A Strategy for Enhancing Perpendicular Magnetic Anisotropy in Yttrium Iron Garnet Films.

In future information storage and processing, magnonics is one of the most promising candidates to replace traditional microelectronics. Yttrium iron garnet (YIG) films with perpendicular magnetic anisotropy (PMA) have aroused widespread interest in magnonics. Obtaining strong PMA in a thick YIG film with a small lattice mismatch (η) has been fascinating but challenging. Here, a novel strategy is proposed to reduce the required minimum strain value for producing PMA and increase the maximum thickness for maintaining PMA in YIG films by slight oxygen deficiency. Strong PMA is achieved in the YIG film with an η of only 0.4% and a film thickness up to 60 nm, representing the strongest PMA for such a small η reported so far. Combining transmission electron microscopy analyses, magnetic measurements, and a theoretical model, it is demonstrated that the enhancement of PMA physically originates from the reduction of saturation magnetization and the increase of magnetostriction coefficient induced by oxygen deficiency. The Gilbert damping values of the 60-nm-thick YIG films with PMA are on the order of 10-4 . This strategy improves the flexibility for the practical applications of YIG-based magnonic devices and provides promising insights for the theoretical understanding and the experimental enhancement of PMA in garnet films.

A Wearable Fluorescence Imaging Device for Intraoperative Identification of Human Brain Tumors.

Malignant glioma (MG) is the most common type of primary malignant brain tumors. Surgical resection of MG remains the cornerstone of therapy and the extent of resection correlates with patient survival. A limiting factor for resection, however, is the difficulty in differentiating the tumor from normal tissue during surgery. Fluorescence imaging is an emerging technique for real-time intraoperative visualization of MGs and their boundaries. However, most clinical grade neurosurgical operative microscopes with fluorescence imaging ability are hampered by low adoption rates due to high cost, limited portability, limited operation flexibility, and lack of skilled professionals with technical knowledge. To overcome the limitations, we innovatively integrated miniaturized light sources, flippable filters, and a recording camera to the surgical eye loupes to generate a wearable fluorescence eye loupe (FLoupe) device for intraoperative imaging of fluorescent MGs. Two FLoupe prototypes were constructed for imaging of Fluorescein and 5-aminolevulinic acid (5-ALA), respectively. The wearable FLoupe devices were tested on tumor-simulating phantoms and patients with MGs. Comparable results were observed against the standard neurosurgical operative microscope (PENTERO® 900) with fluorescence kits. The affordable and wearable FLoupe devices enable visualization of both color and fluorescence images with the same quality as the large and expensive stationary operative microscopes. The wearable FLoupe device allows for a greater range of movement, less obstruction, and faster/easier operation. Thus, it reduces surgery time and is more easily adapted to the surgical environment than unwieldy neurosurgical operative microscopes. Clinical and Translational Impact Statement-The affordable and wearable fluorescence imaging device developed in this study enables neurosurgeons to observe brain tumors with the same clarity and greater flexibility compared to bulky and costly operative microscopes.

Comparative analysis of the phenolic contents and antioxidant activities of different parts of two pomegranate (Punica granatum L.) Cultivars: 'Tunisia' and 'Qingpi'.

Pomegranate (Punica granatum L.), with its abundant phenolic substances and strong antioxidant activity, holds significant research and utilization potential across various organs. However, there have been few studies on the phenolic content and antioxidant activity of different parts of pomegranate, especially the placenta. This study investigated the phenolic content and antioxidant activity of fruits, flowers, and leaves of two pomegranate varieties, 'Tunisia' and 'Qingpi', throughout their growth and development. Results indicated significant variations in phenolic content among different organs, with petals exhibiting the highest total polyphenol content (TPC, 49.40 mg GAE/g FW) and total anthocyanin content (TMAC, 1938.54 nmol/g FW). Placenta contained the highest levels of total flavonoids (TFC, 173.58 mg RE/g FW) and punicalagin (109.30 mg/g FW). The peel had the highest content of total flavanols (TFAC, 19.42 mg CE/g FW). Over the course of pomegranate development, total polyphenols, total flavonoids, total flavanols, punicalagin, and antioxidant activity declined in different organs. Antioxidant activity followed the order: fruit > flower > leaf, with the placenta exhibiting the highest antioxidant activity among fruits. Antioxidant activity showed a significant positive correlation with total polyphenols (R2 = 0.77-1.00), total flavonoids (R2 = 0.71-0.99, except tegmens), and punicalagin (R2 = 0.71-1.00). This study provides a comparative analysis of the phenolic content and antioxidant activity in different organs of pomegranate, highlighting the placenta as the primary source of punicalagin. This study provides a theoretical basis for the development and utilization of pomegranate phenolic compounds.

