Effect on the splenocyte function of weaned piglets induced by continuous lipopolysaccharide injections.

Introduction: When piglets are exposed to pathogens for a long period, the immune system organs, among them the spleen, play a major role in combating the stress caused by those pathogens. In the present study, the effect on splenocyte function was investigated in a model of weaned piglets in which stress was induced by multiple low doses of lipopolysaccharide (LPS). Material and Methods: Forty-eight 28-day-old piglets were divided into two groups: the LPS group and the control group. During the experimental period of thirteen days, the LPS group was intraperitoneally injected with LPS (100 µg/kg) once per day, and the control group was injected with the same volume of 0.9% sterile saline. On the 1st, 5th, 9th and 13th days, the piglets' spleens were collected for isolating splenocytes. The proliferation ability of splenocytes was evaluated by the cell-counting-kit 8 method. Flow cytometry was used to detect cell cycle stage and apoptosis, and the nitric oxide level of cell supernatant was also tested. Results: In the experimental group, the proliferation ability of splenocytes was enhanced, the proportion of cells in the G0/G1 phase was smaller, and cells were promoted to the S and G2/M phases. Meanwhile, apoptosis was suppressed and nitric oxide release upregulated. The results were significantly different between the LPS group and the control group on the 5th and 9th days. Conclusion: The difference between the results of one group and those of the other suggest that after the 5th LPS injection, multiple low doses of LPS activated splenocytes and restored the number of splenocytes, which maintained and possibly enhanced the regulation of the immune function of the spleen.

Cavity online measurements with a coaxial electrical probe in an X band integrally sealed relativistic klystron amplifier.

The electromagnetic characteristics of the input cavity with electron beams loaded are measured successfully in an X-band triaxial relativistic klystron amplifier (TKA) with a high frequency electrical probe. To solve the frequency response issue in the X band, a coaxial electrical probe is optimized and inserted obliquely into the input cavity at the designed angle so that the microwaves in the cavity can be sampled and extracted with the required coupling coefficient while the probe does not interfere with the solenoid coil, which is tightly integrated outside the TKA. Besides, the TKA is redesigned as a structure integrally sealed by the solenoid coil, and the secondary sealing induced by probe insertion is implemented on the flange of the solenoid coils rather than on the wall of the TKA, which is conducive to simplifying the coupling structure while maintaining the high vacuum level. The design is examined in a GW level TKA experiment, indicating that microwaves with a power of about 670 MW are generated in the input cavity at a frequency of 8.40 GHz, which is completely consistent with the injected and output microwave frequencies.

Coherent Combining of Phase-Steerable High Power Microwaves Generated by Two X-Band Triaxial Klystron Amplifiers with Pulsed Magnetic Fields.

We report the first experimental demonstration of coherent combining of phase-steerable high power microwaves (HPMs) generated by X-band relativistic triaxial klystron amplifier modules under the guidance of pulsed magnetic fields. Electronically agile manipulation of the HPM phase is achieved with a mean discrepancy of 4° at the gain level of 110 dB, and the coherent combining efficiency has reached as high as 98.4%, leading to combined radiations with equivalent peak power of 4.3 GW and average pulse duration of 112 ns. The underlying phase-steering mechanism during the nonlinear beam-wave interaction process is furthermore explored by particle-in-cell simulation and theoretical analysis. This Letter paves the way for high power phase array in large scale and may stimulate new interest in research of phase-steerable high power masers.

Design and experimental research of a compact directional coupler for X-band relativistic triaxial klystron amplifier.

To realize online measurement of power, frequency, and phase for a modularized relativistic triaxial klystron amplifier in a narrow space, a compact directional coupler with high directivity, high power handling capacity, and large bandwidth has been investigated numerically and experimentally. The method with coupling holes distributed in both the longitudinal and lateral directions is proposed, and the simulation results indicate that when two holes are employed, directivity larger than 20 dB is achieved over a 300 MHz bandwidth in the X-band and the maximal electric field strength is controlled to be 198.5 kV/cm with 1 GW power injection, while the whole coupler longitude is optimized to be as short as 50 mm. High power experiments have been performed with a 10 GHz relativistic triaxial klystron amplifier, and the results show that the measured power, frequency, and phase shift of the directional coupler have good agreement with the results obtained in the far-field.

