Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype.

BACKGROUND: Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored. METHODS AND RESULTS: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo. CONCLUSION: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

[Effect of origin, tree age, and harvesting time on content of flavonoids and terpene lactones in Ginkgo Folium].

The content of total flavonol glycosides in Ginkgo Folium in the planting bases was determined by high performance liquid chromatography(HPLC).The samples were extracted by reflux with methanol-25% hydrochloric acid.The HPLC conditions were as follows: Agilent ZORBAX SB-C_(18) column(4.6 mm×250 mm, 5 µm), isocratic elution with mobile phase of 0.4% phosphoric acid solution-methanol(45∶55), flow rate of 1 mL·min~(-1), column temperature of 30 ℃, detection wavelength of 360 nm, and injection vo-lume of 10 µL.A method for the determination of terpene lactones in Ginkgo Folium was established based on ultra-high performance liquid chromatograph-triple-quadrupole/linear ion-trap tandem mass spectrometry(UPLC-QTRAP-MS/MS).The UPLC conditions were as below: gradient elution with acetonitrile-0.1% formic acid, flow rate of 0.2 mL·min~(-1), column temperature of 30 ℃, sample chamber temperature of 10 ℃, and injection volume of 10 µL.The ESI~+and multiple reaction monitoring(MRM) were adopted for the MS.The above methods were used to determine the content of total flavonol glycosides and terpene lactones in 99 batches of Ginkgo Folium from 6 planting bases, and the results were statistically analyzed.The content of flavonoids and terpene lactones in Ginkgo Folium from different origins, from trees of different ages, harvested at different time, from trees of different genders, and processed with different methods was compared.The results showed that the content of total flavonol glucosides in 99 Ginkgo Folium samples ranged from 0.38% to 2.08%, and the total content of the four terpene lactones was in the range of 0.03%-0.87%.The method established in this study is simple and reliable, which can be used for the quantitative analysis of Ginkgo Folium.The research results lay a basis for the quality control of Ginkgo Folium.

Analyses of Wheat Yellow Rust Populations Reveal Sexual Recombination and Seasonal Migration Pattern of Puccinia striiformis f. sp. tritici in Gangu, Northwestern China.

Puccinia striiformis f. sp. tritici is the causal agent of wheat yellow rust with records of regular and severe epidemics in China. This study explored the population dynamics of the yellow rust pathogen in Gangu, northwestern China. In Gangu, the Weihe River runs from west to east and divides Gangu into three regions: North and South mountain, with the valley in between. To study the genetic structure of the pathogen in local populations, samples were collected over 3 years from the three regions at different altitudes both within and between the wheat cropping seasons. A total of 811 P. striiformis f. sp. tritici isolates were successfully genotyped using 16 simple sequence repeat markers. The results suggest that P. striiformis f. sp. tritici can survive year-round in Gangu. The P. striiformis f. sp. tritici populations migrated among the regions, and the migration pattern was not related to altitude. The oversummering populations in the North and South mountain regions were genetically different from each other; and the P. striiformis f. sp. tritici populations collected from the lower altitude in the valley had no relationship with any of the populations collected in the spring or fall, indicating that they too have a different origin. Signatures of random mating were found in the populations collected in both North and South mountain regions, but not in the valley populations.

Genomic Basis of Adaptive Divergence in Leg Length between Ground- and Tree-Dwelling Species within a Bird Family.

Hind limbs of tetrapods vary greatly in length and the variability can be associated with locomotor adaptation. Although the phenotypic evolution has been well documented, the underlying genetic basis remains poorly understood. We address this issue by integrating comparative genomics and functional prediction with a study system consisting of ground-dwelling, long-legged and tree-dwelling, short-legged species within the avian family Paridae. Genome-wide divergence and phenotypic correlation analyses jointly identified five highly divergent genomic regions that are significantly related with the difference in leg length between these two groups. Gene annotation for these regions detected three genes involved in skeletal development, that is, PTPA, BRINP1, and MIGA2, with the first one being under the strongest selection. Furthermore, four single nucleotide polymorphisms (SNPs) in the coding region of PTPA can well distinguish the two groups with distinct leg length. Among the four SNPs, one is non-synonymous mutation, and according to the prediction for protein structure and function, it can affect the 3D structure of the encoded protein by altering the corresponding amino acid's position. The alleles of PTPA were found in all sequenced species of the orders Palaeognathae and Psittaciformes, which typically take a ground locomotion style. A whole-genome scanning across bird species uncovered that the four SNPs are more likely to be present in resident passerines with increased leg length/wing length ratios (a proxy of leg-dependent locomotion efficiency). Our findings provide insight into the molecular evolution of locomotion performance based on leg morphology in birds.