Small molecule inhibitors of mammalian glycosylation.

Glycans are one of the fundamental biopolymers encountered in living systems. Compared to polynucleotide and polypeptide biosynthesis, polysaccharide biosynthesis is a uniquely combinatorial process to which interdependent enzymes with seemingly broad specificities contribute. The resulting intracellular cell surface, and secreted glycans play key roles in health and disease, from embryogenesis to cancer progression. The study and modulation of glycans in cell and organismal biology is aided by small molecule inhibitors of the enzymes involved in glycan biosynthesis. In this review, we survey the arsenal of currently available inhibitors, focusing on agents which have been independently validated in diverse systems. We highlight the utility of these inhibitors and drawbacks to their use, emphasizing the need for innovation for basic research as well as for therapeutic applications.

Intraoperative Optical and Fluorescence Imaging of Blood Flow Distributions in Mastectomy Skin Flaps for Identifying Ischemic Tissues.

SUMMARY: Insufficient blood flow causes mastectomy skin flap necrosis in 5 to 30 percent of cases. Fluorescence angiography with the injection of indocyanine green dye has shown high sensitivities (90 to 100 percent) but moderate specificities (72 to 50 percent) in predicting mastectomy skin flap necrosis. However, a number of challenging issues limit its wide acceptance in clinical settings, including allergic reaction, short time-window for observation, and high cost for equipment and supplies. An emerging inexpensive speckle contrast diffuse correlation tomography technology enables noninvasive, noncontact, and continuous three-dimensional imaging of blood flow distributions in deep tissues. This preliminary study tested the hypothesis that speckle contrast diffuse correlation tomography and indocyanine green-fluorescence angiography measurements of blood flow distributions in mastectomy skin flaps are consistent. Eleven female patients undergoing skin-sparing or nipple-sparing mastectomies were imaged sequentially by the dye-free speckle contrast diffuse correlation tomography and dye-based commercial fluorescence angiography (SPY-PHI). Resulting images from these two imaging modalities were co-registered based on the ischemic areas with the lowest blood flow values. Because the ischemic areas have irregular shapes, a novel contour-based algorithm was used to compare three-dimensional images of blood flow distribution and two-dimensional maps of indocyanine green perfusion. Significant correlations were observed between the two measurements in all contours from a selected area of 10 × 10 mm 2 with the lowest blood flow ( r ≥ 0.78; p < 0.004), suggesting that speckle contrast diffuse correlation tomography provides the information for identifying ischemic tissues in mastectomy skin flaps. With further optimization and validation in large populations, speckle contrast diffuse correlation tomography may ultimately be used as a noninvasive and inexpensive imaging tool for intraoperative assessment of skin flap viability to predict mastectomy skin flap necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

AD-linked R47H-TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation.

The hemizygous R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific gene in the brain, increases risk for late-onset Alzheimer's disease (AD). Using transcriptomic analysis of single nuclei from brain tissues of patients with AD carrying the R47H mutation or the common variant (CV)­TREM2, we found that R47H-associated microglial subpopulations had enhanced inflammatory signatures reminiscent of previously identified disease-associated microglia (DAM) and hyperactivation of AKT, one of the signaling pathways downstream of TREM2. We established a tauopathy mouse model with heterozygous knock-in of the human TREM2 with the R47H mutation or CV and found that R47H induced and exacerbated TAU-mediated spatial memory deficits in female mice. Single-cell transcriptomic analysis of microglia from these mice also revealed transcriptomic changes induced by R47H that had substantial overlaps with R47H microglia in human AD brains, including robust increases in proinflammatory cytokines, activation of AKT signaling, and elevation of a subset of DAM signatures. Pharmacological AKT inhibition with MK-2206 largely reversed the enhanced inflammatory signatures in primary R47H microglia treated with TAU fibrils. In R47H heterozygous tauopathy mice, MK-2206 treatment abolished a tauopathy-dependent microglial subcluster and rescued tauopathy-induced synapse loss. By uncovering disease-enhancing mechanisms of the R47H mutation conserved in human and mouse, our study supports inhibitors of AKT signaling as a microglial modulating strategy to treat AD.