Population genomics of emerging Elizabethkingia anophelis pathogens reveals potential outbreak and rapid global dissemination.

Elizabethkingia anophelis is an emerging species and has increasingly been reported to cause life-threatening infections and even outbreaks in humans. Nevertheless, there is little data regarding the E. anophelis geographical distribution, phylogenetic structure, and transmission across the globe, especially in Asia. We utilize whole-genome sequencing (WGS) data to define a global population framework, phylogenetic structure, geographical distribution, and transmission evaluation of E. anophelis pathogens. The geographical distribution diagram revealed the emerging pathogenic bacteria already distributed in various countries worldwide, especially in the USA and China. Strikingly, phylogenetic analysis showed a part of our China original E. anophelis shared the same ancestor with the USA outbreak strain, which implies the possibility of localized outbreaks and global spread. These closer related strains also contained ICEEaI, which might insert into a disrupted DNA repair mutY gene and made the strain more liable to mutation and outbreak infection. BEAST analysis showed that the most recent common ancestor for ICEEaI E. anophelis was dated twelve years ago, and China might be the most likely recent source of this bacteria. Our study sheds light on the potential possibility of E. anophelis causing the large-scale outbreak and rapid global dissemination. Continued genomic surveillance of the dynamics of E. anophelis populations will generate further knowledge for optimizing future prevent global outbreak infections.

Alterations in the jejunal microbiota and fecal metabolite profiles of rabbits infected with Eimeria intestinalis.

BACKGROUND: Rabbit coccidiosis is a major disease caused by various Eimeria species and causes enormous economic losses to the rabbit industry. Coccidia infection has a wide impact on the gut microbiota and intestinal biochemical equilibrium. In the present study, we established a model of Eimeria intestinalis infection in rabbits to evaluate the jejunal microbiota and fecal metabolite profiles. METHODS: Rabbits in the infected group were orally inoculated with 3 × 103 E. intestinalis oocysts. On the eighth day of infection, jejunal contents and feces were collected for 16S rRNA gene sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, respectively. Jejunum tissues were harvested for hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and immunohistochemistry (IHC) staining. RESULTS: Histopathological analysis showed that the whole jejunum was parasitized by E. intestinalis in a range of life cycle stages, and PAS staining showed that E. intestinalis infection caused extensive loss of goblet cells. IHC staining revealed that TNF-α expression was higher in the E. intestinalis infection group. Moreover, both the jejunal microbiota and metabolites significantly altered after E. intestinalis infection. At the genus level, the abundances of Escherichia and Enterococcus significantly increased in the infected group compared with the control group, while those of Oscillospira, Ruminococcus, Bacteroides, Akkermansia, Coprococcus, and Sarcina significantly decreased. In addition, 20 metabolites and two metabolic pathways were altered after E. intestinalis infection, and the major disrupted metabolic pathway was lipid metabolism. CONCLUSIONS: Eimeria intestinalis infection induced intestinal inflammation and destroyed the intestinal homeostasis at the parasitized sites, leading to significant changes in the gut microbiota and subsequent corresponding changes in metabolites.

Long non-coding RNA NNT-AS1 positively regulates NPM1 expression to affect the proliferation of estrogen-mediated endometrial carcinoma by interacting.

Objective: This study aims to investigate the mechanism of long non-coding RNA NNT-AS1 in the proliferation of estrogen-mediated endometrial carcinoma (EC). Materials and methods: NNT-AS1, miR-30c, and Nucleophosmin 1 (NPM1) expressions were measured by quantitative real-time PCR and Western blotting. Cell Counting Kit-8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay were used to detect the viability and proliferation of Ishikawa and HEC-1-A cells, respectively. RNA immunoprecipitation assay was used to confirm the interaction between NNT-AS1 and miR-30c. Luciferase reporter assay was performed to confirm the interaction between miR-30c and NPM1. Results: NNT-AS1 and NPM1 expressions in EC tissues and cell lines were higher than in benign endometrium and normal endometrial epithelial cells (EECs). miR-30c expression in EC tissues and cell lines was lower than in benign endometrium and normal EECs. NNT-AS1 interacted with miR-30c, and miR-30c negatively regulated NPM1 expression. Overexpression of NNT-AS1 increased NPM1 expression in EC cells, while overexpression of miR-30c reversed the effect. NNT-AS1 interference inhibited the mRNA level of NPM1, while the miR-30c inhibitor reversed the result. Estradiol (E2) promoted the proliferation of EC cells, small interfering RNA (siRNA) against NNT-AS1 inhibited EC cell proliferation, miR-30c inhibitor promoted cell proliferation, and NPM1 siRNA inhibited cell proliferation. E2 increased tumor volume, and NNT-AS1 interference reduced tumor volume in vivo. Conclusion: NNT-AS1 promoted the proliferation of estrogen-mediated EC by regulating miR-30c/NPM1.

