Nano-periodic metallic grating structures are novel components that have several extraordinary optical transmission phenomena, such as surface plasmon polariton (SPP). In this work, we proposed a new efficient method based on the modified Neumann-to-Dirichlet (NtD) map to calculate the scattered fields from the nano-periodic metallic grating structures. In each sud-domain from the periodic metallic gratings, we construct the modified NtD map operators by boudary integral equations. The new operators avoid the numerical instability of the condition numbers from the challenging metallic materials with complex refractive index. Numerical result demonstrates that the new method achieves high accuracy for metallic diffraction gratings and indicates the phenomenon of surface plasmon polariton.
This study was performed to explain the underlying role of IL35 on the prognosis of patients with HCC.The expression of IL35 at the protein level was detected with immunohistochemistry (IHC). Chi-square test was performed to analyze the relationship between IL35 expression and clinical parameters of HCC patients. The correlation between expression level of IL35 and the prognosis of patients with HCC was evaluated by Kaplan-Meier method and Cox regression method.The positive rate of IL35 expression in HCC samples was about 62.7%, which was significantly higher than that in paired normal specimens (12%). The analyses suggested that there was no correlation between IL35 expression and age, gender, and tumor size (P>0.05), but a tight relationship was found between IL35 expression and metastasis, AFP, HBV infection, Child-Pugh (P<0.05). Susequent Kaplan-Meier analysis result indicated that positive expression of IL35 induced low survival rate of HCC patients, and the Cox regression analysis suggested that IL35 might be a biomarker for prognosis of patients with HCC.Generally, results of this study demonstrated that expression of IL35 shared a close association with the prognosis of patients with HCC. Therefore, IL35 could be considered as a novel index for prognosis of patients with HCC.
Acute gastric lesions induced by stress are frequent occurrences in medical establishments. The gastric dramatic downrelated gene (GDDR) is a secreted protein, which is abundantly expressed in normal gastric epithelia and is significantly decreased in gastric cancer. In our previous study, it was found that GDDR aggravated stress‑induced acute gastric lesions. However, the role of GDDR in acute gastric lesions remains to be fully elucidated. In the present study, RNA sequencing was performed in order to examine the gene expression profile regulated by GDDR in acute gastric lesions. The dataset comprised four stomach samples from wild-type (WT) mice and four stomach samples from GDDR‑knockout mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the differentially-expressed genes (DEGs). Weighted correlation network analysis was used to identify clusters of highly correlated genes. Cytoscape was used to construct a protein‑protein interaction network (PPI) of the DEGs. Based on the GO analysis, the upregulated DEGs were distinctly enriched in muscle contraction and response to wounding; and the downregulated DEGs were significantly enriched in the regulation of nitrogen compound metabolic process and regulation of RNA metabolic process. The results of the KEGG pathway analysis showed that the upregulated DEGs were enriched in ECM‑receptor interaction and the signaling pathway of cGMP‑PKG, and the downregulated DEGs were enriched in the renin‑angiotensin system and glycerolipid metabolism. The co‑expression network revealed a group of genes, which were associated with increased wound healing in the WT mice. Significant pathways were identified through the PPI network, including negative regulation of the signaling pathway of glucocorticoid receptor, regulation of cellular stress response, and regulation of hormone secretion. In conclusion, the present study improves current understanding of the molecular mechanism underlying acute gastric lesions and may assist in the treatment of gastric lesions.
Transforming growth factor-β (TGFβ) is crucial for liver fibrogenesis and the blunting of TGFβ signalling in hepatic stellate cells (HSCs) or hepatocytes can effectively inhibit liver fibrosis. microRNAs (miRNAs) have emerged as key regulators in modulating TGFβ signalling and liver fibrogenesis. However, the regulation of TGFβ receptor I (TβRI) production by miRNA remains poorly understood. Here we demonstrate that the miR-101 family members act as suppressors of TGFβ signalling by targeting TβRI and its transcriptional activator Kruppel-like factor 6 (KLF6) during liver fibrogenesis. Using a mouse model of carbon tetrachloride (CCl4 )-induced liver fibrosis, we conducted a time-course experiment and observed significant down-regulation of miR-101 in the fibrotic liver as well as in the activated HSCs and injured hepatocytes in the process of liver fibrosis. Meanwhile, up-regulation of TβRI/KLF6 was observed in the fibrotic liver. Subsequent investigations validated that TβRI and KLF6 were direct targets of miR-101. Lentivirus-mediated ectopic expression of miR-101 in liver greatly reduced CCl4 -induced liver fibrosis, whereas intravenous administration of antisense miR-101 oligonucleotides aggravated hepatic fibrogenesis. Mechanistic studies revealed that miR-101 inhibited profibrogenic TGFβ signalling by suppressing TβRI expression in both HSCs and hepatocytes. Additionally, miR-101 promoted the reversal of activated HSCs to a quiescent state, as indicated by suppression of proliferation and migration, loss of activation markers and gain of quiescent HSC-specific markers. In hepatocytes, miR-101 attenuated profibrogenic TGFβ signalling and suppressed the consequent up-regulation of profibrogenic cytokines, as well as TGFβ-induced hepatocyte apoptosis and the inhibition of cell proliferation. The pleiotropic roles of miR-101 in hepatic fibrogenesis suggest that it could be a potential therapeutic target for liver fibrosis.
