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OBJECTIVE: The aim of this study was to investigate whether microRNA-421 could participate in the proliferative, migratory and inflammatory changes of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis by targeting SPRY1. PATIENTS AND METHODS: The expressions of microRNA-421 and SPRY1 in synovial tissues and FLS were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The binding condition between microRNA-421 and SPRY1 was verified by the Dual-Luciferase reporter gene assay. MicroRNA-421 mimics and inhibitor were constructed and transfected. The levels of extracellular interleukin-1 (IL-1), IL-6, and COX2 in FLS after microRNA-421 mimics or inhibitor transfection were detected by enzyme-linked immunosorbent assay (ELISA). The regulatory effect of microRNA-421 on the proliferation and migration of FLS was detected using cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, collagen-induced RA mouse model was constructed to confirm the specific effect of microRNA-421 on regulating RA development. RESULTS: MicroRNA-421 was highly expressed in the synovial tissues of RA patients. SPRY1 expression in FLS was negatively regulated by microRNA-421. Moreover, the overexpression of microRNA-421 significantly promoted proliferative, invasive potentials and inflammatory response of FLS. In vivo, RA mouse model indicated that downregulated microRNA-421 and upregulated SPRY1 were observed in mice injected with cortisone and microRNA-421 inhibitor when compared with those of controls. CONCLUSIONS: MicroRNA-421 promotes the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by downregulating the SPRY1 expression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aim to investigate the expression of long non-coding RNALINP1 (lncRNA LINP1) in prostate cancer (PCa) and its potential mechanism. PATIENTS AND METHODS: The expression of lncRNA LINP1 in 74 pairs of PCa and normal tissues were detected by quantitative Real- time polymerase chain reaction (qRT-PCR); the relationship between its expression and the pathological features and prognosis of PCa was also analyzed. The expression of lncRNA LINP1 in the PCa cell line was verified by qRT-PCR. Knockdown of LINP1 was constructed by transfection of small interfering RNA (siRNA) in two PCa cell lines (Lncap and PC-3). The biological function of LINP1 was evaluated by cell counting kit-8 (CCK-8) assay, colony formation assay, migration and invasion assay, respectively. Finally, the potential mechanism of LINP1 was explored by Western blot and qRT-PCR. RESULTS: qRT-PCR results showed a higher expression of LINP1 in PCa than that of normal tissues. Compared with PCa patients with a lower expression of LINP1, those with higher expression had a higher tumor stage, lymphatic metastasis and distant metastasis rate, and lower overall survival rate. Proliferation, invasion and metastasis in cells transfected with si-LINP1 were remarkably decreased than those transfected with negative control (si-NC). Moreover, the expressions of the key proteins in the p53 signaling pathway, including p53, PTEN, Akt and CDK2 were remarkably decreased in cells after knockdown of LINP1. In addition, a negative correlation between LINP1 and p53 was confirmed by rescue experiments. CONCLUSIONS: Up-regulated LINP1 in PCa was correlated with a higher PCa stage, lymphatic metastasis, distant metastasis, and worse prognosis. Furthermore, LINP1 could promote the proliferative, migratory and invasive abilities of PCa by regulating the p53-signaling pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease, whereas its cause still remains elusive. Typical pathological manifestations of RA include persistent synovitis and bone degeneration in the surrounding joints. Although the incidence of RA is high in population, currently there have been no effective cures for it. The purpose of this study is to investigate the therapeutic effects and main mechanism of IKKε (inhibitor of nuclear factor kappa-B kinase ε) in collagen II induced-Rheumatoid Arthritis (CIA) mice model. MATERIALS AND METHODS: IKKε-/- and wild-type (WT) littermate control mice were intraperitoneally injected with 5 mg/kg collagen II monoclonal antibody cocktail (Cab) for 5 days. After that, the nociception threshold and clinical rheumatoid arthritis articular damage score of mice were evaluated. After 5 days-CAb treatment, serum