Fecal metabolomic analysis of rabbits infected with Eimeria intestinalis and Eimeria magna based on LC-MS/MS technique.

Rabbit coccidiosis is a common parasitic disease leading to economic losses in the rabbit industry. The intestinal flora plays a key role in pathogenesis of coccidiosis, and fecal metabolome mediates host-microbiome interactions as a functional readout of the gut microbiome. In this study, the E. intestinalis-infected and E. magna-infected rabbit models were established to investigate metabolic alterations and metabolic pathways based on LC-MS/MS technique for the first time. Multivariate OPLS-DA analysis was performed to explore differential metabolites. In total, 288 metabolites were detected from infected and uninfected rabbits. The level of 33 metabolites increased and 4 decreased in rabbits infected with E. intestinalis. Eight pathways were significantly perturbed during E. intestinalis infection including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, etc. After rabbits infected with E. magna, 13 metabolites were altered and 7 metabolic pathways were dysregulated. These metabolites and metabolic pathways were mainly involved in tuberculosis, parathyroid hormone synthesis, etc. Besides, 25 metabolites differed in abundance between E. intestinalis infection group and E. magna infection group, the major perturbed metabolic pathways were lipid metabolism and endocrine system, respectively. In general, it is confirmed that E. intestinalis and E. magna infection destroyed the intestinal flora, which caused corresponding changes in metabolites, and provide novel insights into the molecular mechanisms of rabbit-parasite interactions.

Effects of Continuous LPS Induction on Oxidative Stress and Liver Injury in Weaned Piglets.

Due to imperfections in their immune and digestive systems, weaned piglets are susceptible to invasions of the external environment and diseases, especially bacterial infections, which lead to slow growth, tissue damage, and even the death of piglets. Here, a model of weaned piglets induced by Escherichia coli lipopolysaccharide (LPS) was established to explore the effects of continuous low-dose LPS induction on the mechanism of liver injury. A total of forty-eight healthy 28-day-old weaned piglets (weight = 6.65 ± 1.19 kg) were randomly divided into two groups: the CON group and LPS group. During the experimental period of thirteen days, the LPS group was injected intraperitoneally with LPS (100 µg/kg) once per day, and the CON group was treated with the same volume of 0.9% NaCl solution. On the 1st, 5th, 9th, and 13th days, the serum and liver of the piglets were collected for the determination of serum biochemical indexes, an antioxidant capacity evaluation, and histopathological examinations. In addition, the mRNA expression levels of the TLR4 pathway and inflammatory cytokines were detected. The results showed that the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in the serum increased after LPS induction. The activities of total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) in the serum and liver homogenate of the LPS group were lower than those of the CON group, while the malondialdehyde (MDA) content in the serum and the activities of catalase (CAT) and superoxide dismutase (SOD) in the liver of the LPS group were higher than those in the CON group. At the same time, morphological impairment of the livers occurred, including hepatocyte caryolysis, hepatocyte vacuolization, karyopycnosis, and inflammatory cell infiltration, and the mRNA expression levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-10 were upregulated in the livers after LPS induction. The above results were more obvious on the 1st and 5th days of LPS induction, while the trend during the later period was not significant. It was concluded that the oxidative stress and liver injury occurred at the early stage of LPS induction, while the liver damage weakened at the later stage. The weaned piglets probably gradually developed tolerance to the endotoxin after the continuous low-dose induction of LPS.

Rabbit microbiota across the whole body revealed by 16S rRNA gene amplicon sequencing.

