Synergetic effect of poly (ADP-ribosyl) polymerase (PARP) inhibitor and cisplatin on ovarian cancer

Purpose: To investigate the effect of the combination of poly (ADP-ribosyl) polymerase (PARP) inhibitor, talazoparib (BMN673), and cisplatin on the proliferation and apoptosis of ovarian cancer cells in vitro, and on xenograft tumors of ovarian cancer cells in vivo. Methods: Cell viability was determined by CCK-8 assay, while cell proliferation and cell cycle were assessed using colony formation assay and flow cytometry, respectively. Cell apoptosis was evaluated by flow cytometry and TUNEL assays. Western blot assay was used to measure the expression levels of proliferation- and apoptosis-related proteins. Results: The PARP inhibitor, BMN673, produced a dose-dependent synergistic effect with cisplatin (p < 0.05). Compared with when cisplatin or BMN673 was used alone, the combination of cisplatin and BMN673 significantly inhibited the growth of transplanted tumors (p < 0.05). Immunohistochemical analysis showed that cisplatin and BMN673 treatment increased the number of cells positive for TUNEL, but reduced the population of cells positive for Ki67. Conclusion: Thus, BMN673 and cisplatin are synergistic against ovarian cancer cells, and therefore, should be subjected to further investigations, including clinical trials, to determine the potentials of the combination for the management of ovarian carcinoma. Keywords: PARP inhibitor; Ovarian cancer; Xenografted tumor; Cisplati

Histological features of the gastric mucosa in children with primary bile reflux gastritis

<p>Abstract</p> <p>Background</p> <p>Bile reflux is one of the primary factors involved in the pathogenesis of gastric mucosal lesions in patients with chronic gastritis; however, little is known about the exact histological features of bile reflux and its contributions to gastric mucosal lesions in this disease, especially in children with primary bile reflux gastritis (BRG). The aim of this study was to investigate the classic histological changes of the gastric mucosa in children with primary BRG.</p> <p>Methods</p> <p>The Bilitec 2000 was used for 24 h monitoring of gastric bile in 59 children with upper gastrointestinal symptoms. The histological characteristics of the gastric mucosa were examined and scored.</p> <p>Results</p> <p>Thirteen of the 59 patients had a helicobacter pylori infection and were excluded; therefore, 46 cases were included in this study. The positive rate of pathological duodenogastric reflux was significantly higher in patients with foveolar hyperplasia than those without foveolar hyperplasia; however, the rate was significantly lower in patients with vascular congestion than those without vascular congestion. The longest reflux time and the total percentage time of bile reflux were significantly lower in patients with vascular congestion than those without vascular congestion. A total of 9 types of histological changes were analyzed using a binary logistic regression. Foveolar hyperplasia and vascular congestion in the superficial layer became significant variables in the last step of the stepwise regression.</p> <p>Conclusions</p> <p>Foveolar hyperplasia was associated with the severity of bile reflux, suggesting that it is a histological feature of primary BRG in children, while vascular congestion may be a protective factor.</p

Expression and Clinical Relevance of uPA and ET-1 in Non-small Cell Lung Cancer

Background and objective uPA and ET-1 proteins have been reported to be up-regulated in some of human cancers. The aim of this study is to investigate the alteration and clinical relevance of uPA and ET-1 protein levels in non-small cell lung cancer (NSCLC). Methods Expressions of uPA and ET-1 protein were detected in 155 cases of NSCLC with tissue microarrays and immunohistochemistry (TMA-IHC) technique. The correlations between the alteration of the two proteins and clinicopathological parameters were analyzed. Results Negative/weak, moderate and high expression of uPA were observed in 12.3%, 64.4% and 23.3% of squamous cell carcinomas, in 12.2%, 53.7% and 34.1% of adenocarcinomas, and in 12.3%, 58.7% and 29.0% of all cases. ET-1 presented negative/weak, moderate and high expression in 2.7%, 42.5% and 54.8% of squamous cell carcinomas, in 11.0%, 30.5% and 58.5% of adenocarcinomas, and in 7.1%, 36.1% and 56.8% of all cases. Simultaneously high expression of uPA and ET-1 were found in adenocarcinomas without lymph node metastasis (P=0.017). Adenocarcinoma patients with high expression of uPA or with high expression of both ET-1 and uPA had the longer survival time (P=0.007 and 0.016). Conclusion Detection of uPA and ET-1 protein levels might contribute to the prognosis evaluation of NSCLC