levels of a series of inflammatory cytokines including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and interferon (IFN) were detected with enzyme-linked immunosorbent assay (ELISA) in both groups. Besides, Real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) was used to evaluate the expression of these inflammatory cytokines in plantar tissues. In addition, Western blot was performed to investigate the protein levels of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B) signaling pathway. Moreover, WT mice receiving CAb were further applied with or without IKK inhibitor amlexanox (25 mg/kg) to investigate the expression of the above-mentioned inflammatory cytokines. RESULTS: Our work showed that IKKε-/- mice with CIA displayed less nociception and suppressed inflammatory response than WT mice. Meanwhile, the clinical rheumatoid arthritis articular damage scores were significantly decreased in IKKε-/- mice. The levels of TNF-α, IL-1β, IL-6 in serum and plantar tissues in IKKε-/- mice were significantly lower than those in WT mice. Besides, NF-κB expression in IKKε-/- mice was significantly decreased. Similarly, the same phenotype was observed in WT mice administrated with IKKε inhibitor amlexanox as that of IKKε-/- mice, indicating that inflammatory and nociception responses were remarkably decreased than those of the negative controls. CONCLUSIONS: IKKε plays an important role in promoting nociception and inflammatory response in CIA. Our research demonstrated that knockout of IKKε may serve as a new direction for clinical prevention and treatment of rheumatoid arthritis. IKKε inhibitor amlexanox may become a new drug for the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Summary: The pine nematode Bursaphelenchus mucronatus has been associated with pine wilt in China. This work was intended to investigate the role of the pathogenicity‐related β‐1,4‐endoglucanase gene of B. mucronatus in the infection of pines. In this study, the full‐length cDNA of the Bm‐eng‐1 gene was cloned and characterized from a B. mucronatus isolate. Phylogenetic analysis suggested that the Bm‐eng‐1 gene of B. mucronatus may be acquired from fungi through horizontal gene transfer. The function of the gene was demonstrated using RNA interference. RNA interference indicated that Bm‐eng‐1 was involved in the dispersal, reproductive ability and pathogenicity of B. mucronatus. In situ hybridization showed that Bm‐eng‐1 was specifically expressed in the oesophageal gland of B. mucronatus. Furthermore, to investigate the relation between β‐1,4‐endoglucanase activities and virulence of different isolates, the β‐1,4‐endoglucanase activities and the expression levels of Bm‐eng‐1 were detected in six B. mucronatus isolates with different virulence. β‐1,4‐Endoglucanase activity was generally higher in pathogenic isolates than in non‐pathogenic isolates, and the Bm‐eng‐1 expression levels in different isolates were positively correlated with the β‐1,4‐endoglucanase activity. These findings suggested that β‐1,4‐endoglucanase plays important roles in the pathogenic process of B. mucronatus, and the differential expression of the gene may underlie the different activity levels of β‐1,4‐endoglucanase, subsequently influencing variations in virulence of B. mucronatus isolates. [ABSTRACT FROM AUTHOR]

The internal transcribed spacer ( ITS) regions of rDNA have been routinely employed for identification and phylogenetic analysis of many nematode species. In this study, the intra- and interspecies ITS genetic diversity of Bursaphelenchus xylophilus and Bursaphelenchus mucronatus was evaluated. Ninety-one isolates of the two nematode species collected from 14 Chinese provinces, Japan and Korea were used for ITS- PCR and sequencing. An unweighted pair group cluster analysis dendrogram clustered them as two B. mucronatus and one B. xylophilus independent clades. Principal component analysis showed the phylogenetic relationship of the two nematode species more clearly; B. mucronatus isolates were separated into more than four groups, whereas B. xylophilus isolates still clustered into a group. The results of the Mantel test indicated the correlation of genetic distance matrices and geographic distance matrices was significant for both nematode species. The genetic differentiation coefficient ( Gst) and gene flow ( Nm) of B. mucronatus were 0.341 and 1.091, respectively, suggesting the importance of landscape heterogeneity and considerable obstacles for genetic exchange among B. mucronatus isolates in China. However, Gst and Nm of B. xylophilus were 0.188 and 2.151, respectively, very different compared to B. mucronatus. This could be owing to the short-term introduction of B. xylophilus into China and a rapid spread through anthropogenic pathways. Our work adds to the understanding of the genetic diversity and genetic relationship of the two pine-parasitic nematode species, and will aid in controlling them in the future. [ABSTRACT FROM AUTHOR]

