Preoperative positive voided urine cytology predicts poor clinical outcomes in patients with upper tract urothelial carcinoma undergoing nephroureterectomy.

BACKGROUND: Performance of urinary cytology is recommended as the part of a standard diagnostic workup and base surveillance regimens in upper tract urothelial carcinoma (UTUC). However, the effect of positive voided urine cytology (VUC) on UTUC prognosis, compared with negative VUC, has not been fully demonstrated. This study aimed to evaluate the impact of preoperative VUC on predicting intravesical recurrence, disease recurrence, and mortality in patients with UTUC who underwent nephroureterectomy (RNU). METHODS: Clinicopathological information was collected from 315 UTUC patients treated with RNU. The association between VUC and oncological outcomes was analyzed using the Kaplan-Meier method with log-rank test and Cox proportional hazards regression models. Multiple logistic regression analysis was performed to identify the influence of VUC on tumor grade. RESULTS: Preoperative positive VUC, presenting in 101 patients (32%), was significantly associated with tumor multifocality (P = 0.017) and higher tumor grade (P = 0.010). On multivariable Cox regression analyses, preoperative positive VUC was an independent prognostic factor of intravesical recurrence-free survival (RFS) (hazard ratio [HR] = 2.21, 95% confidence interval [CI] 1.06-4.64; P = 0.035), RFS (HR = 1.80, 95% CI 1.08-2.99; P = 0.023), and cancer-specific survival (CSS) (HR = 1.87, 95% CI 1.10-3.18; P = 0.020), but not overall survival (HR = 1.32, 95% CI 0.80-2.18; P = 0.28). Logistic regression analysis revealed that VUC was related to high tumor grade in UTUC (odds ratio = 2.23, 95%CI 1.15-4.52). CONCLUSION: Preoperative positive VUC significantly increases the risk of intravesical recurrence in UTUC patients undergoing RNU. In addition, positive VUC is an adverse predictor of RFS and CSS, which might be due to the association between positive VUC and high tumor grade.

Novel antioxidants' synthesis and their anti-oxidative activity through activating Nrf2 signaling pathway.

Novel structure compounds (WS) containing 3,4,5-trimethoxyphenyl and acyl pyrazole were designed and synthesized based combination principles. Among them, WS13 was screened out to possess desirable anti-oxidative activity in vitro. Cell survival assay and apoptosis experiment in H2O2 induced PC12 cells injury model all showed that its cytoprotection exhibited a concentration-effect manner. WS13 at 10µM could remove ROS with equal effiency to edaravone. Further, it clearly activated Nrf2 nuclear translocation and upregulated GCLC mRNA transcription and protein expression in dose-dependent manner, and its cytoprotection was reversed by GCLC protein inhibitor. In total, WS13 with further promotion can serve as Nrf2-GCLC activator in anti-oxidative therapy.

MiR429 expression level in renal cell cancer and its correlation with the prognosis of patients.

PURPOSE: To test the hypothesis that miR429 expression in renal cancer patients is increased and plays a role in the pathogenesis of the disease. METHODS: Twenty-seven renal cancer patients admitted to our hospital from May 2014 to May 2015 were enrolled as the study group, and 28 non-cancer patients were selected during the same period as the control group. Renal biopsy and serum samples were used to detect miR429 expression levels, and the patient histories were obtained to make relevant associations to clinical outcomes. In addition, the renal cancer cell line SK458 was used for overexpressing or knocking out miR429 in in vitro experiments to observe changes in proliferation and apoptosis rates. RESULTS: The expression levels of miR429 in renal tissues and serum of renal cancer patients were significantly higher compared with control patients (p<0.05). In addition, a correlation was found between the levels of miR429 in the serum of renal cell cancer patients and their clinical outcome after conventional treatment, with patients expressing lower miR429 levels showing better clinical outcomes. Finally, experiments with renal cancer cells revealed that the proliferation of cells overexpressing miR429 was increased and their apoptosis rate was significantly reduced, while the opposite was true in miR429-knockout cells. CONCLUSIONS: It seems that miR429 can inhibit normal apoptosis rates and lead to high proliferation rates. Accordingly, the higher serum miR429 level in renal cancer patients suggests that it plays a role in the pathogenesis of the disease, while the differential miR429 levels according to the patients' clinical outcomes after treatment suggest that miR429 may be useful as a marker for prognosis.

W346 inhibits cell growth, invasion, induces cycle arrest and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway.