Evaluation of antioxidant network proteins as novel prognostic biomarkers for head and neck cancer patients.

OBJECTIVES: Recurrence rates for head and neck squamous cell carcinoma (HNSCC) approach 50% at 5 years. Current staging fails to identify patients with a worse prognosis who might benefit from intensified treatment, which warrants improved prognostic biomarkers. The purpose of this retrospective case study is to identify potential prognostic biomarkers in patients with HNSCC including APE1 (DNA repair/redox gene regulator), NRF2 and PPARGC1A (redox gene regulators), SOD3 and DCN (antioxidant proteins). MATERIALS AND METHODS: Differential protein expression between benign, carcinoma in situ (CIS), and invasive HNSCC tissue specimens from 77 patients was assessed using immunohistochemistry. Protein expression was analyzed with multivariate, pair-wise, and Kaplan-Meier survival analyses to identify potential prognostic biomarkers. Utilizing The Cancer Genome Atlas's transcriptome database, pair-wise and survival analysis was performed to identify potential prognostic biomarkers. RESULTS: APE1, NRF2, PPARGC1A, SOD3, and DCN expression in HNSCC in relation to, lymph node invasion, and patient survival were examined. Elevated APE1 protein expression in CIS corresponded with reduced survival (p = 0.0243). Increased APE1 gene expression in stage T4a HNSCC was associated with reduced patient survival (p < 0.015). Increased PPARGC1A in invasive tumor correlated with reduced survival (p = 0.0281). Patients with lymph node invasion at diagnosis had significantly increased APE1 protein in the primary sites (p < 0.05). Patients with poorly differentiated invasive tumors had reduced PPARGC1A in CIS proximal to the invasive tumor and had elevated DCN and SOD3 in proximal benign tissue (p < 0.05). CONCLUSIONS: The expression of APE1, DCN, and SOD3 is a potential prognostic signature that identifies patients with worsened survival.

N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine attenuates oxygen-glucose deprivation and reoxygenation-induced cerebral ischemia-reperfusion injury via regulation of microRNAs.

Cerebral ischemia-reperfusion injury is a common complication that occurs during stroke treatment. Increasingly, microRNAs have been found to participate in the modulation of neuron function; however, the role of microRNAs in cerebral ischemia-reperfusion injury remains unclear. We developed a mechanism of cerebral ischemia-reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation-induced injury in human neuroblastoma SH-SY5Y cells. We found that treatment of oxygen-glucose deprivation and reoxygenation promoted the apoptosis of SH-SY5Y cells. Analysis of microRNAs sequencing revealed that the expression of microRNA-27a-5p was induced, and microRNA-29b-3p expression was inhibited in neuroblastoma cells exposed to oxygen-glucose deprivation and reoxygenation. Either inhibition of microRNA-27a-5p or overexpression of microRNA-29b-3p mitigated oxygen-glucose deprivation and reoxygenation-induced cellular apoptosis. Bach1 was authenticated as a target gene of microRNA-27a-5p. Also, microRNA-27a-5p mediated the expression of Bach 1 along with its downstream signaling. N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protected against oxygen-glucose deprivation and reoxygenation-induced apoptosis while decreasing miR-27a-5p expression and increasing microRNA-29b-3p expression. These results suggested that microRNA-27a-5p and microRNA-29b-3p may contribute to oxygen-glucose deprivation and reoxygenation-induced cellular injury. At the same time, N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protects SH-SY5Y cells against oxygen-glucose deprivation and reoxygenation-induced injury partly through the inhibition of microRNA-27-a-5p and promotion of the Bach1/HO-1 signaling pathway.

ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of prostate cancer by sponging miR-4739 to upregulate MEF2D.

Prostate cancer (PCa) is a destructive malignancy with a bad prognosis. LncRNA VPS9D1-AS1 has recently been delineated as an oncogene in some kinds of tumor, whereas, the function of VPS9D1-AS1 in PCa remains to be clarified. In this study, we researched its underlying role in PCa. The expression of VPS9D1-AS1 was conspicuously upregulated in PCa tissues and cells. And absence of VPS9D1-AS1 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in PCa. In addition, VPS9D1-AS1 overexpression led to opposite results. Furthermore, VPS9D1-AS1/MEF2D could sponge with miR-4739. VPS9D1-AS1/MEF2D and miR-4739 were inversely correlated in tumor cells. And the expression of miR-4739 is markedly downregulated in PCa, meanwhile, that of MEF2D exhibited the opposite tendency. However, MEF2D was positively regulated by VPS9D1-AS1. Moreover, MEF2D upregulation offset the suppressive effects of VPS9D1-AS1 deficiency on cell proliferation, migration and invasion in PCa. Additionally, ZEB1 contained the binding sites of VPS9D1-AS1 promoter, and there existed positive relation between them. Taken together, above results illustrated that ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of PCa by sponging miR-4739 to upregulate MEF2D, which offering a new useful reference for studying the development process of PCa.

Accurate quantification of astrocyte and neurotransmitter fluorescence dynamics for single-cell and population-level physiology.

Recent work examining astrocytic physiology centers on fluorescence imaging, due to development of sensitive fluorescent indicators and observation of spatiotemporally complex calcium activity. However, the field remains hindered in characterizing these dynamics, both within single cells and at the population level, because of the insufficiency of current region-of-interest-based approaches to describe activity that is often spatially unfixed, size-varying and propagative. Here we present an analytical framework that releases astrocyte biologists from region-of-interest-based tools. The Astrocyte Quantitative Analysis (AQuA) software takes an event-based perspective to model and accurately quantify complex calcium and neurotransmitter activity in fluorescence imaging datasets. We apply AQuA to a range of ex vivo and in vivo imaging data and use physiologically relevant parameters to comprehensively describe the data. Since AQuA is data-driven and based on machine learning principles, it can be applied across model organisms, fluorescent indicators, experimental modes, and imaging resolutions and speeds, enabling researchers to elucidate fundamental neural physiology.

Prostate carcinoma cell-derived exosomal MicroRNA-26a modulates the metastasis and tumor growth of prostate carcinoma.

Prostate carcinoma may develop into metastatic castration-resistant prostate carcinoma (mCRPC) after endocrine therapy. Exosomal microRNAs play an important role in the regulation of tumor microenvironment. Our study aimed to investigate the effect of exosomal miR-26a on tumor phenotype of prostate carcinoma. Low-grade prostate carcinoma cell line (LNCAP) and mCRPC cell line (PC-3) were treated as experimental subjects according to their miR-26a expressions. Wound healing, transwell and colony-forming unit assays were performed after miR-26a mimic/inhibitor transfection. Then, exosomes were isolated from LNCAP and PC-3 cells, and the levels of exosomal miR-26a were determined. After co-culture of LNCAP (PC-3) cells with PC-3 (LNCAP) exosomes, changes in malignant behaviors were measured. Moreover, LNCAP/PC-3 exosomes were injected into xenograft tumor mice to determine effects of the exosomes on tumorigenicity of LNCAP and PC-3 cells. MiR-26a showed a potently inhibitory effect on cell proliferation, migration and invasion of LNCAP and PC-3 cells. LNCAP exosomes had a higher miR-26a level, compared with PC-3 exosomes. Overexpression of miR-26a attenuated the enhanced malignant behavior of LNCAP cells induced by PC-3 exosomes, and miR-26a inhibition could reverse the inhibitory effects of LNCAP exosomes on PC-3 cells. Exosomal miR-26a could significantly alter the expressions of epithelial-mesenchymal transition (EMT)-related factors. Moreover, LNCAP exosomes suppressed the tumorigenicity of PC-3 cells, while PC-3 exosomes could promote the tumorigenicity of LNCAP cells. Our data suggest that exosomal miR-26a derived from prostate carcinoma cells had a suppressive effect on the metastasis and tumor growth of prostate carcinoma.