BACKGROUND: Rabbit can produce meat, fur and leather, and serves as an important biomedical animal model. Understanding the microbial community of rabbits helps to raise rabbits healthily and better support their application as animal models. RESULTS: In this study, we selected 4 healthy Belgium gray rabbits to collect the microbial samples from 12 body sites, including skin, lung, uterus, mouth, stomach, duodenum, ileum, jejunum, colon, cecum, cecal appendix and rectum. The microbiota across rabbit whole body was investigated via 16S rRNA gene amplicon sequencing. After quality control, 46 samples were retained, and 3,148 qualified ASVs were obtained, representing 23 phyla and 264 genera. Based on the weighted UniFrac distances, these samples were divided into the large intestine (Lin), stomach and small intestine (SSin), uterus (Uter), and skin, mouth and lung (SML) groups. The diversity of Lin microbiota was the highest, followed by those of the SSin, Uter and SML groups. In the whole body, Firmicutes (62.37%), Proteobacteria (13.44%) and Bacteroidota (11.84%) were the most predominant phyla. The relative abundance of Firmicutes in the intestinal tract was significantly higher than that in the non-intestinal site, while Proteobacteria was significantly higher in the non-intestinal site. Among the 264 genera, 35 were the core microbiota distributed in all body sites. Sixty-one genera were specific in the SML group, while 13, 8 and 1 were specifically found in the Lin, SSin and Uter groups, respectively. The Lin group had the most difference with other groups, there were average 72 differential genera between the Lin and other groups. The functional prediction analysis showed that microbial function within each group was similar, but there was a big difference between the intestinal tracts and the non-intestinal group. Notably, the function of microorganism in uterus and mouth were the most different from those in the gastrointestinal sites; rabbit's coprophagy of consuming soft feces possibly resulted in little differences of microbial function between stomach and large intestinal sites. CONCLUSION: Our findings improve the knowledge about rabbit microbial communities throughout whole body and give insights into the relationship of microbial communities among different body sites in health rabbits.

N-methyladenosine reader YTHDF2-mediated long noncoding RNA FENDRR degradation promotes cell proliferation in endometrioid endometrial carcinoma.

Dysregulation of long noncoding RNA (LncRNA) FENDDR has been shown to be closely related to the progression of several cancers. However, its role and upstream regulatory mechanism in endometrioid endometrial carcinoma (EEC) remains unclear. This study was conducted using the cancerous tissues of EEC patients (n = 60), EEC cell lines, and a xenograft mouse model. The expression level of LncRNA FENDRR was decreased and the N-methyladenosine (m6A) methylation levels of LncRNA FENDRR was elevated in cancerous tissues of EEC patients. In vitro experiments demonstrated that YTH domain-containing 2 (YTHDF2), an m6A reader, recognized the abundance of m6A-modified LncRNA FENDRR in EEC cells and promoted its degradation. LncRNA FENDRR overexpression suppressed cell proliferation and facilitated cell apoptosis in the EEC cell line HEC-1B by reducing the protein level of SRY-related HMG box transcription factor 4 (SOX4). Interference of LncRNA FENDRR reversed the inhibitory effect of sh-YTHDF2 on cell proliferation and the promoting effect of sh-YTHDF2 on cell apoptosis in HEC-1B cells by silencing FENDRR. Finally, in vivo experiments confirmed that overexpression of LncRNA FENDRR retarded the growth of EEC cells. In conclusion, YTHDF2-mediated LncRNA FENDRR degradation promotes cell proliferation by elevating SOX4 expression in EEC.

A large-size horn antenna for X-band high power microwave radiations.

We present a comprehensive study on designing a large-size horn antenna for radiating gigawatt-level high power microwaves (HPMs) in X-band. The horn taper angle and aperture dielectric window were optimized to achieve high power capacity, low reflection, and small mechanical deformation. It was particularly found that the HPM radiation patterns depend sensitively on the aperture dielectric plate thickness due to double reflections obeying Fresnel theorem. Theoretical analysis suggests that the optimal thickness should be chosen around integral times of half effective microwave wavelength in the dielectric.

Extensive allele-level remodeling of histone methylation modification in reciprocal F1 hybrids of rice subspecies.

