Cadmium exposure triggers oxidative stress, necroptosis, Th1/Th2 imbalance and promotes inflammation through the TNF-α/NF-κB pathway in swine small intestine.

Cadmium (Cd) is a toxic environmental pollutant and induces toxic effects to organism. Nevertheless, the mechanism of Cd-induced toxicity in swine remains obscure. To explore this, 10 healthy 6-week-old weaned swine were placed into two groups stochastically, the Cd group was treated with a commercial diet containing 20 mg/kg Cd for 40 days. The results of histopathological and ultrastructural observations showed typical necrosis features and inflammatory cell infiltration in Cd group. Excessive Cd suppressed T-AOC and SOD activities, increased MDA content and ROS levels. Cd diet elevated the expression of RIPK1, RIPK3, and MLKL to activate the RIPK3-dependent necroptosis pathway. Results of Th1 and Th2 cytokines indicated that the levels of IL-4, IL-6 and IL10 was increased, while the level of IFN-γ was decreased, illustrating Th1/Th2 immune imbalance leads to aggravate inflammatory responses. Cd activated the TNF-α/NF-κB pathway and induced inflammatory responses via increasing the expression of HO-1, IL-1ß, iNOS, COX2. Heat shock proteins were notably elevated in response to inflammatory reactions. And these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC). Altogether, these data demonstrated that Cd induced necroptosis and inflammation to aggravate small intestine injury in swine by increasing the excessive accumulation of ROS and imbalanced Th1/Th2, respectively.

ln RNA LINC01234 promotes triple-negative breast cancer progression through regulating the miR-429/SYNJ1 axis.

Emerging evidence has illustrated that long noncoding RNA 01234 (LINC01234) has played a pivotal role in the development and progression of human cancer. The regulatory role and underlying mechanisms of LINC01234 in triple-negative breast cancer (TNBC) remains unknown. In this study, we analyzed the expression level of LINC01234 in several breast cancer cell lines. CCK-8, EdU, flow cytometry analysis, wound healing assay, and transwell assay were carried out to investigate the effect of LINC01234 on tumor proliferation, apoptosis, and migration. Bioinformatic analysis and luciferase reporter assays were performed to confirm the molecular binding. We found that LINC01234 was dramatically upregulated in breast cancer cell lines, especially in TNBC. The loss and gain-of functional experiments revealed that LINC01234 significantly promoted proliferation, migration, and suppressed cell apoptosis of MDA-MB-231 cells in vitro and inhibited tumorigenesis in vivo. Mechanistic investigations demonstrated that LINC01234 might act as a competing endogenous RNA (ceRNA) for miR-429 to regulate the SYNJ1 expression. The effects of miR-429 and SYNJ1 in MDA-MB-231 cells were also analyzed. Our results revealed that the novel LINC01234/miR-429/SYNJ1 axis played a critical role in progression of TNBC cell line MDA-MB-231, and it may serve as a therapeutic target for TNBC.

Potential of RASSF1A promoter methylation as a biomarker for colorectal cancer: Meta-analysis and TCGA analysis.

The RAS association domain family protein 1A (RASSF1A) is a tumor suppressor in colorectal cancer (CRC), and is often inactived by hypermethylation. Therefore, we evaluated the association between RASSF1A hypermethylation and the risk and prognosis in CRC. We identified literature through searching PubMed and China National Knowledge Infrastructure databases, and then validated and supplemented the meta-analysis with TCGA analysis. Twenty-three studies involving 2886 subjects of CRC were examined. The meta-analysis showed that RASSF1A promoter methylation inferred high CRC risk (odds ratio, 6.53, 95% confidence interval 3.88-11.01, P < .001) and poor overall survival (hazard ratio 2.85, 95% CI 1.88-4.31, P < .001). The TCGA analysis suggested that effect of RASSF1A promotor methylation was affected by tumor localization (colon vs. rectum). RASSF1A promoter methylation was a predictor of high risk (OR 2.38, 95%CI 1.02-5.6, P = .046) and poor disease free survival(HR 2.25, 95%CI 1.27-3.99, P = .006)in colon adenocarcinoma, but the association was statistically insignificant in rectum adenocarcinoma(HR 1.58, 95% CI 0.69-3.59, P = .28). These results suggested RASSF1A hypermethylation is a risk and a potential prognostic biomarker in CRC.

miR-148b-3p, miR-190b, and miR-429 Regulate Cell Progression and Act as Potential Biomarkers for Breast Cancer.

PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.

Effect of phosphorus deficiency on erythrocytic morphology and function in cows.

The aim of this study was to evaluate the influence of phosphorus (P) deficiency on the morphological and functional characteristics of erythrocytes in cows. Forty Holstein-Friesian dairy cows in mid-lactation were randomly divided into two groups of 20 each and were fed either a low-P diet (0.03% P/kg dry matter [DM]) or a control diet (0.36% P/kg DM). Red blood cell (RBC) indices results showed RBC and mean corpuscular hemoglobin decreased while mean corpuscular volume increased significantly (p ＜ 0.05) in P-deficient cows. Erythrocyte morphology showed erythrocyte destruction in P-deficient cows. Erythrocytes' functional characteristics results showed total bilirubin and indirect bilirubin concentrations and aspartate transaminase and alanine transaminase activity levels in the serum of P-deficient cows were significantly higher than those in control diet-fed cows. Activities of superoxide dismutase and glutathione peroxidase in erythrocytes were lower, while the malondialdehyde content was greater, in P-deficient cows than in control diet-fed cows. Na+/K+-ATPase and Mg2+-ATPase activities were lower in P-deficient cows than in control diet-fed cows; however, Ca2+-ATPase activity was not significantly different. The phospholipid composition of the erythrocyte membrane changed and membrane fluidity rigidified in P-deficient cows. The results indicate that P deficiency might impair erythrocyte integrity and functional characteristics in cows.

Meta-analysis of the correlation between selenium and incidence of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common cancer type. There is a correlation between selenium (Se) deficiency and the incidence of HCC. To clarify the effects of Se level on the risk of HCC patients, a meta-analysis was performed. A total of 9 articles published between 1994 and 2016 worldwide were selected through searching PubMed, EMBASE, web of science, Cochrane Library, Springer Link, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM), and the information were analyzed using a meta-analysis method. Heterogeneity was assessed by using the I2 index. Publication bias was evaluated by Begg's Test analysis. Pooled analysis indicated that patients with HCC had lower Se levels than the healthy controls [standardized mean difference (SMD)= -1.08, 95% confidence intercal (CI) = (-0.136, -0.08), P < 0.001]. Further subgroup analysis showed this effect to be independent of the study design, race or sample collection. In conclusion, this meta-analysis suggested an inverse correlation between Se level and the risk of HCC in humans patients.

Effect of cold stress on expression of AMPKalpha-PPARalpha pathway and inflammation genes.

Animals are exposed to various environmental stresses every day, including the stress associated with living in cold temperatures. The aim of this study was to investigate the possible mechanisms of interaction between lipid metabolism and inflammation induced by cold stress in the livers of chickens. Fifteen-day-old male chicks were randomly allocated into 12 groups (10 chickens per group). After exposure of the chickens to the cold stress, cholesterol fractionation was used to examine high-density lipoprotein (HDL) and low-density lipoprotein (LDL) concentrations. Aminotransferase activities were examined with the use of the aspartate transaminase (AST) and alanine transaminase (ALT) assay. The AMP-activated protein kinase alpha-proliferator-activated receptor alpha (AMPKalpha-PPARalpha) pathway genes (AMPKalpha1, AMPKalpha2, PPARalpha, carnitine palmitoyltransferaseI [CPTI], acetyl-CoA carboxylase [ACC]) and inflammatory cytokines (prostaglandin E synthase [PGEs], inducible nitric oxide synthase [iNOS], heme oxygenase-1 [HO-1], nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kappaB], cyclooxygenase-2 [COX-2], and TNF-alpha-like factor [LITAF]) were also measured. The results showed that during the response to cold stress, serum LDL and HDL cholesterol concentrations increased. Histopathologic analyses provided evidence that liver tissues were seriously injured in the chickens exposed to the cold stress. Serum aminotransferase activities were also increased in the group of animals exposed to the cold stress. Additionally, the expressions of AMPKalpha-PPARalpha pathway genes and inflammatory cytokine genes were significantly increased in the animals exposed to cold temperatures. These results suggested that increased inflammation was a feature associated with a lipid-metabolism disorder in the livers of chickens exposed to cold stress.