Dahuofang Reservoir is one of the most important water conservation projects supplying water to the cities of Shenyang and Fushun. Water quality security is the key to protecting the safety of water supply. To determine the current state of the water quality conditions in Hunhe River upstream of Dahuofang Reservoir, a seasonal analysis was conducted on the basis of the water quality monitoring data collected from three storage sections (Beizamu, Gulou, and Taigou) upstream of Dahuofang Reservoir from 2004 to 2012. The Kendall testing method for analysis of possible trends in pollutant concentration variation in the upstream portion of Dahuofang Reservoir was utilized. The results showed that (1) in all seasons and sections, the minimum total nitrogen concentration was 2.1 mg/L, a little greater than grade V water quality standard value 2 mg/L and is gradually increasing over recent years. Therefore, the primary source in need of pollution control is total nitrogen in Hunhe River upstream of Dahuofang Reservoir. (2) Concentrations of ammonia nitrogen and permanganate were 0.694 and 4.2 mg/L in Beizamu section during dry season, which exceeded 38.8% and 5% of grade II standard of National Surface Water Quality (NSWQ), respectively, well above that noted during wet and normal seasons and higher than that found in any other section. Therefore, the predominant pollution control sources are ammonia nitrogen and permanganate index at Beizamu section in dry season. (3) Five-day biochemical oxygen demand (BOD5) in Gulou section during wet season was 3.3 mg/L, which is more than 10% of grade II standard of NSWQ and greater than that of any other section and any other period. Thus, the predominant pollution originates from BOD5in Gulou section during wet season. (4) All pollution indices of Taigou section were found to be above grade II standard of NSWQ. [ABSTRACT FROM PUBLISHER]

OBJECTIVE: Intrauterine glucocorticoid (GC) exposure is associated with disturbances in feto-placental growth. This study aimed to investigate whether folic acid supplementation can prevent dexamethasone (Dex)-induced feto-placental growth restriction. MATERIALS AND METHODS: Female C57BL/6J mice were subject to four different treatments, respectively: normal drinking water plus saline injection (NN), normal drinking water plus Dex injection (ND), drinking water supplemented with folic acid plus saline injection (FN), and drinking water supplemented with folic acid plus Dex injection (FD). Folic acid (100 μg/L) was administrated since 2 weeks before the mating and throughout pregnancy. Dex injection (100 μg/kg·d) was performed from E12.5 to E16.5. The placentas were collected at E17.5. RESULTS: The parameters including placental and fetal weight, the maximum placental diameter, volume of junctional and labyrinthine zones, and vascular density in the ND group were significantly smaller compared to the NN group. Except the maximum placental diameter, each of the above parameters in the FD group was significantly larger compared to the ND group.The levels of glucocorticoid receptor (GR) protein, and endothelial growth factor A, C (VEGFA, VEGFC) and placental growth factor (PIGF) mRNAs were significantly lower in the ND group compared to NN group. The VEGFA and PIGF mRNA level in the FD group was significantly higher than that in the ND group, as well as VEGFA and VEGFC protein level. CONCLUSIONS: Folic acid may attenuate Dex-induced restriction on placental growth by elevating the expression of VEGFA and PIGF, and further raising vascular density. [ABSTRACT FROM AUTHOR]