Ultralow phase noise microwave generation with an Er:fiber-based optical frequency divider

We present an optical frequency divider based on a 200 MHz repetition rate Er:fiber mode-locked laser that, when locked to a stable optical frequency reference, generates microwave signals with absolute phase noise that is equal to or better than cryogenic microwave oscillators. At 1 Hz offset from a 10 GHz carrier, the phase noise is below -100 dBc/Hz, limited by the optical reference. For offset frequencies > 10 kHz, the phase noise is shot noise limited at -145 dBc/Hz. An analysis of the contribution of the residual noise from the Er:fiber optical frequency divider is also presented.Comment: 4 pages, 3 figure

Miniature narrow-linewidth 1 {\mu}m Laser

Self-injection locking scheme has the potential to narrow the linewidth of lasers in a compact setup. Here, we report a narrow linewidth laser source near 1 {\mu}m by self-injection locking scheme using a Fabry-Perot (FP) hollow resonator with a high-quality factor (Q>10^8). The measured fundamental linewidth of the laser is 41 Hz, and a coarse tuning range over 5.5 nm is achieved by changing the driving current of the laser source. Meanwhile, a fine-tuning range of 373 MHz is achieved without mode hops by changing the voltage applied to the PZT on the resonator. More importantly, benefiting from the low thermal refractive noise and low thermal expansion of the FP hollow resonator, the beat-note linewidth and the frequency Allan deviation are measured to be 510.3 Hz in and 10^-11 (1s averaging time), respectively, by using a fully stabilized frequency comb as reference. Such a high-performance laser is fully integrated with a palm-sized package (52.3 mL) for field-deployable applications

Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin

Background: Our previous work determined the correlation between high nuclear expression of hepatoma-derived growth factor (HDGF) and clinicopathological data of endometrial cancer (EC); however, the modulatory mechanisms and biological role of HDGF in EC have not been reported.Methods: Lentiviral particles carrying human HDGF short hairpin RNA (shHDGF-1, -2, and -3) vector and plasmids for HDGF, DDX5, and β-catenin expression were, respectively introduced into EC cells to evaluate the effects and molecular mechanisms underlying EC cell proliferation, migration, invasion, and metastasis. Quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were used to determine HDGF and DDX5 expression. Co-immunoprecipitation (co-IP), mass spectrometry, and an immunofluorescence co-localization study were conducted to explore the relationship between HDGF, DDX5, and β-catenin. Immunohistochemistry was used to analyze the clinical associations between HDGF and DDX5 in EC.Results: Knocking down HDGF expression significantly decreased EC cellular proliferation, migration, invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, HDGF overexpression reversed these effects. Stable knockdown-based HDGF suppression activated the PI3K/AKT signaling pathway, along with downstream β-catenin-mediated cell cycle and epithelial-mesenchymal transition signaling. Furthermore, co-IP combined with mass spectrometry and an immunofluorescence co-localization study indicated that HDGF interacts with DDX5, whereas β-catenin was associated with DDX5 but not HDGF. Overexpression of DDX5 reversed the suppression of shHDGF. Immunohistochemistry analysis showed that high expression of DDX5 constituted an unfavorable factor with respect to the clinicopathological characteristics of EC tissues and that HDGF and DDX5 high expression (HDGF+/DDX5+) led to a worse prognosis for patients with EC (P &lt; 0.001). In addition, we found that the expression of HDGF and DDX5 was positively correlated in EC tissues (r = 0.475, P &lt; 0.001).Conclusion: Our results provide novel evidence that HDGF interacts with DDX5 and promotes the progression of EC through the induction of β-catenin

