ObjectiveIgG4-related disease (IgG4-RD) is a chronic systemic disease involved in many organs and tissues. As only limited autoantigens have been found since the beginning of this century, the aim of this study was to reveal new candidate autoantigens of IgG4-RD.MethodsMultiple cell lines including HT-29, EA.hy926, HEK 293 and HepG2 were used to test the binding ability of circulating autoantibodies from IgG4-RD sera. The amino-acid sequence was then analyzed by matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF) mass spectrometry. After the cloning and expression of recombinant putative autoantigen in a bacterial expression system, the corresponding immuno assay was set up and utilized to observe the prevalence of serum autoantibodies in a large set of confirmed clinical samples.ResultsOne positive autoantigen was identified as prohibitin. ELISA analysis showed that a majority of patients with IgG4-RD have antibodies against prohibitin. Anti-prohibitin antibodies were present in the sera of patients with definite autoimmune pancreatitis (25/34; 73.5%), Mikulicz’s disease (8/15; 53.3%), retroperitoneal fibrosis (6/11; 54.5%), other probable IgG4-RD (26/29; 89.7%) and Sjögren’s syndrome (4/30; 13.3%) but not in apparently healthy donors (1/70; 1.4%).ConclusionsAn association between prohibitin and patients with some IgG4-RD was observed, although the results were quite heterogeneous among different individuals within autoimmune pancreatitis, Mikulicz’s disease and retroperitoneal fibrosis.

Background The transition of right ventricle (RV) from a compensated to decompensated state contributes to survival in pulmonary arterial hypertension (PAH). This study investigates the significance of right atrial (RA) dysfunction on disease progression in PAH. Methods Eighty patients with PAH, including 58 with hemodynamically compensated RV function (PAH-C) and 22 with decompensated RV function (PAH-D), were compared with 80 age-matched and sex-matched normal controls. RA longitudinal strain and strain rate (SR) parameters corresponding to reservoir (total strain ε s and strain rate SR s ), conduit (passive strain ε e and strain rate SR e ), and booster pump (active strain ε a and strain rate SR a ) phases were derived by a rapid semiautomated method on cine cardiovascular magnetic resonance. Results In PAH compared with controls, significantly reduced RA strains and SRs were observed. Among patients with PAH, PAH-D had significantly impaired RA strains and SRs compared with PAH-C. RA total strain and passive strain were the best parameters for differentiating PAH-D from PAH-C. Lower RA strain correlated with increased RA pressure ( r =−0.57; P <0.0001), RV volume ( r =−0.37; P =0.002) and biomarker ( r =−0.53; P <0.0001), impaired RV function ( r =0.46–0.72; P <0.0001), and lower exercise capacity ( r =0.41; P <0.0001). Reduced RA strains were significantly associated with higher risk of clinical worsening in PAH. RA passive strain was the best predictor of a composite adverse event end point (Harrell’s C statistic,0.75; hazard ratio,0.84; P =0.019) compared with other conventional RA and RV functional measurements. Conclusions RA phasic functions are impaired in PAH. Among patients with PAH, impaired RA strains reflect RV decompensation and higher risks and predict adverse clinical outcomes. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT02790918.

Colorectal neoplasia differentially expressed (CRNDE) is a long non-coding RNA which has been proved upregulated in various cancers. Meanwhile, CRNDE has been demonstrated to be involved in multiple biological processes of different cancers according to previous study. Moreover, recent studies suggested CRNDE might be a potential diagnostic biomarker and prognostic predictor due to its high sensitivity and specificity in cancer tissues and plasma. In this review, we summarize the biological function of CRNDE and the relevant mechanisms in cancers to establish a molecular basis for the clinical use of CRNDE in the future.

MicroRNAs are small nonprotein-encoding RNAs ranging from 18 to 25 nucleotides in size and regulate multiple biological pathways via directly targeting a variety of associated genes in cancers. MicroRNA-27b is a highly conserved MicroRNA throughout vertebrates and there are two homologs (hsa-miR-27a and hsa-miR-27b) in humans. MicroRNA27b is an intragenic microRNA located on chromosome 9q22.1 within the C9orf3 gene, clustering with miR-23b and miR-24-1 in human. As a frequently dysregulated microRNA in human cancers, microRNA-27b could function as a tumor suppressor or an oncogenic microRNA. More and more studies indicate that microRNA-27b is involved in affecting various biological processes, such as angiogenesis, proliferation, metastasis, and drug resistance, and thus may act as a promising therapeutic target in human cancers. In this review, we discuss the role of microRNA-27b in detail and offer novel insights into molecular targeting therapy for cancers.

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed the invasion and metastasis of PDAC. However, the function of YY1 on proliferation and migration of pancreatic cancer remains to be clarified. In this study, we found that YY1 overexpression or knockdown can inhibit or promote the proliferation and migration of pancreatic cancer cells. Digital gene expression sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the candidate target gene of YY1. Then we found that YY1 can downregulate the expression of CDKN3 by directly binding to the promoter region of CDKN3. Silencing CDKN3 expression could inhibit the ability of cell proliferation and migration and overexpression of CDKN3 could restore the effects induced by YY1 overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3 were negatively correlated in pancreatic cancer tissues and PDAC patients with higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3 can form a complex with MdM2-P53, thus leading to inhibiting the expression of P21, which is the target gene of P53, and finally facilitates the cell cycle to promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly regulate the expression of CDKN3 and participate in the cycle of pancreatic cancer cells, which can inhibit the progression of pancreatic cancer. These results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic tumorigenesis, which may develop new methods for human pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) is a gastrointestinal malignancy with a dismal clinical outcome. Accumulating evidence suggests that activated pancreatic stellate cells (PSCs), the major producers of extracellular matrix (ECM), drive the severe stromal/desmoplastic reaction in PDAC. Furthermore, the crosstalk among PSCs, pancreatic cancer cells (PCCs) as well as other stroma cells can establish a growth-supportive tumor microenvironment (TME) of PDAC, thereby enhancing tumor growth, metastasis, and chemoresistance via various pathways. Recently, targeting stroma has emerged as a promising strategy for PDAC therapy, and several novel strategies have been proposed. The aim of our study is to give a profound review of the role of PSCs in PDAC progression and recent advances in stroma-targeting strategies.

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ERx/HER2x phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA A ) receptor subunit p (GABAp, GABRP) in some breast cancers with ERx/HER2x phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABAp gene expression in a separate cohort of 121 invasive breast cancers. GABAp gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABAp gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ERx/HER2x phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABAp in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABAp gene expression was associated with ERx/HER2x phenotype (P<0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (£ 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABAp gene expression was also associated with combinations of high grade with ERx/HER2x phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABAp gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

IR and hyperglycemia were positively correlated with the flow patterns, RI, and VI of thyroid nodules, especially in large nodules. The findings suggest a pivotal role of IR in the distribution, construction, and density of thyroid nodular vascularization, which might contribute to the growth and the progression of thyroid nodules.