Thymic stromal lymphopoietin (TSLP), an interleukin 7-like cytokine, can trigger dendritic cell (DC)-mediated T-helper type 2 (Th2) inflammatory responses. Recent evidence dem-onstrates that cytokines TSLP and 0X40 (CD134)/OX40 li-gand seem to be important players in the maintenance of Th2 memory pool in the pathogenesis of asthma. Accumu-lating data reveal that the pathogenic T cells involved in asthma are likely to be inflammatory Th2 cells. TSLP is in-volved in the development of asthma through crosstalk with nuclear factor NF-KB. Progression of skin fibrosis in atopic dermatitis occurs via TSLP/TSLP receptor. TSLP-mediated dermal inflammation aggravates experimental allergic asth-ma. Also, TSLP polymorphisms are associated with suscepti-bility to asthma, atopic dermatitis, and eczema herpeticum. These findings suggest a master switch of TSLP in the initia-tion of allergic and adaptive inflammation through innate pathways at the epithelial cell-DC interface. The TSLP path-way is therefore a promising target for immunotherapy of allergic diseases. [ABSTRACT FROM AUTHOR]

The mechanism underlying late-phase allergic reactions (LPR) remains incompletely understood. This study aimed to investigate the role of a newly described subset of T cells, interleukin (IL)-9 IL-10 T cells, in the pathogenesis of LPR. Using a T helper type 2 (Th2) inflammatory mouse model, we examined the frequency of IL-9 IL-10 T cells in the jejunum by immunohistochemistry. The LPR in the jejunum was observed afterwards. The cytokine profile of IL-9 IL-10 T cells was characterized and the major cytokine that plays the critical role in the initiation of LPR was investigated. Abundant IL-9 IL-10 T cells as well as inflammatory cell extravasation in the jejunal sections were observed in sensitized mice 48 h after specific antigen challenge. IL-9 IL-10 T cells expressed high levels of macrophage inflammatory protein 1 (MIP1) that could be enhanced by T cell receptor activation. MIP1 facilitated macrophage extravasation in local tissue. Macrophage-derived MIP2 contributed to neutrophil infiltration in the intestine in LPR. Pretreatment with anti-MIP antibody inhibited the LPR in the intestine. IL-9 IL-10 T cells play an important role in LPR. This subset of T cells has the potential to be a novel therapeutic target in the treatment of LPR and LPR-related inflammation. [ABSTRACT FROM AUTHOR]

Background: Nuclear factor κB (NF-κB) overactivation plays a crucial role in T-helper 2 (Th2)-biased allergic airway inflammation by increased activation and decreased apoptosis of CD4+ T cells. We have shown that targeted NF-κB suppression in dendritic cells by adenoviral gene transfer of a novel mutated inhibitor of NF-κB (IκBα) (AdIκBαM) contributes to T-cell tolerance, but the immunosuppressive action of AdIκBαM on memory (CD45RO+) CD4+ T cells remains enigmatic. Methods: CD45RO+ T cells from Dermatophagoides farinaei-sensitized asthmatic patients, untransfected or transfected with AdIκBαM or AdLacZ (β-galactosidase) for 24 h, were stimulated with anti-CD3 (1.0 μg/ml) plus anti-CD28 (0.5 μg/ml) monoclonal antibody for an additional 24 h. IκBαM transgene expression and NF-κB activation were detected by polymerase chain reaction (PCR), reverse transcription-PCR (RT-PCR), Western blot analysis, and electrophoretic mobility shift assay. Phenotype and apoptosis were measured by flow cytometry, annexin V binding, and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling analyses. Cytokine production and cell proliferation were determined using enzyme-linked immunosorbent assay and [3H] thymidine incorporation. Results: A unique 801-bp IκBαM cDNA and a dose-dependent increase in IκBαM transgene expression were observed in AdIκBαM-transfected CD45RO+ T cells. Significantly, AdIκBαM inhibited CD3/CD28-mediated NF-κB activation in CD45RO+ T cells, leading to evident apoptosis, reduction of eotaxin, RANTES, Th1 [interferon (IFN)-γ and interleukin (IL)-2], and Th2 (IL-4, IL-5, and IL-13 despite a slight decrease in IL-10) cytokines and secondary proliferative response. AdIκBαM also upregulated cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and downregulated CD69 besides no change in CD28. Conclusion: IκBαM might be beneficial to augment memory CD4+ T-cell tolerance through modulating B7-CD28/CTLA-4 co-stimulatory pathways and NF-κB-dependent cytokine profiles in allergic inflammatory diseases including asthma. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Long non-coding RNA LINP1 promotes the malignant progression of prostate cancer by regulating p53" by H.-F. Wu and others which appeared in the 2018 issue.