Epigenetic mechanisms play a major role in heterosis, partly as a result of the remodeling of epigenetic modifications in F1 hybrids. Based on chromatin immunoprecipitation-sequencing (ChIP-Seq) analyses, we show that at the allele level extensive histone methylation remodeling occurred for a subset of genomic loci in reciprocal F1 hybrids of Oryza sativa (rice) cultivars Nipponbare and 93-11, representing the two subspecies japonica and indica. Globally, the allele modification-altered loci in leaf or root of the reciprocal F1 hybrids involved ˜12-43% or more of the genomic regions carrying either of two typical histone methylation markers, H3K4me3 (>21 000 genomic regions) and H3K27me3 (>11 000 genomic regions). Nevertheless, at the total modification level, the majority (from ˜43 to >90%) of the modification-altered alleles lay within the range of parental additivity in the hybrids because of concerted alteration in opposite directions, consistent with an overall attenuation of allelic differences in the modifications. Importantly, of the genomic regions that did show non-additivity in total modification level by either marker in the two tissues of hybrids, >80% manifested transgressivity, which involved genes enriched in specific functional categories. Extensive allele-level alteration of H3K4me3 alone was positively correlated with genome-wide changes in allele-level gene expression, whereas at the total level, both H3K4me3 and H3K27me3 remodeling, although affecting just a small number of genes, contributes to the overall non-additive gene expression to variable extents, depending on tissue/marker combinations. Our results emphasize the importance of allele-level analysis in hybrids to assess the remodeling of epigenetic modifications and their relation to changes in gene expression.

Encoding Praise and Criticism During Social Evaluation Alters Interactive Responses in the Mentalizing and Affective Learning Networks.

Verbal communication with evaluative characters of different emotional valence has a considerable impact on the extent to which social relations are facilitated or undermined. Here using functional magnetic resonance imaging, we investigated how the brain acts in response to social praise and criticism, leading to differential affective judgments. We engaged thirty men and women in a task associating sex-balanced, neutral faces with praising or criticizing comments targeting others or objects. A whole-brain analysis revealed that criticism as compared to praise enhanced the activation in the medial prefrontal cortex (mPFC), particularly its dorsal portion, whereas the right amygdala displayed an opposite pattern of changes. Comments on others relative to objects increased the reactivity in the left posterior superior temporal sulcus and posterior cingulate cortex (PCC) such that both praise and criticism of others produced stronger activation in these two regions than their object-targeted counterparts. The interaction of valence and target was identified in the mPFC with greater reactivity in the contrasts of criticism vs. praise in the social context and others- vs. object-targeted criticism. Comments also modulated the functional connectivity of prior activated regions with the left temporoparietal junction, bilateral caudate and left PCC/precuneus showing reduced connectivity in response to social criticism but greatly strengthened connectivity for social praise as compared to non-social counterparts. These neural effects subsequently led to altered likeability ratings for the faces. Neither behavioral nor neural effects observed were influenced by the gender of participants. Taken together, our findings suggest a fundamental interactive role of the mentalizing and affective learning networks in differential encoding of individuals associated with praising or criticizing others, leading to learning of valenced traits and subsequent approach or avoidance responses in social interactions.

Long non-coding RNA NIFK-AS1 inhibits M2 polarization of macrophages in endometrial cancer through targeting miR-146a.

Accumulating evidence suggested that tumor-associated macrophages played crucial roles in the progression of endometrial cancer. The aim of this study was to determine the role of lncRNA NIFK-AS1 in M2-like polarization of macrophages and further to investigate the effect of NIFK-AS1 modulating macrophage polarization on the proliferation, migration and invasion of endometrial cancer cells. Human peripheral blood mononuclear cells and tumor-associated macrophages were isolated from healthy volunteers and endometrial cancer patients, respectively. The expression of NIFK-AS1 and miR-146a were detected by qRT-PCR in tumor-associated macrophages or THP-1 monocytes differentiated macrophages. The expression of NIFK-AS1 and miR-146a were decreased and increased in tumor-associated macrophages of endometrial cancer patients, respectively. NIFK-AS1 overexpression suppressed the IL-4-induced M2 polarization of THP-1 macrophages. Moreover, we found that NIFK-AS1 overexpression inhibited the 17ß-estradiol-induced proliferation, migration and invasion of endometrial cancer cells through suppressing M2-like polarization of macrophages. NIFK-AS1 could interact with miR-146a and increased the expression of Notch1 through downregulating miR-146a. Further experiments revealed that miR-146a overexpression attenuated the effect of NIFK-AS1 on suppressing the M2 polarization of macrophages and the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. These findings indicated that NIFK-AS1 inhibited the M2-like polarization of macrophages via targeting miR-146a, thereby reducing the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. Our study highlights the important role of NIFK-AS1 in regulating the polarization and function of tumor-associated macrophages in endometrial cancer and provides novel insight into the TAMs-mediated progression of endometrial cancer.

