Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder.

Bipolar disorder (BD) is a complex psychiatric disorder with strong heritability. Identification of new BD risk genes will help determine the mechanism underlying disease pathogenesis. In the present study, we carried out whole genome sequencing for a Chinese BD family with three affected members and three unaffected members, and identified multiple candidate causal variations, including a frameshift mutation in the GOLGB1 gene. Since a GOLGB1 missense mutation was also found in another BD pedigree, we carried out functional studies by downregulating Golgb1 expression in the brain of neonatal mice. Golgb1 deficiency had no effect on anxiety, memory, and social behaviors in young adult mice. However, we found that young adult mice with Golgb1 deficiency exhibited elevated locomotor activity and decreased depressive behaviors in the tail suspension test and the sucrose preference test, but increased depressive behaviors in the forced swim test, resembling the dual character of BD patients with both mania and depression. Moreover, Golgb1 downregulation reduced PSD93 levels and Akt phosphorylation in the brain. Together, our results indicate that GOLGB1 is a strong BD risk gene candidate whose deficiency may result in BD phenotypes possibly through affecting PSD93 and PI3K/Akt signaling.

Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: potential non-invasive diagnostic and therapeutic biomarkers.

BACKGROUNDS: Salivary biomarkers hold huge potential for the non-invasive diagnosis of oral squamous cell carcinoma. Angiogenic factors and matrix-metalloproteinases (MMPs) are highly expressed in OSCC tissue, but their expression patterns in the saliva are unknown. This study aimed to analyze the levels of angiogenic factors and MMPs in tumor tissue and saliva of OSCC patients. METHODS: OSCC-tissue, adjacent normal tissue (ANT), saliva from OSCC patients, and healthy controls were obtained. The expression patterns of angiogenic factors and MMPs were analyzed by immunohistochemistry, protein chip array, and RT-qPCR. RESULTS: Results showed higher expression of ANG, ANG-2, HGF, PIGF, VEGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in OSCC-tissues compared to the ANT. Among the overexpressed markers in OSCC-tissues, HGF, VEGF, PIGF, PDGF-BB, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were significantly upregulated in the saliva of OSCC patients compared to healthy controls. CONCLUSIONS: The levels of HGF, VEGF, PIGF, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were upregulated both in OSCC tissue and saliva of OSCC patients. Bioinformatic analysis revealed the correlation of these factors with patient survival and cancer functional states in head and neck cancer, indicating these factors as possible saliva-based non-invasive diagnostic/prognostic markers and therapeutic targets of OSCC.

Underdetermined DOA Estimation for Wideband Signals via Focused Atomic Norm Minimization.

In underwater acoustic signal processing, direction of arrival (DOA) estimation can provide important information for target tracking and localization. To address underdetermined wideband signal processing in underwater passive detection system, this paper proposes a novel underdetermined wideband DOA estimation method equipped with the nested array (NA) using focused atomic norm minimization (ANM), where the signal source number detection is accomplished by information theory criteria. In the proposed DOA estimation method, especially, after vectoring the covariance matrix of each frequency bin, each corresponding obtained vector is focused into the predefined frequency bin by focused matrix. Then, the collected averaged vector is considered as virtual array model, whose steering vector exhibits the Vandermonde structure in terms of the obtained virtual array geometries. Further, the new covariance matrix is recovered based on ANM by semi-definite programming (SDP), which utilizes the information of the Toeplitz structure. Finally, the Root-MUSIC algorithm is applied to estimate the DOAs. Simulation results show that the proposed method outperforms other underdetermined DOA estimation methods based on information theory in term of higher estimation accuracy.

mRNA and P-element-induced wimpy testis-interacting RNA profile in chemical-induced oral squamous cell carcinoma mice model.

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs), a novel class of noncoding RNAs, are involved in the carcinogenesis. However, the functional significance of piRNAs in oral squamous cell carcinoma (OSCC) remains unknown. In the present study, we used chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) induced OSCC mouse model. piRNAs and mRNAs were profiled using next-generation sequencing in the tongue tumor tissues from 4NQO induction and healthy tongue tissues from control mice. Furthermore, we analyzed the differential gene expression of human OSCC in Gene Expression Omnibus (GEO) database. According to the common differentially expressed genes in the 4NQO model and human OSCC tissues, piRNAs and mRNAs network were established based on informatics method. A total of 14 known piRNAs and 435 novel predicted piRNAs were differently expressed in tumor tissue compared to healthy tissue. Among differently expressed piRNAs 260 were downregulated, and 189 were upregulated. The mRNA targets for the differentially expressed piRNAs were identified using RNAhybrid software. Primary immunodeficiency and herpes simplex infection were the most enriched pathways. A total of 22 mRNAs overlapped in human and mice OSCC. Moreover, we established the regulatory network of 11 mRNAs, including Tmc5, Galnt6, Spedf, Mybl2, Muc5b, Six31, Pigr, Lamc2, Mmp13, Mal, and Mamdc2, and 11 novel piRNAs. Our data showed the interaction between piRNAs and mRNAs in OSCC, which might provide new insights in the development of diagnostic biomarkers and therapeutic targets of OSCC.

Research progress on the role and mechanism of miR-155 in the development of oral squamous cell carcinoma / 口腔疾病防治

@#Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Previous studies have found significantly high miR-155 expression in OSCC. However, the mechanism by which miR-155 plays a role in OSCC oncogenesis is not yet clear. This article reviews the function of the relationship between miR-155 and tumors and the potential role of miR-155 in the development of OSCC. A literature review showed that mir-155, as a small carcinogenic RNA, can inhibit CDC73, BCL6, P27Kip1 and other target genes that play a role in cancer inhibition; promote the proliferation, migration and invasion of OSCC cells; and inhibit apoptosis. miR-155 can also be combined with biological factors (Epstein-Barr virus, human papillomavirus) to promote the development of OSCC.