Anti-tumor necrosis factor (TNF)-α therapeutics has the potential to alleviate allergic inflammation. However, in previous studies, the systemic administration of anti-TNF-α agents was frequently accompanied by many adverse effects, such as infection, immunogenicity and malignancy. Efforts are made in the present study to evaluate whether or not local administration of TNF-α antisense oligonucleotide would inhibit allergic airway inflammation and influence systemic immune responses in an ovalbumin-induced asthmatic murine model.The treatment effects of TNF-α antisense oligonucleotide on mice, as well as the alternative proportion of regulatory T cells and T(H) 2 cells, were examined and compared with untreated mice.Local administration of TNF-α antisense oligonucleotide resulted in significantly inhibited TNF-α expression, remarkably decreased inflammatory cell infiltration and dramatically reduced mucus hypersecretion. These treatment effects were associated with induced CD4(+) CD25(+) Foxp3(+) regulatory T cells, reduced T(H) 2 cells and generally decreased T(H) 2-type cytokines expression in bronchoalveolar lavage fluid. Systemic immunosuppression was not triggered by local antisense oligonucleotide administration because the proportion of CD4(+) CD25(+) Foxp3(+) regulatory T cells in the blood, thymus or spleen was not affected. Attenuated 4-1BBL expression was likely involved in the alternative proportion of T cells.These findings demonstrate that local administration of TNF-α antisense oligonucleotide contributes to anti-inflammatory action via the enhancement of regulatory T cells-mediated immune tolerance, which is not accompanied by systemic immunosuppression associated with systemically-induced regulatory T cells.
Although emerging evidence has indicated that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are associated with susceptibility to gastric cancer, a limited number of studies have revealed the underlying molecular mechanisms. In the present study, the results suggested that miR-1269a rs73239138 has a role in decreasing the risk of gastric cancer. The level of miR-1269a variant expression was significantly downregulated compared with the wild-type miR-1269a in the gastric cells (Fig. 1). Furthermore, overexpression of miR-1269a inhibited apoptosis of gastric cancer cells. Expression of the miR-1269a variant inhibited the function of miR-1269a by increasing the apoptotic rate and the expression of Bik, Bim and Bak was upregulated consistently. In addition, zinc-finger protein 70 (ZNF70) was identified to be a target gene of miR-1269a, which was downregulated by miR-1269a and upregulated by miR-1269a variant. ZNF70 was indicated to exert a role as a tumor suppressor in gastric cancer. To the best our knowledge, the present study for the first time highlights a critical role of miR-1269a variant rs73239138 in decreasing the susceptibility to gastric cancer by downregulating its expression and targeting ZNF70, which promotes apoptosis of gastric cancer cells. This SNP is indicated to serve as a potential biomarker and therapeutic target for gastric cancer.
Lipoprotein ratios have been shown to be associated with the occurrence of coronary heart disease (CHD), but little is known about their relationships with the severity of CHD. A total of 792 angiographically defined CHD patients were enrolled following their admission. Patients were stratified into three groups based on the tertile of the Gensini scores (≤33rd percentile, 33rd to 66th percentile and ≥66th percentile) or the number of stenotic coronary branches (single-branch stenosis, double-branch stenosis and multi-branch stenosis). Demographic and biochemical data were collected and lipoprotein ratios were calculated. Logistic regression and path analysis were employed to examine the relationships between the lipoprotein ratios and the severity of CHD. The ratios of low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B100 (apoB100)/apolipoprotein AI (apoAI) increased with the tertile of the Gensini scores (P < 0.05 for both). The ratios of triglyceride (TG)/HDL-C, total cholesterol (TC)/HDL-C, LDL-C/HDL-C and apoB100/apoAI increased with the number of stenotic coronary branches (P < 0.05 for all). The univariate logistic regression showed that the ratios of TC/HDL-C, LDL-C/HDL-C and apoB100/apoAI were positively associated with both the tertile of the Gensini scores and the number of stenotic vessels (P < 0.05 for all), and the ratio of TG/HDL-C was positively associated with the number of stenotic vessels (P < 0.05). In multivariate logistic analysis, only the ratio of apoB100/apoAI was independently and positively associated with the tertile of the Gensini scores (OR = 2.93, 95 % CI = 1.17-7.34, P = 0.022) and the number of stenotic vessels (OR = 3.14, 95 % CI = 1.01-6.47, P = 0.048) after adjusting for the possible confounding variables. The apoB100/apoAI ratio was also shown to be a direct mediator between the risk factors including age, BMI, HDL-C, LDL-C, apoB100 and apoAI and the severity of CHD by path analysis. Our data indicate that the apoB100/apoAI ratio could be a useful predictor for evaluating the severity of coronary stenosis in CHD patients.
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