Medical Subject Headings (MeSH) term "Sex Factors" achieved the greatest average precision (59.3%) of any individual filter term, the MEDLINE check tag "Female" returned the highest average sensitivity (90.1%), with an average precision of 25.0% across topics. CONCLUSIONS: Although search filters can facilitate the identification of research evidence to enable decision making, variability in study abstracting and indexing can limit the generalizability and usability of these filters. This potential for variability should be considered when deciding to incorporate a search filter into any literature search. This research highlights the importance of this awareness when developing strategies for searching the published literature and the potential value of supplementing database searching with other methods of study identification.

Berberine nanoparticles protects tubular epithelial cells from renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (I/R) injury is one of the most common causes of acute renal failure, the prognosis of which remains poor and there still lacks of effective therapeutics available in the clinic. This study aimed at investigating the effects of Berberine nanoparticles (BBR-NP) on the ischemia-reperfusion injury of renal tubular epithelial cells and underlying the mechanisms. Our results showed that in a rat model of renal I/R injury, BBR and BBR-NP protected renal against injury both functionally (as assessed by serum urea nitrogen and creatinine level) and morphologically (as assessed by HE staining, transmission electron microscopy and TUNEL staining) in a dose-dependent manner, with the effects of BBR-NP superior to BBR alone. Mechanism investigation showed that BBR-NP reversed oxidative stress and subsequent apoptosis of renal cells, as demonstrated by the decreased expression of proteins involved in the oxidative stress and mitochondrial stress pathways. In conclusion, our study showed that BBR-NP is superior to BBR alone in protecting renal against I/R injury and explored the underlying mechanisms, which should be tested in further studies and might give impetus to the development of novel therapeutics based on BBR-NP against renal I/R.

Side Effects Associated with the Use of Intensity-Modulated Radiation Therapy in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of the study was to establish the efficacy and safety of breast intensity-modulated radiation therapy (IMRT) compared with non-IMRT standard wedge radiation therapy (RT) for the treatment of adjuvant breast cancer. METHODS: A systematic review and meta-analysis were completed using STATA and a random effects model. A total of 1,499 citations were identified from the literature search. Of those, 1,475 were excluded based on abstract review. Full texts of 24 remaining articles were reviewed and 11 articles were included in the final analysis. Side effects were analysed as the primary outcomes of interest. We calculated individual odds ratios and 95% confidence intervals for 17 classifications of side effects reported. The data for eight classifications of side effects were then pooled for meta-analyses to obtain more precise estimates of the relationships between adjuvant RT and a particular side effect. RESULTS: The pooled analyses revealed potential protective associations between adjuvant IMRT and two acute side effects: dermatitis and moist desquamation. The remaining pooled estimates suggest that the odds of developing edema, hyperpigmentation, fat necrosis, pain, induration were no worse, nor better among those treated with IMRT compared with those treated with non-IMRT standard wedge RT. CONCLUSION: The pooled estimates from this meta-analysis are in line with the existing evidence. When the outcome of interest is reduction of the acute side effects: dermatitis and moist desquamation IMRT is a viable treatment option for women undergoing external beam RT after breast-conserving surgery.

Making literature reviews more ethical: a researcher and health sciences librarian collaborative process.

BACKGROUND: With emphasis on evidence-based medical care, 'evidence' is often the result of literature reviews. Hence, the critical question, "are literature reviews comprehensive?" AIM: This study compares the literature generated by a researcher and a health sciences librarian (HSL). METHODS: The Research Associate and the HSL conducted a parallel, segregated literature search on 'patient-centered care'. RESULTS: The Research Associate identified 215 manuscripts, and the HSL 129 manuscripts. Overlap was only 55 manuscripts. Differences in process and blind spots are discussed. CONCLUSION: To improve the quality of research outcomes, it seems prudent and ethical to have a synergistic collaboration between researchers and HSLs. Given that this is just one case study that has looked into the issue, further research is strongly encouraged.

Meta-analytic comparison of randomized and nonrandomized studies of breast cancer surgery.

BACKGROUND: Randomized controlled trials (RCTs) are thought to provide the most accurate estimation of "true" treatment effect. The relative quality of effect estimates derived from nonrandomized studies (nRCTs) remains unclear, particularly in surgery, where the obstacles to performing high-quality RCTs are compounded. We performed a meta-analysis of effect estimates of RCTs comparing surgical procedures for breast cancer relative to those of corresponding nRCTs. METHODS: English-language RCTs of breast cancer treatment in human patients published from 2003 to 2008 were identified in MEDLINE, EMBASE and Cochrane databases. We identified nRCTs using the National Library of Medicine's "related articles" function and reference lists. Two reviewers conducted all steps of study selection. We included studies comparing 2 surgical arms for the treatment of breast cancer. Information on treatment efficacy estimates, expressed as relative risk (RR) for outcomes of interest in both the RCTs and nRCTs was extracted. RESULTS: We identified 12 RCTs representing 10 topic/outcome combinations with comparable nRCTs. On visual inspection, 4 of 10 outcomes showed substantial differences in summary RR. The pooled RR estimates for RCTs versus nRCTs differed more than 2-fold in 2 of 10 outcomes and failed to demonstrate consistency of statistical differences in 3 of 10 cases. A statistically significant difference, as assessed by the z score, was not detected for any of the outcomes. CONCLUSION: Randomized controlled trials comparing surgical procedures for breast cancer may demonstrate clinically relevant differences in effect estimates in 20%-40% of cases relative to those generated by nRCTs, depending on which metric is used.