Long noncoding RNA HOTAIR mediates the estrogen-induced metastasis of endometrial cancer cells via the miR-646/NPM1 axis.

LncRNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been confirmed to be involved in the tumorigenic progression of endometrial carcinoma (EC). However, the molecular mechanisms of HOTAIR in EC are not fully elucidated. The expression of HOTAIR and miR-646 in human EC tissues was determined by qRT-PCR. The effect of miR-646 on EC cells was assessed by the cell viability, migration, and invasion using CCK-8 assays and transwell assays. RNA-binding protein immunoprecipitation assays and RNA pull-down assays were performed to explore the interaction between HOTAIR and miR-646. The regulation of miR-646 on nucleophosmin 1 (NPM1) was tested using luciferase reporter assays. MiR-646 expression was significantly decreased both in human EC tissues ( n = 23) and cell lines (Ishikawa and HEC-1-A) compared with the control. Moreover, miR-646 expression was negatively related to HOTAIR in human EC tissues ( n = 23). Our results also showed that miR-646 overexpression considerably attenuated the E2-promoted viability, migration, and invasion of Ishikawa and HEC-1-A cells in vitro. In addition, HOTAIR was confirmed to regulate the viability, migration, and invasion of EC cells through negative regulating miR-646. More importantly, we also demonstrated that NPM1 was the target of miR-646, and HOTAIR promoted NPM1 expression through interacting with miR-646 in EC cells. Taken together, our findings presented that HOTAIR could regulate NPM1 via interacting with miR-646, thereby governing the viability, migration, and invasion of EC cells.

Propofol promotes cell apoptosis via inhibiting HOTAIR mediated mTOR pathway in cervical cancer.

OBJECTIVES: Cervical cancer is one of the most common gynecologic malignant tumors. Propofol has been proposed to play a role of antitumor in various cancers. However, the functions and mechanisms of Propofol in cervical cancer is still not clear. METHODS: In vitro, the different concentrations of propofol were co-incubated with cervical cancer cell lines, including Hela, Caski and C-33A cells respectively. The pcDNA-HOTAIR plasmid was transfected into cells after the treatment of 10 µg/ml propofol. The cell viability and apoptosis were detected by MTT assay and TUNEL method. In vivo, propofol was injected into mice of transplantation tumor with Caski cells or with pcDNA-HOTAIR treated Caski cells. RESULTS: Propofol significantly decreased the cell viability and increased the cell apoptosis in Hela, Caski and C-33A cells, while HOTAIR overexpression promoted cell viability and inhibits cell apoptosis. mTOR/p70S6K protein expression levels were also markedly reduced by propofol but the effects were reversed with pcDNA-HOTAIR. In vivo, propofol inhibited the tumor size but had no inhibition effect in HOTAIR overexpression group. CONCLUSION: Propofol inhibited tumor size, cell viability and promoted cell apoptosis via inhibiting mTOR/p70S6K pathway mediated by HOTAIR in cervical cancer.

Curcuma zedoaria (Berg.) Rosc. essential oil and paclitaxel synergistically enhance the apoptosis of SKOV3 cells.

Curcuma zedoaria (Berg.) Rosc. essential oil (CZEO) is the major component of Curcuma zedoaria (Berg.) Rosc., a traditional medicine with antitumor activity. Paclitaxel (PTX) is a first-line chemotherapeutic agent used to treat patients with ovarian cancer. These compounds directly target nuclear DNA, in order to suppress or inhibit tumor cell growth. The present study aimed to determine the synergistic antitumor effects of CZEO and PTX on the SKOV3 human ovarian cancer cell line. SKOV3 cells were treated with CZEO, PTX or a combination of the two and cell viability was detected using cell counting kit-8. In addition, flow cytometry was used to determined cell apoptosis as well as for cell cycle analysis. The morpho-logical changes of apoptosis were assessed using Hoechst 33342 staining and the expression levels of apoptotic pathway proteins, including caspase-3 and poly (ADP-ribose) polymerase (PARP), were quantified using western blot analysis. The cell viability assay indicated that either of these compounds alone or in combination suppressed the growth of SKOV3 cells. Furthermore, flow cytometric analysis indicated that treatment with a combination of CZEO and PTX resulted in increased inhibition of proliferation and induction of apoptosis of SKOV3 cells, as compared with treatment with either of the compounds alone. In addition, the protein expression levels of caspase-3 were increased following treatment with a combination of CZEO and PTX. The results of the present study suggested that CZEO and PTX synergistically enhanced the inhibition of SKOV3 proliferation, and the possible underlying mechanism may be the induction of cell apoptosis and cell cycle arrest. This therefore indicated that PTX supplemented with CZEO may be an effective treatment strategy to decrease the dose and toxicity of PTX.

