Myrtenol improves brain damage and promotes angiogenesis in rats with cerebral infarction by activating the ERK1/2 signalling pathway.

CONTEXT: Cerebral ischaemia/reperfusion (I/R) injury has a high disability and fatality worldwide. Myrtenol has protective effects on myocardial I/R injury through antioxidant and anti-apoptotic effects. OBJECTIVE: This study investigated the effect of myrtenol on cerebral ischaemia/reperfusion (I/R) injury and the underlying mechanism. MATERIALS AND METHODS: Cerebral I/R injury was induced in adult Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 90 min. MCAO rats were treated with or without myrtenol (10, 30, or 50 mg/kg/day) or/and U0126 (10 µL) intraperitoneally for 7 days. RESULTS: In the present study, myrtenol had no toxicity at concentrations up to 1.3 g/kg. Myrtenol treatment improved neurological function of MCAO rats, with significantly (p < 0.05) improved neurological deficits (4.31 ± 1.29 vs. 0.00) and reduced brain edoema (78.95 ± 2.27% vs. 85.48 ± 1.24%). Myrtenol extenuated brain tissue injury and neuronal apoptosis, with increased Bcl-2 expression (0.48-fold) and decreased Bax expression (2.02-fold) and caspase-3 activity (1.36-fold). Myrtenol promoted angiogenesis in the brain tissues of MCAO rats, which was reflected by increased VEGF (0.86-fold) and FGF2 (0.51-fold). Myrtenol promoted the phosphorylation of MEK1/2 (0.80-fold) and ERK1/2 (0.97-fold) in MCAO rats. U0126, the inhibitor of ERK1/2 pathway, reversed the protective effects of myrtenol on brain tissue damage and angiogenesis in MCAO rats. DISCUSSION AND CONCLUSIONS: Myrtenol reduced brain damage and angiogenesis through activating the ERK1/2 signalling pathway, which may provide a novel alternative strategy for preventing cerebral I/R injury. Further in vitro work detailing its mechanism-of-action for improving ischaemic cerebral infarction is needed.

Downregulated FOXO3a Associates With Poor Prognosis and Promotes Cell Invasion and Migration via WNT/ß-catenin Signaling in Cervical Carcinoma.

Background: Emerging studies have demonstrated that the Forkhead transcription factor FOXO3a is closely correlated with the progression of multiple tumors. Nevertheless, the biological role and prognostic value of FOXO3a have yet to be fully elucidated in cervical carcinoma. This study was designed to determine the molecular mechanism and prognosis of FOXO3a in cervical carcinoma. Methods: The protein levels of FOXO3a were detected using immunohistochemistry and Western blotting. The relationships between FOXO3a expression and clinicopathological variables were analyzed. The biological mechanism of FOXO3a in cervical carcinoma cells (HeLa and CaSki) was investigated. We also explored the effect of FOXO3a on WNT/ß-catenin signaling with respect to its expression and function. Results: The results demonstrated that decreased FOXO3a expression was related to increased tumor stage and grade, positive lymph node metastasis, and poor survival outcome in cervical carcinoma. Survival analysis revealed that the FOXO3a level is an independent prognostic factor for cervical carcinoma patients. Furthermore, the data indicated that the downregulation of FOXO3a expression promotes cell invasion and migration, while FOXO3a overexpression exhibited the opposite effects on cervical carcinoma. In addition, FOXO3a acted as a negative regulator of the canonical WNT/ ß-catenin pathway in cervical carcinoma. Moreover, overexpression of FOXO3a also inhibited the expression of MMP2 and MMP9. Conclusion: These results reveal that FOXO3a, serving as a tumor suppressor gene, could suppress cell invasion and migration via the WNT/ß-catenin signaling pathway and indicates a good prognosis in cervical carcinoma.

Combined Snail and E-cadherin Predicts Overall Survival of Cervical Carcinoma Patients: Comparison Among Various Epithelial-Mesenchymal Transition Proteins.