The therapeutic agent selectively killing cancer cells is urgently needed for gastric cancer treatment. Curcumin has been investigated for its effect on the cancer treatment because of its significant therapeutic potential and safety profile. A synthetic unsymmetry mono-carbonyl compound termed W346 was developed from curcumin. In this study, we investigated the potential antineoplastic effect and mechanism of W346 against human gastric cancer cells. W346 suppressed the proliferation and invasion, blocked cell cycle arrest at G2/M phase, and increased apoptosis in gastric cancer cells, and it presented obviously improved anticancer activity than curcumin. Moreover, W346 effectively inhibited tumor necrosis factor (TNF-α)-induced NF-κB activation by suppressing IKK phosphorylation, inhibiting IκB-α degradation, and restraining the accumulation of NF-κB subunit p65 nuclear translocation. W346 also affected NF-κB-regulated downstream products involved in cycle arrest and apoptosis. In a word, W346 exhibited significantly improved anti-gastric cancer activity over curcumin by targeting NF-κB signaling pathway, and it is likely to be a promising starting point for the development of curcumin-based therapeutic agent.

Synthetic chalcones with potent antioxidant ability on H2O2-induced apoptosis in PC12 cells.

Chalcone derivatives (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one (Compounds 1 and 2) have been demonstrated to be potent anti-inflammatory agents in our previous study. In light of the relationship of intracellular mechanisms between anti-inflammatories and antioxidants, we further designed and synthesized a series of chalcone derivatives based on 1 and 2, to explore their antioxidant efficacy. The majority of the derivatives exhibited strong protective effects on PC12 (PC12 rat pheochromocytoma) cells exposed to H2O2, and all compounds were nontoxic. A preliminary structure-activity relationship was proposed. Compounds 1 and 1d ((E)-2-methoxy-4-(3-(4-methoxyphenyl)-3-oxoprop-1-en-1-yl) phenyl acrylate) exerted the action in a good dose-dependent manner. Quantitative RT-PCR (qRT-PCR) and western blot analysis showed that 1 and 1d significantly improve the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant genes g-Glutamylcysteine Ligase Catalytic Subunit (GCLC) and heme oxygenase-1 (HO-1) and their corresponding proteins (γ-glutamyl cysteine synthase (γ-GCS) and HO-1) in PC12 cells. Inhibition of GCLC and HO-1 by specific inhibitors, L-buthionine-S-sulfoximine (BSO) and zinc protoporphyrin (ZnPP), respectively, partially reduce the protective effect of 1 and 1d. These data present a series of novel chalcone analogs, especially compounds 1 and 1d, as candidates for treating oxidative stress-related disease by activating the Nrf2-antioxidant responsive element (ARE) pathway.

Colorectal Cancer Stem Cells and Targeted Agents.

Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies.

Prognostic value of the sarcomatoid component in bladder cancer: A propensity score matching study.

Sarcomatoid carcinoma of the bladder is rare, and little is known about the prognostic impact of the proportion of sarcomatoid components of the bladder. The present study aimed to assess the prognostic value of the proportion of sarcomatoid components with regard to death and recurrence rates in patients with bladder cancer (BC), and to validate the worse survival results of sarcomatoid carcinomas of the bladder using propensity score matching. Patients with sarcomatoid carcinoma of the bladder who were treated at the Affiliated Hospital of Qingdao University between August 2010 and May 2021 were included in the study. A 1:2 propensity score matching system based on age, sex and pathological T stage was used for sarcomatoid and non-sarcomatoid carcinoma matching. Finally, 114 patients with BC were included. Patients with sarcomatoid carcinoma had worse 5-year cancer-specific survival (CSS) (69.1 vs. 86.9%; log-rank P=0.008) and recurrence-free survival (RFS) (64.1 vs. 83.6%; log-rank P=0.001) rates compared with patients with non-sarcomatoid carcinoma, as had the subgroup with muscle invasion. Multivariate analysis revealed sarcomatoid carcinoma as an independent prognostic factor. Patients with a low proportion of sarcomatoid components (1-50%) had a better prognosis than patients with a high proportion (>50%), and no significant difference was found compared with the non-sarcomatoid group. Overall, a proportion of sarcomatoid components >50% was a predictor of CSS and RFS. Sarcomatoid components markedly increased the risk of death and recurrence in muscle-invasive BC, but not in non-muscle-invasive BC. A higher proportion of sarcomatoid components was significantly associated with poorer survival.

The NOAA NCEI marine microplastics database.