Single-Cell Transcriptomics Uncovers Glial Progenitor Diversity and Cell Fate Determinants during Development and Gliomagenesis.

The identity and degree of heterogeneity of glial progenitors and their contributions to brain tumor malignancy remain elusive. By applying lineage-targeted single-cell transcriptomics, we uncover an unanticipated diversity of glial progenitor pools with unique molecular identities in developing brain. Our analysis identifies distinct transitional intermediate states and their divergent developmental trajectories in astroglial and oligodendroglial lineages. Moreover, intersectional analysis uncovers analogous intermediate progenitors during brain tumorigenesis, wherein oligodendrocyte-progenitor intermediates are abundant, hyper-proliferative, and progressively reprogrammed toward a stem-like state susceptible to further malignant transformation. Similar actively cycling intermediate progenitors are prominent components in human gliomas with distinct driver mutations. We further unveil lineage-driving networks underlying glial fate specification and identify Zfp36l1 as necessary for oligodendrocyte-astrocyte lineage transition and glioma growth. Together, our results resolve the dynamic repertoire of common and divergent glial progenitors during development and tumorigenesis and highlight Zfp36l1 as a molecular nexus for balancing glial cell-fate decision and controlling gliomagenesis.

Asymmetric independence modeling identifies novel gene-environment interactions.

Most genetic or environmental factors work together in determining complex disease risk. Detecting gene-environment interactions may allow us to elucidate novel and targetable molecular mechanisms on how environmental exposures modify genetic effects. Unfortunately, standard logistic regression (LR) assumes a convenient mathematical structure for the null hypothesis that however results in both poor detection power and type 1 error, and is also susceptible to missing factor, imperfect surrogate, and disease heterogeneity confounding effects. Here we describe a new baseline framework, the asymmetric independence model (AIM) in case-control studies, and provide mathematical proofs and simulation studies verifying its validity across a wide range of conditions. We show that AIM mathematically preserves the asymmetric nature of maintaining health versus acquiring a disease, unlike LR, and thus is more powerful and robust to detect synergistic interactions. We present examples from four clinically discrete domains where AIM identified interactions that were previously either inconsistent or recognized with less statistical certainty.

DBS: a fast and informative segmentation algorithm for DNA copy number analysis.

BACKGROUND: Genome-wide DNA copy number changes are the hallmark events in the initiation and progression of cancers. Quantitative analysis of somatic copy number alterations (CNAs) has broad applications in cancer research. With the increasing capacity of high-throughput sequencing technologies, fast and efficient segmentation algorithms are required when characterizing high density CNAs data. RESULTS: A fast and informative segmentation algorithm, DBS (Deviation Binary Segmentation), is developed and discussed. The DBS method is based on the least absolute error principles and is inspired by the segmentation method rooted in the circular binary segmentation procedure. DBS uses point-by-point model calculation to ensure the accuracy of segmentation and combines a binary search algorithm with heuristics derived from the Central Limit Theorem. The DBS algorithm is very efficient requiring a computational complexity of O(n*log n), and is faster than its predecessors. Moreover, DBS measures the change-point amplitude of mean values of two adjacent segments at a breakpoint, where the significant degree of change-point amplitude is determined by the weighted average deviation at breakpoints. Accordingly, using the constructed binary tree of significant degree, DBS informs whether the results of segmentation are over- or under-segmented. CONCLUSION: DBS is implemented in a platform-independent and open-source Java application (ToolSeg), including a graphical user interface and simulation data generation, as well as various segmentation methods in the native Java language.

Noncontact speckle contrast diffuse correlation tomography of blood flow distributions in tissues with arbitrary geometries.