BACKGROUND: Activation of Snail and synergistic loss of E-cadherin are hallmark features of the epithelial-mesenchymal transition (EMT), which contributes to the metastasis phenotype of epithelial cancer cells. However, the prognostic impact of Snail and of its combination with E-cadherin and with other EMT prognostic markers has not yet been systematically studied in cervical carcinoma. This study aimed to explore the prognostic value of combined Snail and E-cadherin in patients with cervical carcinoma and compared it to the prognostic value of other EMT prognostic markers. METHODS: We retrospectively identified every initial diagnosis of cervical carcinoma among 203 patients treated at our hospital in China from January 2008 to March 2013. We examined the prognostic significance of Snail and other EMT protein markers, such as E-cadherin, Slug, ZEB1, Twist, Vimentin, and Survivin, by univariate and multivariate survival analyses. RESULTS: Multivariate analyses showed that Snail and E-cadherin were significant biomarkers for overall survival (OS) in cervical carcinoma patients (HR, hazard ratio = 1.744, P = 0.036 and HR = 1.738, P = 0.047; respectively). Moreover, a combined index including Snail and E-cadherin showed enhanced prognostic value compared to that of Snail or E-cadherin alone. The present data demonstrate that Snail shows a negative correlation with E-cadherin (P < 0.001). High Snail expression and low E-cadherin expression were also more common in high tumor stages (P = 0.044 and P = 0.036; respectively), and lymph node metastasis (both P < 0.001). Moreover, Snail was a superior prognosis factor compared to Slug, ZEB1, Twist, Vimentin, and Survivin in cervical carcinoma. CONCLUSION: Based on our results, Snail and E-cadherin may be considered as independent prognosis markers, and the combination of Snail and E-cadherin might improve the OS prediction accuracy for patients with cervical carcinoma.

The Prognostic Value of Homocysteine in Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Background: This comprehensive meta-analysis aimed to assess whether an increased homocysteine (Hcy) level is an independent predictor of unfavorable outcomes in acute ischemic stroke (AIS) patients. Methods: A comprehensive literature search was conducted up to August 1, 2020 to collect studies reporting Hcy levels in AIS patients. We analyzed all the data using Review Manager 5.3 software. Results: Seventeen studies with 15,636 AIS patients were selected for evaluation. A higher Hcy level was associated with a poorer survival outcome (OR 1.43, 95% CI: 1.25-1.63). Compared with the AIS group, Hcy levels were significantly lower in the healthy control patients, with an SMD of 5.11 and 95% CI (1.87-8.35). Analysis of the different subgroups of AIS demonstrated significant associations between high Hcy levels and survival outcomes only in Caucasian and Asian patients. Moreover, whereas high Hcy levels were closely associated with gender, B12 deficiency, smoking, and patients who received tissue plasminogen activator treatment, no significant difference was found between increased Hcy levels and age, drinking, hypertension, diabetes mellitus, and hyperlipidemia. In addition, the cut-off value (20.0 µmol/L) might be an optimum cut-off index for AIS patients in clinical practice. Conclusion: This meta-analysis reveals that the Hcy level may serve as an independent predictor for unfavorable survival outcomes in AIS patients, particularly in Caucasian and Asian AIS patients. Further studies can be conducted to clarify this relationship.

Physical therapy in the management of stone fragments: progress, status, and needs.

With an increased risk of symptomatic events, the complications related to residual fragments are complex and intractable. The management of stone fragments is a challenge to urologists. This review focused on the progress, status, and needs of the newly developed physical therapies to remove fragments and improve the stone-free rate. Physical therapies, including mechanical percussion, diuresis, and inversion therapy, ultrasonic propulsion technology, glue-clot technology, and magnetization technology, will facilitate progress in endoscopic stone fragment retrieval.

Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis.

Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy.

A Phenylselenium-Substituted BODIPY Fluorescent Turn-off Probe for Fluorescence Imaging of Hydrogen Sulfide in Living Cells.

Herein a phenylselenium-substituted BODIPY (1) fluorescent turn-off sensor was developed for the purpose to achieve excellent selectivity and sensitivity for H2S detection based on the substitution reaction of the phenylselenide group at the 3-position with H2S. The excess addition of hydrogen sulfide promoted further substitution of the phenylselenide group at the 5-position of the probe and was accompanied by a further decrease in fluorescence emission intensity. Sensor 1 demonstrated remarkable performance with 49-fold red color fluorescence intensity decrease at longer excitation wavelength, a low detection limit (0.0025 µM), and specific fluorescent response toward H2S over anions, biothiols, and other amino acids in neutral media. It showed no obvious cell toxicity and good membrane permeability, which was well exploited for intracellular H2S detection and imaging through fluorescence microscopy imaging.