Microplastics (<5 mm) pollution is a growing problem affecting coastal communities, marine ecosystems, aquatic life, and human health. The widespread occurrence of marine microplastics, and the need to curb its threats, require expansive, and continuous monitoring. While microplastic research has increased in recent years and generated significant volumes of data, there is a lack of a robust, open access, and long-term aggregation of this data. The National Oceanic and Atmospheric Administration (NOAA) National Centers for Environmental Information (NCEI) now provides a global open access to marine microplastics data on an easily discoverable and accessible GIS web map and data portal ( https://www.ncei.noaa.gov/products/microplastics ). The objective of this data portal is to develop a repository where microplastics data are aggregated, archived, and served in a user friendly, consistent, and reliable manner. This work contributes to NCEI's efforts towards data standardization, integration, harmonization, and interoperability among national and international collaborators for monitoring global marine microplastics. This paper describes the NOAA NCEI global marine microplastics database, its creation, quality control procedures, and future directions.

Effects of Sports Public Goods on the Health of the Elderly: Empirical Evidence from China.

Sports public service can promote the elderly to participate in sport exercises and have a positive impact on health of the elderly. The aim of this study was to identify the effect of sport public service on the health and to study the meditation effect of physical activity. We conducted a questionnaire survey on sports public service and the health of the elderly in China, and established a mediation effect model to measure the impact of five categories of sports public service on the health of the elderly. The final sample comprised 1089 older adults (548 males and 541 females). Cronbach's α was over 0.7. Sport public service have positive effect on the health of the elderly, but they have meditation effect on both frequency and duration of physical exercise of the elderly. Among which the instruction of physical activity and service of sport exercises are the most significant factors. Sports public service for the elderly in China are not well balanced both in regions and among people, with more goods in towns and cities but less in rural areas. This study clarifies the impact of sports public service on the health of the elderly, and empirically analyses its meditation effect on physical exercise of the elderly. It is emphasized that the provision of sports public service in China is not to build sports facilities, but to provide more instruction and sports public services for residents physical exercise.

The effect of cyclodextrins on the ethanol tolerance of microorganisms suggests potential application.

Cyclodextrins (CDs) are used in food, pharmaceutical, and chemical industries, as well as agriculture and environmental engineering. Cyclodextrin glucanotransferase (CGTase) is an important industrial extracellular enzyme which is used to produce CDs and oligosaccharides. We previously developed a novel yeast-surface CGTase expression system which was used for the production of CDs from starch. In the present study, we showed that the presence of CDs may increase the ethanol tolerance of microorganisms. The cell numbers of Saccharomyces cerevisiae and Escherichia coli in the presence of ß-cyclodextrin and ethanol were 1,000-fold and 10-fold higher than that without CDs. The yeast strain with the immobilized CGTase produced 13 g CDs/l and 1.8 g ethanol/l when it was incubated in yeast medium supplemented with 4% starch. The effect of CDs on microorganisms suggests a potential application for the co-production of CDs and ethanol.

Endothelial progenitor cells are associated with plasma homocysteine in coronary artery disease.

OBJECTIVE: Little is known about the association between plasma homocysteine (Hcy) and endothelial progenitor cells (EPCs) in coronary artery disease (CAD). METHODS: Blood mononuclear cells were isolated from CAD (n = 30) patients and non-CAD controls (n = 30). Flow cytometric analysis and an in vitro culture system was used to evaluate the number and function of the EPC. Plasma homocysteine (Hcy) concentration was measured by an automated fluorescence polarization immunoassay. RESULTS: Hcy level was higher in CAD than in non-CAD (13.69 +/- 4.48 vs 9.34 + 2.31 pmol/L, P < 0.01). The number of circulating EPCs from CAD was decreased compared with non-CAD (58.7 +/- 10.6 vs. 94.3 +/- 15.1 cells/ml, P < 0.01). This decrease of EPCs in CAD was also detected (33.5 +/- 6.9 vs. 55.9 +/- 9.7 EPCs/x200 field; P < 0.01) in an in vitro culture system. The numbers of circulating and differentiated EPCs were both inversely correlated with Hcy. EPCs from CAD were significantly impaired in their migratory capacity and ability to adhere to fibronectin. CONCLUSIONS: We observed the correlation between Hcy level and EPC number, and also found an increased Hcy level in CAD patients. It will be interesting to reveal the underlying mechanisms contributing to the correlation and examine the possible causal relationship between Hcy levels and CAD.

(E)-1-(4-Meth-oxy-phen-yl)-3-(2,4,6-trimeth-oxy-phen-yl)prop-2-en-1-one.

