[Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics].

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.

Emerging role of m6A methylation modification in ovarian cancer.

m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.

Screening for Early-Stage Parkinson's Disease: Swallow Tail Sign on MRI Susceptibility Map-Weighted Images Compared With PET.

BACKGROUND: Swallow tail sign (STS) on MRI is presumed to be an imaging biomarker of nigrosome-1, which may exhibit a similar role as positron emission tomography (PET), indicating dopaminergic degeneration. PURPOSE: To investigate whether an alteration of STS could serve as an alternative screening sign compared with PET in the diagnosis of early-stage Parkinson's disease (esPD). STUDY TYPE: Prospective. POPULATION: Thirty-seven patients with esPD and 27 age- and sex-matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: Quantitative susceptibility mapping images were collected on 3T MRI and [18 F]9-fluoropropyl-(+)-dihydrotetra-benazine PET images were acquired using a 64 rings PET/CT scanner. ASSESSMENT: Alterations of STS and striatal uptake in each hemisphere were visually rated on a 0-2 points scale. Point 2: normal appearance of STS/normal striatal uptake; Point 1: partial loss of STS/uptake reduction confined to the putamen; Point 0: total loss of STS/uptake reduction extended to the caudate nucleus. The concordance rate of STS rating and ipsilateral striatal binding was calculated at the nuclei level. At the participant level, an evaluation rating was calculated by adding the STS ratings from both hemispheres to distinguish esPD from HCs. STATISTICAL TESTS: The intra- and interobserver agreement were tested using Cohen's kappa and the intraclass correlation coefficient. Hotelling's T-squared test was used to compare the difference of rating points. Receiver operating characteristic analysis was performed to evaluate the diagnostic power. RESULTS: The intra- and interobserver agreement for STS and striatal uptake rating was over 0.75. There was no significant difference of rating point distribution (P = 0.084). The concordance rate was 94.3% for the right side and 91.4% for the left. Using bilateral partial loss of STS as the threshold, the achieved sensitivity and specificity for discriminating esPD from HCs were 94.59% and 92.49%, respectively. DATA CONCLUSION: STS alterations corresponded well with striatal uptake on PET in esPD, and our proposed evaluation scale of STS had satisfactory diagnostic performance in discriminating the disease. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

[Mechanism of paeonol combined with paeoniflorin against myocardial ischemia injury:based on proteomics].

The study aims to investigate the effect of the compatibility of paeonol and paeoniflorin(hereinafter referred to as the compatibility) on the expression of myocardial proteins in rats with myocardial ischemia injury and explore the underlying mechanism of the compatibility against myocardial ischemia injury. First, the acute myocardial infarction rat model was established by ligation of the anterior descending branch of the left coronary artery. The model rats were given(ig) paeonol and paeoniflorin. Then protein samples were collected from rat cardiac tissue and quantified by tandem mass tags(TMT) to explore the differential proteins after drug intervention. The experimental results showed that differential proteins mainly involved phagocytosis engulfment, extracellular space, and antigen binding, as well as Kyoto encyclopedia of genes and genomes(KEGG) pathways of complement and coagulation cascades, syste-mic lupus erythematosus, and ribosome. In this study, the target proteins and related signaling pathways identified by differential proteomics may be the biological basis of the compatibility against myocardial ischemia injury in rats.

Short-echo-time magnitude image derived from quantitative susceptibility mapping could resemble neuromelanin-sensitive MRI image in substantia nigra.

BACKGROUND: In this study, we explored whether the proposed short-echo-time magnitude (setMag) image derived from quantitative susceptibility mapping (QSM) could resemble NM-MRI image in substantia nigra (SN), by quantitatively comparing the spatial similarity and diagnosis performances for Parkinson's disease (PD). METHODS: QSM and NM-MRI were performed in 18 PD patients and 15 healthy controls (HCs). The setMag images were calculated using the short-echo-time magnitude images. Bilateral hyperintensity areas of SN (SNhyper) were manually segmented on setMag and NM-MRI images by two raters in a blinded manner. The inter-rater reliability was evaluated by the intraclass correlation coefficients (ICC) and the Dice similarity coefficient (DSC). Then the inter-modality (i.e. setMag and NM-MRI) spatial similarity was quantitatively assessed using DSC and volume of the consensual voxels identified by both of two raters. The performances of mean SNhyper volume for PD diagnosis on setMag and NM-MRI images were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The SNhyper segmented by two raters showed substantial to excellent inter-rater reliability for both setMag and NM-MRI images. The DSCs of SNhyper between setMag and NM-MRI images showed substantial to excellent voxel-wise overlap in HCs (0.80 ~ 0.83) and PD (0.73 ~ 0.76), and no significant difference was found between the SNhyper volumes of setMag and NM-MRI images in either HCs or PD (p > 0.05). The mean SNhyper volume was significantly decreased in PD patients in comparison with HCs on both setMag images (77.61 mm3 vs 95.99 mm3, p < 0.0001) and NM-MRI images (79.06 mm3 vs 96.00 mm3, p < 0.0001). Areas under the curve (AUCs) of mean SNhyper volume for PD diagnosis were 0.904 on setMag and 0.906 on NM-MRI images. No significant difference was found between the two curves (p = 0.96). CONCLUSIONS: SNhyper on setMag derived from QSM demonstrated substantial spatial overlap with that on NM-MRI and provided comparable PD diagnostic performance, providing a new QSM-based multi-contrast imaging strategy for future PD studies.