Clinicopathological and Prognostic Value of Ki-67 Expression in Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Ki-67 is an established marker of cell proliferation, and the Ki-67 index correlates with the clinical course of several cancer types, including bladder cancer (BC). However, the clinicopathological and prognostic significance of Ki-67 in bladder cancer remains unclear. Therefore, we performed a systematic review and meta-analysis to clarify this relationship. METHODS: A comprehensive literature search for relevant studies published up to February 1, 2016, was performed using PubMed, Cochrane Library, Embase and ISI Web of Knowledge. The effects of Ki-67 expression on survival outcome in patients with BC and BC subtypes were evaluated. Furthermore, the relationship between Ki-67 expression and the clinicopathological features of BC were assessed. RESULTS: Thirty-one studies with 5147 bladder cancer patients were selected for evaluation. Ki-67 expression was significantly associated with shorter recurrence-free (HR 1.69, 95% CI: 1.33-2.14), progression-free (HR 1.89, 95% CI: 1.43-2.51), overall (HR 2.03, 95% CI: 1.31-3.16), and cancer-specific (HR 1.69, 95% CI: 1.47-1.95) survival. Moreover, whereas high expression was more common in high tumor stage, recurrence status, tumor size, there was no correlation between high Ki-67 expression and age, gender, smoking habits, and tumor number. Importantly, analysis of the different subgroups of BC suggested that significant correlations between high Ki-67 expression and survival outcome (recurrence-free/progression-free/overall/cancer-specific survival) are present only in European-American patients. CONCLUSION: The present results indicate that over-expression of Ki-67 is distinctly correlated with poor patient survival. Ki-67 may serve as a valuable biomarker for prognosis in BC patients, particularly in non-Asian BC patients. The results suggest no significant association between Ki-67 expression and BC prognosis in Asian patients. Further efforts are needed to fully clarify this relationship.

Clinical and prognostic value of preoperative hydronephrosis in upper tract urothelial carcinoma: a systematic review and meta-analysis.

Background. Epidemiological studies have reported various results relating preoperative hydronephrosis to upper tract urothelial carcinoma (UTUC). However, the clinical significance and prognostic value of preoperative hydronephrosis in UTUC remains controversial. The aim of this study was to provide a comprehensive meta-analysis of the extent of the possible association between preoperative hydronephrosis and the risk of UTUC. Methods. We searched PubMed, ISI Web of Knowledge, and Embase to identify eligible studies written in English. Summary odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Results. Nineteen relevant studies, which had a total of 5,782 UTUC patients enrolled, were selected for statistical analysis. The clinicopathological and prognostic relevance of preoperative hydronephrosis was evaluated in the UTUC patients. The results showed that all tumor stages, lymph node status and tumor location, as well as the risk of cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were significantly different between UTUC patients with elevated preoperative hydronephrosis and those with low preoperative hydronephrosis. High preoperative hydronephrosis indicated a poor prognosis. Additionally, significant correlations between preoperative hydronephrosis and tumor grade (high grade vs. low grade) were observed in UTUC patients; however, no significant difference was observed for tumor grading (G1 vs. G2 + G3 and G1 + G2 vs. G3). In contrast, no such correlations were evident for recurrence status or gender in UTUC patients. Conclusions. The results of this meta-analysis suggest that preoperative hydronephrosis is associated with increased risk and poor survival in UTUC patients. The presence of preoperative hydronephrosis plays an important role in the carcinogenesis and prognosis of UTUC.

A fluorescence enhancement probe based on BODIPY for the discrimination of cysteine from homocysteine and glutathione.

Herein, a fluorescent probe BODIPY-based glyoxal hydrazone (BODIPY-GH) (1) for cysteine based on inhibiting of intramolecular charge transfer (ICT) quenching process upon reaction with the unsaturated aldehyde has been synthesized, which exhibits longer excitation wavelength, selective and sensitive colorimetric and fluorimetric response toward cysteine in natural media. The probe shows highly selectivity towards cysteine over homocysteine and glutathione as well as other amino acids with a significant fluorescence enhancement response within 15min In the presence of 50 equiv. of homocysteine, the emission increased slightly within 15min and completed in 2.5h to reach its maximum intensity. Therefore, the discrimination of cysteine from homocysteine and glutathione can be achieved through detection of probe 1. It shows low cytotoxicity and excellent membrane permeability toward living cells, which was successfully applied to detect and image intracellular cysteine effectively by confocal fluorescence imaging.

[Updated roles of SIRT1 in prostate diseases].

Silent information regulator 1(SIRT1),an NAD+dependent class-III histone deacetylase,is implicated in diverse cellular processes. SIRT1 has been reported as a key regulator of metabolism,oxidative stress,and cell survival,proliferation,apoptosis and autophagy. It also plays an important role in a variety of physiological processes and health conditions,including aging,inflammation,metabolic disease,tumor,cardiovascular disease,and neurodegeneration. In recent years,the incidence of prostate diseases is increasing,but the therapeutic options are relatively limited. The importance of SIRT1 in prostate diseases has become increasingly apparent,and more rational application of sirtuin inhibitors or activators is shedding new light on the management of prostate diseases.This review focuses on the role of SIRT1 in prostate diseases and introduces some novel strategies for their diagnosis and treatment.