Ultrasound-guided vacuum-assisted breast biopsy using Mammotome biopsy system for detection of breast cancer: results from two high volume hospitals.

Ultrasound-guided vacuum-assisted breast biopsy (VABB) has been recently regarded as a feasible, effective, minimally invasive and safe method for removal of benign breast lesions without serious complications. The frequency of detection of noninvasive malignant breast lesions by ultrasound-guided VABB is increasing. The aim of this study was to evaluate the role of the ultrasound-guided VABB using Mammotome biopsy system in the early detection of breast cancer. Retrospective review between January 2008 to March 2013 the First Affiliated Hospital, Zhejiang University School of Medicine and Taizhou Hospital, Wenzhou Medical College. From January 2008 to March 2013, a total of 5232 ultrasound-guided VABB procedures were performed in 3985 patients whose mean ages were 36.3 years (range: 16-73). The histological results of 5232 ultrasound-guided VABB were retrospectively reviewed. Ultrasonography follow-up was performed at 3 to 6 month intervals in order to assess recurrence. Two hundred twenty three high risk lesions (comprising 59 papilloma, 57 papillomatosis, and 107 atypical hyperplasia) and 61 malignant lesions (comprising 23 ductal carcinoma in situ, 21 lobular carcinoma in situ, 12 infiltrating ductal carcinoma, and 5 infiltrating mucinous carcinoma) were identified. Sensitivity (100%) and diagnostic accuracy (100%) regarding the detection of malignancy were excellent for ultrasound-guided VABB using Mammotome biopsy system. Our results indicate that ultrasound-guided VABB using Mammotome biopsy system is an accurate technique for the sampling, diagnosis, and early detection of breast cancer. It is recommended that the Mammotome biopsy system could be as the method of choice for detecting nonpalpable early breast cancer.

Estrogen mediated expression of nucleophosmin 1 in human endometrial carcinoma clinical stages through estrogen receptor-α signaling.

BACKGROUND: Endometrial carcinoma is one of the most common gynecologic malignancies. Estrogen plays a critical role in its pathogenesis, but the underlying mechanism is not clear. Nucleophosmin 1 (NPM1), a multifunctional protein involved in many cellular activities, has been implicated in the tumorigenesis processes. However, the role of NPM1 in endometrial carcinogenesis remains to be elucidated. The present study was aimed to elucidate the role of NPM1 in different clinical stages of human endometrial carcinoma and the underlying mechanism of NPM1 action. METHODS: The distribution and expression of NPM1 in normal endometrium, FIGO stages I to IV endometrial carcinoma tissues was analyzed using immunohistochemistry, RT-qPCR and Western blotting. The association between NPM1 expression and estrogen and estrogen receptor signaling was investigated in primary-cultured FIGO stage I endometrial adenocarcinoma cells. RESULTS: A strong positive correlation between NPM1 level and the clinical stage and histological grade of endometrial carcinomas was observed. Expression of NPM1 was up-regulated by estrogen in primary-cultured human endometrial adenocarcinoma cells. Furthermore, estrogen increased NPM1 level via estrogen receptor-α (ERα) signaling, nor estrogen receptor-ß signaling. CONCLUSIONS: Expression of NPM1 was gradually increased with the increase of clinical stages of endometrial carcinomas. Overexpression of NPM1 may play a role in the effects of estrogen on the malignant progression of endometrioid adenocarcinoma via ERα signaling. These findings may extend our understanding of the oncogenesis of steroid hormone-related cancers and have significance for the diagnosis and treatment of this carcinoma.