In the title compound, C(19)H(20)O(5), the dihedral angle between the two aromatic rings is 18.23 (4)°. The crystal structure exhibits only weak C-H⋯π and C-H⋯O contacts between the mol-ecules.

Simvastatin prevents ERK activation in myocardial hypertrophy of spontaneously hypertensive rats.

BACKGROUND: Statins exert regression of left ventricular hypertrophy independent of their plasma cholesterol-lowering actions. However, the underlying mechanism is not clear. METHODS: We tested the hypothesis that the extracellular signal-regulated kinases (ERKs) signaling pathway could be a target of simvastatin (SIM) and involved in SIM-induced LVH regression in spontaneously hypertensive rats (SHR). Fourteen 14-week old-SHR males were randomly divided into a SHR SIM group (n = 7) or a SHR control group (n = 7). The SHR SIM group was given SIM 40 mg/kg · d via injection ig, while the SHR control group was routinely given only vehicle (0.5% carboxymethyl cellulose ig). Seven Wistar Kyoto rats served as normal controls. RESULTS: Ten weeks of treatment with SIM in SHR had no influence on blood pressure. The ratio of left ventricle weight to body weight in the SHR SIM group was decreased significantly compared to that in the SHR control group (p < 0.05). Among the three groups there was no significant difference in total ERK expression (p > 0.05). SIM treatment caused a significant reduction in the expression of phosphorylated-ERK, the kinase activity of ERK, the levels of mitogen-activated protein kinase phosphatase-1 protein and its mRNA (p <0.01 for all). CONCLUSIONS: The Hydroxymethylglutaryl coenzyme A reductase inhibitor SIM prevents the activation of ERK in SHR to mediate regression of myocardial hypertrophy in SHR.

Metabolically Abnormal Obesity Increases the Risk of Advanced Prostate Cancer in Chinese Patients Undergoing Radical Prostatectomy.

BACKGROUND: To investigate the pathological risk of prostate cancer (PCa) according to the obesity and metabolic status of Chinese patients undergoing radical prostatectomy. MATERIALS AND METHODS: We performed a retrospective cross-sectional study of 1016 patients with PCa who underwent radical prostatectomy and whose metabolic status and body mass index were examined. Multivariate logistic regression analysis was performed to examine the relationship between different metabolic obesity phenotypes and the pathological outcomes of PCa. RESULTS: Among 1016 men, 551 (54.2%), 106 (10.4%), 238 (23.4%), and 121 (11.9%) were assigned to the metabolically healthy and normal weight (MHNW) group, metabolically abnormal but normal weight (MANW) group, metabolically healthy but overweight or obese (MHO) group, and metabolically abnormal and overweight or obese (MAO) group, respectively. Compared with the MHNW group, the MAO group had a significantly greater risk of a higher prostatectomy Gleason score [odds ratio (OR), 1.907; 95% confidence interval (95% CI), 1.144-3.182], pathological stage (OR, 1.606; 95% CI, 1.035-2.493), and seminal vesicle invasion (OR, 1.673; 95% CI, 1.041-2.687). In contrast, the ORs were not increased in the MHO or MANW group. In the context of normal weight, metabolic disorders were associated with lymph node involvement. The metabolic status and body mass index were not associated with extracapsular extension or surgical margins in any of the four groups. CONCLUSION: The MAO phenotype is associated with aggressive PCa, including a higher prostatectomy Gleason score, pathological stage, and seminal vesicle invasion and might also be associated with disease progression. Obesity and metabolic disorders act synergistically to increase the pathological risk of PCa.

The inhibitory effects of soybean isoflavones on testicular cell apoptosis in mice with type 2 diabetes.

The aim of the study was to investigate the inhibitory effects of soybean isoflavones (SI) on testicular cell apoptosis in mice with type-2 diabetes, as well as any possible mechanisms of action. Thirty male C57BL/6J mice were randomly divided into the control, diabetic (model), and treatment (SI) groups (n=10 each). After treatment for 20 weeks, testicular cell apoptosis was detected and evaluated using DAPI staining. The expression and distribution of caspase-3 protein in testicular tissues was detected via immunohistochemistry, while caspase-3 mRNA expression was detected using RT-PCR. Bax and Bcl-2 protein expression was detected by western blot analysis. At week 20, DAPI staining showed that SI treatment significantly decreased testicular tissue cell apoptosis in diabetic mice. Immunohistochemical staining revealed that caspase-3 expression in the SI group was significantly reduced relative to the model group. RT-PCR showed that SI treatment significantly decreased caspase-3 mRNA expression relative to the model group. Western blot analysis revealed that SI treatment significantly decreased Bax protein expression and increased Bcl-2 protein expression (P<0.01). SI exhibited an inhibitory effect on testicular tissue cell apoptosis in mice with type 2 diabetes, with this effect possibly mediated by a decreased expression of caspase-3 and Bax and increased Bcl-2 protein expression.