Observational studies of the effects of wind mixing and biological process on the vertical distribution of dissolved oxygen off the Changjiang Estuary

Wind mixing is important in regulating dissolved oxygen (DO) variability; however, the transect response of DO dynamics to wind disturbance has seldom been documented with field data. In the summer of 2017, repeat transect observations off the Changjiang Estuary were conducted throughout a fresh wind (the maximum wind speed was 9.8 m s–1) event to reveal the role of physical mixing and biological activity in DO variations. After the wind event, hypoxia was alleviated presenting as the hypoxia thickness decreased from 30 m to 20 m. However, poorly ventilated near-bottom hypoxia was aggravated with a further decrease in DO. Generally, the saturation of dissolved oxygen (DOs) in depth-integrated water column increased by 9%–49% through physical diffusion with a weakened stratification and enhanced phytoplankton bloom. However, in this case, the wind-induced physical water mass mixing by transporting DO downward had a limited contribution to the water-column DO budget, while upwards nutrients induced by mixing fueled the larger vertical area of algae bloom and subsequent substantial oxygen consumption. As the wind speed increased, the air-sea exchange would be important in supplying DO, especially in nearshore areas, which could effectively offset the DO deficiency. In summary, frequently occurring fresh wind-mixing events off the Changjiang Estuary would alleviate hypoxia in the water column but probably exacerbate hypoxia at the bottom, as determined by competing ventilation and respiration roles. Such complex interactions likely occur and perform differently as wind stress varies. Thus, high-spatial and long-term process observations are required to better understand the net effects of bottom hypoxia evolution

Massive nutrients offshore transport off the Changjiang Estuary in flooding summer of 2020

Flood events significantly increase water discharges and terrigenous material inputs to coastal waters. Riverine nutrients in the Changjiang Estuary are transported by the dispersion of Changjiang Diluted Water (CDW) plumes and detached low-salinity water patches. However, the effects of flooding on nutrient offshore transports have not been well explored. Here, we present the nutrient conditions in the Changjiang Estuary and adjacent East China Sea in the historical flooding year 2020. Comparisons of nutrient distributions between flooding years, drought year and non-flooding years were also made. Our results showed that nitrate flux from the Changjiang River in August 2020 was 1.5 times that of the multi-year averaged flux in non-flooding years. Enormous riverine nutrient input resulted in much higher nutrient concentrations in the outer estuary than those in non-flooding years. In addition, a detached low-salinity water patch was observed, which made the salinity of the northern estuary even lower than that in the historical flooding year 1998. Surface dissolved inorganic nitrate (DIN) level in the low-salinity water patch was even ~16 times of that at nearby station in the drought year 2006. While phosphate (PO43−) concentrations were less than 0.1 μmol L−1 east of 123°E, which was probably caused by intensive biological uptake, as indicated by a high Chlorophyll a (Chl a) concentration (29.08 μg L−1). The depleted PO43− and high N/P of the low-salinity water patch suggested PO43− limitation even under flood conditions. A three end-member mixing model was adopted to identify the contributions of the CDW end-member (CDWend-member) and biological process to nutrient distributions. Our model results showed that the nutrient contribution of the CDWend-member to the estuary (122–124°E, 31–32.5°N) in flooding year 2020 was over double that in drought year 2006. Model-derived biological DIN uptake was as high as 24.65 μmol L−1 at the low-salinity water patch. Accordingly, the estimated net community production was 566–1131 mg C m−2 d−1 within the euphotic zone. The offshore transport of a low-salinity, high-DIN water patch during flooding could probably have a significant influence on biogeochemical cycles in the broad shelf, and even the adjacent Japan Sea