Proteomics identifies a novel role of fibrinogen-like protein 1 in Crohn's disease.

BACKGROUND: Crohn's disease (CD) is an incurable intestinal disorder with unclear etiology and pathogenesis. Currently, there is a lack of specific biomarkers and drug targets for CD in clinical practice. It is essential to identify the precise pathophysiological mechanism of CD and investigate new therapeutic targets. AIM: To explore a new biomarker and therapeutic target for CD and verify its role in the CD pathological mechanism. METHODS: Proteomics was performed to quantify the protein profile in the plasma of 20 CD patients and 20 matched healthy controls. Hub genes among the selected differentially expressed proteins (DEPs) were detected via the MCODE plugin in Cytoscape software. The expression level of one hub gene with an immunoregulatory role that interested us was verified in the inflamed intestinal tissues of 20 CD patients by immunohistochemical analysis. After that, the effects of the selected hub gene on the intestinal inflammation of CD were identified in a CD cell model by examining the levels of proinflammatory cytokines by enzyme-linked immunosorbent assays and the expression of the NF-κB signalling pathway by quantitative real-time PCR analysis and Western blot assays. RESULTS: Thirty-five DEPs were selected from 393 credible proteins identified by proteomic analysis. Among the DEPs, fibrinogen-like protein 1 (FGL1), which attracted our attention due to its function in the regulation of the immune response, had 1.722-fold higher expression in the plasma of CD patients and was identified as a hub gene by MCODE. Furthermore, the expression of FGL1 in the intestinal mucosal and epithelial tissues of CD patients was also upregulated (P < 0.05). In vitro, the mRNA levels of FGL1 and NF-κB; the protein expression levels of FGL1, IKKα, IKKß, p-IKKα/ß, p-IκBα, and p-p65; and the concentrations of the proinflammatory cytokines IL-1ß, IL-6, IL-17, and TNF-α were increased (P < 0.05) after stimulation with lipopolysaccharide, which were reversed by knockdown of FGL1 with siRNA transfection (P < 0.05). Conversely, FGL1 overexpression enhanced the abovementioned results (P < 0.05). CONCLUSION: FGL1 can induce intestinal inflammation by activating the canonical NF-κB signalling pathway, and it may be considered a potential biomarker and therapeutic target for CD.

Magnetic resonance imaging findings for differential diagnosis of perianal plexiform schwannoma: Case report and review of the literature.

Plexiform schwannoma is an extremely rare variant of schwannoma, accounting for approximately 5% of cases. Due to the rarity and lack of typical symptoms, signs and radiological images, a definite diagnosis of plexiform schwannoma may not be made by clinicians prior to biopsy. In the present study, we report the first case (to our knowledge) of perianal plexiform schwannoma arising from the overlapped skin of the ischioanal fossa, and we propose an intratumorally nonenhanced circumferential capsule dividing the tumour into multiple homogeneously enhanced nodules as a magnetic resonance imaging feature to aid in the differential diagnosis of plexiform schwannoma from ancient schwannoma, cavernous haemangioma, liposarcoma and plexiform neurofibroma.

The Aqueous Fraction of Areca catechu Nut Ameliorates Demyelination in Prefrontal Cortex-Induced Depressive Symptoms and Cognitive Decline through Brain-Derived Neurotrophic Factor-Cyclic Adenosine Monophosphate Response Element-Binding Activation.

OBJECTIVE: To investigate if Areca catechu L. treatment could ameliorate depressive symptoms and cognitive decline by facilitating myelination processes in prefrontal cortex. METHODS: A mouse model of cuprizoneinduced demyelination was used to mimic demyelinating disease. Two concentrations of A. catechu nut extract (ANE; 1% and 2%) were administered orally in the diet for 8 weeks. Depressive symptoms and cognition-associated behaviors were evaluated in tests of locomotor activity, tail suspension, and forced swimming; spatial memory was tested with the Y-maze. Expression of myelin basic protein (MBP), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), glutathione S-transferases pi (GSTpi), brain-derived neurotrophic factor (BDNF), and the transcription factor cyclic adenosine monophosphate (cAMP) response element-binding (CREB) were evaluated by western blot. RESULTS: Animals subjected to demyelination showed hyperactivity (P<0.01), impaired spatial memory (P<0.01), and depressive behaviors (P<0.05). Internally, they displayed signifificant myelin damage in the cortex, lower expression of CNPase and GSTpi, slightly decreased BDNF (P>0.05), and signifificantly reduced p-CREB (P<0.05). Nevertheless, ANE treatment demonstrated signifificant anti-depressant activity and enhancement of working memory (P<0.05 or 0.01). In addition, ANE treatment increased MBP, CNPase and GSTpi protein expression in prefrontal cortex (P<0.05). Concomitant with increased BDNF production (P<0.05), ANE treatment up-regulated phosphorylated CREB, but without statistical signifificance (P>0.05). CONCLUSION: ANE treatment might ameliorate depressive symptoms and cognitive decline by facilitating myelination processes in prefrontal cortex via induction of BDNF-CREB activation.

Visualization of miniSOG Tagged DNA Repair Proteins in Combination with Electron Spectroscopic Imaging (ESI).

The limits to optical resolution and the challenge of identifying specific protein populations in transmission electron microscopy have been obstacles in cell biology. Many phenomena cannot be explained by in vitro analysis in simplified systems and need additional structural information in situ, particularly in the range between 1 nm and 0.1 µm, in order to be fully understood. Here, electron spectroscopic imaging, a transmission electron microscopy technique that allows simultaneous mapping of the distribution of proteins and nucleic acids, and an expression tag, miniSOG, are combined to study the structure and organization of DNA double-strand break repair foci.

Germline mutations in BAP1 impair its function in DNA double-strand break repair.

The BRCA1-associated deubiquitylase BAP1 is mutated in several cancers, most notably mesothelioma and melanoma, where it is thought to promote oncogenesis. In this study, we present evidence that BAP1 functions as part of the DNA damage response (DDR). We found that BAP1 mediates rapid poly(ADP-ribose)-dependent recruitment of the polycomb deubiquitylase complex PR-DUB to sites of DNA damage. Furthermore, we identified BAP1 as a phosphorylation target for the DDR kinase ATM. Functionally, BAP1 promoted repair of DNA double-strand breaks, enhancing cell survival after DNA damage. Our results highlight the importance of ubiquitin turnover at sites of DNA damage, and they provide a mechanism to account for the tumor-suppressive function of BAP1.