[Retracted] MicroRNA­329 serves a tumor suppressive role in colorectal cancer by directly targeting transforming growth factor beta­1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration and invasion assay data shown in Figs. 2C and 5C were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 3825­3832, 2017; DOI: 10.3892/mmr.2017.7077].

Analysis of microbiota reveals the underlying mechanism of PHF11 in the development of Enterococcus-regulated endometriotic cysts.

Endometriosis (EMS) is a prevalent disease and the etiologies has not uniform. Microbiota is associated with human diseases. To delve into the relationship between EMS and microbiota, Ectopic (EM) and eutopic (EU) endometrial tissues, pharyngeal swabs, and stools were collected from EMS patients. The microbiota composition of EM and EU partially overlapped, with similar taxon numbers and diversity, but the richness levels were significantly different. A comparison of intestinal microbes in healthy individuals (FN) and EMS patients (FE) revealed that the richness of Enterococcus, Pseudomonas, Haemophilus, and Neisseria was enhanced in FE. In addition, Enterococcus-induced mice (EFA) presented with a higher degree of lesion infiltration and a wider distribution of lesions. Proteomic analysis revealed the expression of plant homeodomain finger 11 (PHF11) was notably downregulated in EFA. And the downregulated expression of PHF11 was accompanied by the upregulated expression of interleukin 8 (IL-8). Our findings suggest a potential regulatory mechanism for PHF11 in EMS development.

[Basophil CD63 expression in the blood of the anaphylactic shock rat].

OBJECTIVE: To explore the value of flow cytometry in anaphylactic shock diagnosis by CD63 expression being detected using flow cytometry to conform the activation of basophils. METHODS: Sixteen rats were randomly divided into two groups: control group and anaphylactic shock group. The model of anaphylactic shock rat with ovalbumin injection was established. CD63, CD45 and CD203c antibody combination, flow cytometry was employed to detected blood basophil CD63 expression. Immunofluorescence method was employed to observe the CD63 immunofluorescence staining in the rat lung tissue. RESULTS: (1) Pure basophils were obtained by CD45 and CD203c gating. (2) The percentages of basophils CD63 were (17.34 +/- 2.04)% and (1.52 +/- 0.35)% in the experimental and control group, respectively. The differences between two groups were statistically significant (P < 0.01). (3) Compared with the control group, the expression of CD63 in basophils increased in anaphylactic shock lung tissue. CONCLUSION: The detection of CD63 by flow cytometry could be the supplement of vivo allergic reactions and have good clinical value.

Environmental cadmium exposure induces fetal growth restriction via triggering PERK-regulated mitophagy in placental trophoblasts.

Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3ß-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.

Entanglement criterion independent on observables for multipartite Gaussian states based on uncertainty principle.

Quantum entanglement is one of important resources for quantum communication. Entanglement criteria help us detect entangled states. One of important criteria is the local uncertainty relation (LUR) entanglement criteria, which is studied extensively. However, all existent LUR criteria are dependent on the chosen observables. In the paper, applying the uncertainty principle, we improve the LUR criteria to obtain entanglement criteria for multipartite Gaussian states, which are independent on observalbes.

MicroRNA­329 serves a tumor suppressive role in colorectal cancer by directly targeting transforming growth factor beta­1.

Colorectal cancer (CRC) is the third most common type of diagnosed cancer and the fourth leading cause of cancer­associated mortalities worldwide. Increasing studies have demonstrated that the deregulation of microRNAs (miRNAs or miRs) is associated with the occurrence and development of multiple types of human cancer, including CRC. miR­329 has been identified to be downregulated in various types of cancer; however, its expression pattern, functions and mechanisms in CRC remain unclear. The present study demonstrated that miR­329 was lowly expressed in CRC tissue samples and cell lines. Low expression of miR­329 was correlated with tumor­node­metastasis stage and lymph node metastasis in patients with CRC. In vitro experiments revealed that resumption expression of miR­329 suppressed cell proliferation and invasion in CRC. Furthermore, the results of the present study indicated that miR­329 targets transforming growth factor­ß1 (TGF­ß1) directly in vitro. TGF­ß1 was demonstrated to be upregulated in CRC tissue samples and inversely correlated with miR­329 expression. Upregulation of TGF­ß1 was able to partially counteract the antitumor roles of miR­329 on CRC cell proliferation and invasion. The results of the current study revealed that miR­329 suppresses CRC cell proliferation and invasion through targeting TGF­ß1, thus suggesting that targeting miR­329/TGF­ß1 may provide a novel effective therapeutic approach for the treatment of patients with CRC.