Membrane metallo-endopeptidase mediates cellular senescence induced by oncogenic PIK3CAH1047R accompanied with pro-tumorigenic secretome.

The hotspot mutation H1047R in the oncogenic PIK3CA gene is frequently detected in breast cancer and enhances the enzymatic activity of PI3K to activate AKT/mTOR signaling cascade. Aberrant elevated PI3K activation has been reported to promote the tumorigenesis of breast cancer, but the mechanisms underlying are still needed to be elucidated. Here, we found that continuously activating PIK3CAH1047R conferred human mammary epithelial MCF-10A cells to cellular senescence upon serum-starvation. Similarly, breast cancer T47D and HCC1954 cells harboring H1047R mutation were senescent when cells were deprived of serum. PI3K/AKT/mTOR axis but not p53 or RB might be required for the induction of senescence. Notably, membrane metallo-endopeptidase (MME) was identified as a downstream effector of PI3K to mediate the induction of senescence, which might be associated with its glycosylation. Senescent cells elicited a distinct secretome dependent on PI3K and MME. Specifically, IL-6 promoted the proliferation of normal cells and CCL2 induced the M2-like polarization of macrophages, which might create an immunosuppressive microenvironment during the initiation and/or development of breast cancer. This study shed new light on the tumorigenesis induced by hyper-activated PI3K and might provide new clues for the prevention and therapy of breast cancer.

Oncogene-induced senescence: a double edged sword in cancer.

Oncogene-induced cellular senescence (OIS) is a complex program that is triggered in response to aberrant activation of oncogenic signaling. Initially, OIS was thought to be a barrier to malignant transformation because of its suppression on cell proliferation. Later studies showed that senescence induced by oncogenes can also promote the initiation and development of cancer. The opposing effects of OIS occur through different combinations of downstream effectors as well as the interplay of senescent cells and the microenvironment, such as senescence-associated inflammation. Here, we review the common features and molecular mechanisms underlying OIS and the interaction between senescent cells and the microenvironment. We propose that targeting senescent cells may have a beneficial therapeutic effect during the treatment of cancer.

Spray drying the Pickering emulsions stabilized by chitosan/ovalbumin polyelectrolyte complexes for the production of oxidation stable tuna oil microcapsules.

The microencapsulation of polysaturated fatty acids by spray drying remains a challenge due to their susceptibility to oxidation. In this work, antioxidant Pickering emulsions were attempted as feeds to produce oxidation stable tuna oil microcapsules. The results indicated that the association between chitosan (CS) and ovalbumin (OVA) was a feasible way to fabricate antioxidant and wettable complexes and a high CS percentage favored these properties. The particles could yield tuna oil Pickering emulsions with enhanced oxidation stability through high-pressure homogenization, which were successfully spray dried to produce microcapsules with surface oil content of 8.84 % and microencapsulation efficiency of 76.65 %. The microcapsules exhibited significantly improved oxidation stability and their optimum peroxide values after storage at 50 °C, 85 % relative humidity, or natural light for 15 d were 48.67 %, 60.07 %, and 39.69 % respectively lower than the powder derived from the OVA-stabilized emulsion. Hence, Pickering emulsions stabilized by the CS/OVA polyelectrolyte complexes are potential in the production of oxidation stable polyunsaturated fatty acid microcapsules by spray drying.

[Relationship of Chinese medicine syndrome with endothelium-dependent vasodilatation function and carotid intima-media thickness in patients with hypertensive disease].

OBJECTIVE: To explore the relationship of Chinese medicine (CM) syndrome with carotid intima-media thickness (CIMT) and endothelium-dependent vasodilatation function (EDVF) in patients with hypertensive disease (HD) for providing an objective basis of syndrome differentiation in HD patients. METHODS: Color Doppler's ultrasound was used to measure the endothelium-dependent flow-mediated dilation (FMD) of brachial artery and carotid intima-media thickness (CIMT) in 60 HD patients (the HD group) and 30 normal controls (the control group). And the relationship of the outcomes with Chinese medicine syndrome types in patients was analyzed statistically. RESULTS: FMD was lower and CIMT was higher in HD patients of all syndrome types than those in the control group respectively (P<0.01). Comparison between patients of different syndrome types showed that FMD was higher in patients of Gan-fire exuberance type and yin-deficiency and yang-hyperaction type than in those of both yin-yang deficiency type and phlegm-dampness stagnancy type (P<0.01, P<0.05), while CIMT in patients of Gan-fire exuberance type was the lowest in all types, and that in yin-deficiency and yang-hyperaction type was lower than in yin-yang deficiency type (P<0.01). CONCLUSION: CIMT and FMD may be used as a reference index for CM syndrome differentiation in HD patients.