A novel double carbonyl analog of curcumin induces the apoptosis of human lung cancer H460 cells via the activation of the endoplasmic reticulum stress signaling pathway.

Curcumin can inhibit the growth of a variety of cancer cells; however, its poor bioavailability and pharmacokinetic profiles, which are attributed to its instability under physiological conditions, have limited its application in anticancer therapy. In the present study, we screened a double carbonyl analog of curcumin (A17) and analyzed its effects and mechanism of inducing apoptosis in human lung cancer H460 cells. The results showed that A17 not only induced CHOP expression in human lung cancer H460 cells, but also induced the apoptosis of H460 cells in a dose-responsive manner, and this effect was related to corresponding activation of some important components in the endoplasmic reticulum (ER) stress-mediated apoptosis pathway. When CHOP was knocked down by specific siRNA, A17-induced cell apoptosis was attenuated, thereby further demonstrating that the apoptotic pathway is ER stress­dependent. Our studies demonstrated that A17 has better stability and antitumor activity than curcumin in H460 cells via an ER stress-mediated mechanism. These results imply that A17 could be further explored as a potential anticancer agent for the treatment of human non-small cell lung cancer (NSCLC).

[The diagnostic application of bedside measurement of plasma brain natriuretic in patients with heart failure].

OBJECTIVE: To investigate differential diagnoses value of ultra-rapid bedside measurement of brain natriuretic peptide (BNP) in patients with dyspnea. METHODS: Plasma BNP concentration were measured with immunofluorescence assay in 103 patients with dyspnea. Left ventricular ejection fraction (LVEF) and pulmonary capillary wedge pressure (PCWP) were determined by echocardiography and Swan-Ganz catheter in these patients on the same time, respectively. RESULTS: (1) Plasma BNP levels in the patients with heart failure were higher than those in the non-heart failure patients [(716 +/- 86 vs 46 +/- 7) ng/L, P < 0.01]. (2) The sensitivity, specificity and negative predictive values of Plasma BNP levels > or = 100 pg/ml for predicting heart failure were 95.2% (60/63), 93.0% (40/43) and 97.1% (100/103), respectively. (3) Plasma BNP levels were positively related to PCWP, and negatively related to LVEF (r = -0.56, both P < 0.01). CONCLUSION: Bedside BNP assay is sensitive and specific for diagnosing heart failure, and is useful in evaluating dyspnea in emergency care.

Yangxueqingnao particles inhibit rat vascular smooth muscle cell proliferation induced by lysophosphatidic acid.

OBJECTIVE: To observe the effect of Yangxueqingnao particles on rat vascular smooth muscle cell (VSMC) proliferation induced by lysophosphatidic acid (LPA). METHODS: The amount of (3)H-TdR ((3)H-thymidine) admixed in cultured rat VSMC was measured and mitogen-activated protein kinase (MAPK) activity and lipid peroxidation end product malondialdehyde (MDA) content of the VSMC were assayed. RESULTS: 1x10(-9), 1x10(-8), 1x10(-7) mol/L LPA in a concentration dependent manner, induced the amount of (3)H-TdR admixed, MAP kinase activity, and MDA content of the cultured rat VSMC to increase. However, 5%, 10%, and 15% Yangxueqingnao serum preincubation resulted in a decrease of 23.0%, 42.0%, and 52.0% (P<0.01) respectively in the amount of (3)H-TdR admixed, a decline in VSMC MAP kinase activity of 13.9% (P<0.05), 29.6% (P<0.01), and 48.9% (P<0.01) respectively, and also, a decrease in MDA content of VSMC of 19.4%, 24.7%, and 43.2% (P<0.01) respectively, in the 1x10(-7) mol/L LPA-treated VSMC. CONCLUSIONS: LPA activates the proliferation and lipid peroxidation of VSMC in a concentration dependent manner. The LPA-induced VSMC proliferation is related to the activity of MAP kinases, enzymes involved in an intracellular signalling pathway. The results of the present study showed that Yangxueqingnao particles can effectively inhibit LPA-induced VSMC proliferation, MAP kinase activation, and reduce lipid peroxidative lesion.