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the anomaly with blood flow contrast. Importantly, the innovative integration design with one single-EMCCD camera for both PST and scDCT data collection obviates the need for offline alignment of sources and detectors on the tissue boundary. The in vivo imaging capability of the updated scDCT is demonstrated by imaging dynamic changes in forearm blood flow distribution during a cuff-occlusion procedure. The feasibility and safety in clinical use are evidenced by intraoperative imaging of mastectomy skin flaps and comparison with fluorescence angiography.

Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.

Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability.

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.

BACKGOUND: The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets. METHODS: Here we describe the human arterial proteome and proteomic features strongly associated with early atherosclerosis based on mass spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling, and bioinformatic analyses defined the composition, network rewiring, and likely regulatory features of the protein networks associated with early atherosclerosis and how they vary across 2 anatomic distributions. RESULTS: The data document significant differences in mitochondrial protein abundance between coronary and aortic samples (coronary>>aortic), and between atherosclerotic and normal tissues (atherosclerotic<

Long noncoding RNA BDNF-AS is associated with clinical outcomes and has functional role in human prostate cancer.

BACKGROUND: The underlying molecular mechanisms of prostate cancer (CaP) are largely unknown. We investigated the expression, prognostic value and functional role of long non-coding RNA (lncRNA) brain-derived neurotrophin factor antisense (BDNF-AS) in CaP. METHODS: Clinical tumor samples were excised from patients with CaP. Their endogenous BDNF-AS expression levels were evaluated by qRT-PCR. Correlations between CaP patients' endogenous BDNF-AS expression and their clinicopathological factors, overall survival were statistically analyzed. BDNF-AS expression levels were also probed in immortal CaP cell lines. In LNCaP and PC-3 cells, BDNF-AS was ectopically overexpressed through lentiviral transduction. The functions of BDNF-AS upregulation on CaP cell development were evaluated both in vitro and in vivo. RESULTS: BDNF-AS was downregulated in human CaP tumors. Low BDNF-AS expression was correlated with CaP patients' poor prognosis and shorter overall survival. BDNF-AS was also found to be lowly expressed in CaP cell lines. In LNCaP and PC-3 cells, lentivirus-driven BDNF-AS overexpression exerted significantly tumor-suppressing effects on hindering cancer cell proliferation and invasion in vitro, and explant growth in vivo. CONCLUSION: Downregulated BDNF-AS in CaP patients could be a potential prognostic biomarker for predicating poor prognosis and survival. Upregulating BDNF-AS may be a novel molecular intervening target for CaP treatment.

Study on miRNAs' expression for the invasion of pituitary adenomas.

AIM: To explore the possible invasive effect of four microRNAs in invasive pituitary adenomas. MATERIAL AND METHODS: Based on our previous studies, several in silico algorithms, and relative literatures, 30 Han Chinese patients with invasive pituitary adenomas and 30 with non-invasive pituitary adenomas were involved in this research. The proteins related to invasion underwent immunohistochemical staining, including basic fibroblast growth factor (FGF2), pituitary tumor transforming gene (PTTG), cyclin B1 (CCNB1), survivin, focal adhesion kinase (FAK), and microvessel density (MVD). To validate the effect of microRNAs, miR-24, miR-93, miR-126, and miR-34a were chosen as possible targets for the aforementioned proteins with four in silico algorithms. All microRNAs tests were performed using quantitative real-time polymerase chain reaction (qPCR). RESULTS: In our study, FGF2, FAK, PTTG, CCNB1, and MVD were overexpressed in the invasive group compared with the non-invasive group, while an increase in the expression of survivin in the invasive group did not achieve statistical significance. This paper reviewed the literature, and four microRNAs involving invasion were selected for study: miR-24, miR-34a, miR-93, and miR-126. Under-expression of miR-24, miR-34a, and miR-93 was significant in the invasive group, while a decrease of miR-126 expression in the invasive group did not achieve statistical significance. CONCLUSION: FGF2, PTTG, CCNB1, survivin, FAK, and MVD proteins of pituitary adenoma showed strong expression in invasive tumors. Furthermore, miR-24, miR-93, miR-34a, and miR-126 were under-expressed in invasive Pituitary adenomas compared with non-invasive ones. The results indicated some relationship between the miRNA and protein expression during the pituitary invasion process.