[Reasons and complications of pacemaker replacement operation: clinical analysis of 69 case-times].

OBJECTIVE: To analyze the reasons of cardiac permanent pacemaker replacement and the strategies to prevent relevant complications. METHODS: The clinical data of 57 patients, 38 males and 19 females, aged 74 +/- 8 (56-94), 31 with sick sinus syndrome, 26 with II or III degree atrioventricular block, who underwent 63 times of cardiac permanent pacemaker replacement, including 13 times of lead replacement, were analyzed. RESULTS: The reason of replacement included battery normal exhaustion for 57 case-times, battery exhaustion before the defined schedule for 2 case-times, lead electrodes incompletely fractured for 2 case-times, and infection of pacemaker pocket for 2 case-times. There were 9 cases of placement-related complications: pacemaker pocket hematoma (n=4), lead dislocation (n=3), and abandoned leads falling into the right ventricle (n=2). The average lifetime of old pacemakers was 9. 25 years (2 -15 years). The pacing threshold of ventricular leads after pacemaker replacement was (0.77 +/- 0. 40)V, significantly higher than the initial pacing threshold [(0.60 +/- 0.21)V, P < 0.01]. There were no significant differences in the lead impedance and R wave amplitude between the pacemaker replacement and initial implantation [(854 +/- 136)omega vs. (828 +/- 176)omega, and (12 +/- 4)mV vs. (12 +/- 4)mV, both P > 0.05]. CONCLUSION: The main reason of pacemaker replacement is battery exhaustion. Most implanted ventricular leads still can be used. A rare serious complication of cardiac pacemaker replacement operation is abandoned lead falling into the right ventricle, and correct disposing of initial leads help avoid this complication .

Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3Kα-selective inhibitor CYH33 in breast cancer.

PI3Ks are frequently hyper-activated in breast cancer and targeting PI3Kα has exhibited promising but variable response in preclinical and clinical settings. CYH33 is a novel PI3Kα-selective inhibitor in phase I clinical trial. We investigated the efficacy of CYH33 against breast cancer and explored potential predictive biomarkers. CYH33 potently restrained tumor growth in mice bearing human breast cancer cell xenografts and in R26-Pik3caH1047R;MMTV-Cre transgenic mice. CYH33 significantly inhibited proliferation of a panel of human breast cancer cells, while diversity in sensitivity has been observed. Cells harboring activating PIK3CA mutation, amplified HER2 were more responsive to CYH33 than their counterparts. Besides, cells in HER2-enriched or luminal subtype were more sensitive to CYH33 than basal-like breast cancer. Sensitivity to CYH33 has been further revealed to be associated with induction of G1 phase arrest and simultaneous inhibition of Akt and ERK. Sensitivity of patient-derived xenograft to CYH33 was also positively correlated with decrease in phosphorylated ERK. Taken together, CYH33 is a promising PI3Kα inhibitor for breast cancer treatment and decrease in ERK phosphorylation may indicate its efficacy, which provides useful clues for rational design of the ongoing clinical trials.

[Effects of grape seed addition in swine manure-wheat straw composting on the compost microbial community and carbon and nitrogen contents].

Taking substrates swine manure and wheat straw (fresh mass ratio 10.5:1) as the control (PMW), a composting experiment was conducted in a self-made aerated static composting bin to study the effects of adding 8% grape seed (treatment PMW + G) on the succession of microbial community and the transformation of carbon and nitrogen in the substrates during the composting. Seven samples were collected from each treatment, according to the temperature of the compost during the 30 d composting period. The microbial population and physiological groups were determined, and the NH4(+)-N, NO3(-)-N, organic N, and organic C concentrations in the compost were measured. Grape seed addition induced a slight increase of bacterial count and a significant increase of actinomycetes count, but decreased the fungal count significantly. Grape seed addition also decreased the ratio of bacteria to actinomycetes and the counts of ammonifiers and denitrifiers, but increased the counts of nitrifiers, N-fixing bacteria, and cellulose-decomposing microorganisms. The contents of NH4(+)-N and organic C decreased, while that of NO3(-)-N increased obviously. The NO3(-)-N content in the compost was positively correlated with the actinomycetes count. During composting, the compost temperature in treatment PMW + G increased more rapidly, and remained steady in thermophilic phase, while the water content changed little, which provided a stable and higher population of actinomycetes and nitrifiers in thermophilic phase, being beneficial to the increase of compost nitrate N.