Concentrations, distribution, and key influencing factors of antibiotic resistance genes and bacterial community in water and reared fish tissues in a typical tilapia farm in South China.

Although previous studies have investigated the occurrence of antibiotic resistance genes (ARGs) in aquaculture, few have monitored the concentrations and propagation of ARGs in biological tissues or investigated the key factors influencing their spread in aquaculture. This study investigated the concentration, propagation, and distribution of ARGs and bacterial communities in water sources, pond water, and tilapia tissues, and their key influencing factors, in a typical tilapia farm. ErmF, sul1, and sul2 were the dominant ARGs with high concentrations. The total concentrations of ARGs (TCAs) in tilapia tissues decreased in the following order: stomach > scales > intestine > gills (P < 0.05). Redundancy analysis and multiple linear regression revealed that suspended solids (SS) and chemical oxygen demand (COD) were positively correlated with the dominant ARGs ermF sul2, and the TCAs (P < 0.05); additionally, Chloroflexi and Bacteroidetes in tilapia aquaculture water were positively correlated with the dominant ARGs ermF and sul2, as well as the TCAs (P < 0.05). This study suggests that SS and COD were the key factors driving the distribution and spread of ARGs in tilapia aquaculture water. Additionally, Chloroflexi and Bacteroidetes were the key bacterial flora affecting the propagation of ARGs in tilapia aquaculture systems.

Downregulation of ACC expression suppresses cell viability and migration in the malignant progression of breast cancer.

Exploring new diagnostic biomarkers and molecular targets is of great importance in breast cancer treatment. The present study investigated the effects of acetyl-CoA carboxylase (ACC) expression interference on the malignant progression of breast cancer cells. ACC expression was knocked down using a lentiviral vector and this was verified by quantitative polymerase chain reaction and western blotting. MCF-7 and MDA-MB-231 breast cancer cells were randomly allocated into the following groups: Normal breast cancer cells (control), breast cancer cells transduced with a negative control lentiviral vector and breast cancer cells transduced with an ACC knockdown lentiviral vector. Screening for stable transgenic strains was successful. Cell viability, apoptosis and migration were determined using Cell Counting Kit-8, flow cytometry and scratch test, respectively. The protein expression levels of N-cadherin, Vimentin and Bax were detected by western blotting. In addition, a nude mouse model of subcutaneous metastatic tumor was established using MCF-7 breast cancer cells, and tumor volume was assessed. Furthermore, pathological condition and apoptosis were detected using hematoxylin and eosin, and TUNEL staining, respectively. The protein expression levels of N-cadherin, Vimentin and Bax were detected by western blotting. The in vitro experiments showed that knockdown of ACC expression significantly decreased the viability and migration, and increased the apoptosis of MCF-7 and MDA-MB-231 breast cancer cells. In vivo experiments revealed that ACC knockdown effectively reduced the tumor volume in nude mice, and promoted tumor cell apoptosis. Both in vitro and in vivo experiments showed that ACC knockdown can reduce the protein expression levels of N-cadherin and Vimentin, and increase Bax expression. These findings suggested that downregulation of ACC expression may significantly reduce the malignant progression of breast cancer, and could be considered a potential therapeutic target.

PARP inhibitor plus chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: a systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: Chemotherapy is the standard treatment for triple-negative breast cancer (TNBC). Whether the addition of PARP inhibitors improves treatment efficacy remains controversial clinically. Thus, we performed a meta-analysis to compare the efficacy and safety of combination treatment (PC) and chemotherapy alone (CA). METHODS: Relevant studies were identified through searches of 7 databases. The primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We screened 317 studies and included seven RCTs involving 2091 patients in the final analysis. PC tended to have better efficacy than CA according to PFS (HR [hazard ratio]: 0.83 [0.75, 0.93], p = 0.001), OS (HR: 0.89 [0.76,1.03], p = 0.11) and overall response rate (ORR) (RR [risk ratio]: 1.19 [0.97,1.46], p = 0.10). However, grade 3-5 AEs (RR: 1.50 [0.87,2.61], p = 0.15) were observed in the PC group. In the PC arm, the 10 most-reported grade 3-5 AEs were neutropenia (62.8%), anemia (28.5%), thrombocytopenia (26.4%), lymphopenia (19.05%), leukopenia (16.9%), fatigue (5%), heart failure (4.76%), lung infection (4.76%), thromboembolic events (4.76%) and ventricular tachycardia (4.76%). Similar results for pathological complete response (pCR), total AEs, rate of complete response (CR), stable disease (SD) and progressive disease (PD), breast conservation rate (BCR), and drug discontinuation (DD) rate were found between the two groups. CONCLUSIONS: For TNBC treatment, the combination of PARP inhibitors and chemotherapy appears to be superior to chemotherapy alone with better antitumor efficacy. However, its higher rate of AEs needs to be taken seriously. More high-quality RCTs are needed to confirm these results.

SNORA71B promotes breast cancer cells across blood-brain barrier by inducing epithelial-mesenchymal transition.

BACKGROUND: Brain metastasis (BM) is a dreadful complication that significantly impacts the quality of life in breast cancer patients. A key process during brain metastasis is the migration of cancer cells across blood-brain barrier (BBB). However, the role of snoRNAs regulating BBB in BM is still unknown. METHODS: Here SNORic and GEO databases were used to identify differentially expressed snoRNAs between brain metastatic and non-metastatic breast cancer (BC) tissues. The effects of SNORA71B on the capacities of proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and BBB invasion of BC cells were evaluated by CCK8, transwell, western blot, and BBB model, respectively. RESULTS: SNORA71B was highly expressed in high BM BC tissues and cells compared to low BM BC controls. Survival analysis revealed high expression of SNORA71B was significantly associated with poor PPS and OS in breast cancer patients. ROC curve showed that SNORA71B might act as biomarker for breast cancer. Moreover, SNORA71B significantly promoted proliferation, migration, and invasion of BC cells with different BM abilities. Importantly, SNORA71B promoted the EMT process of low BM BC cells. SNORA71B knockdown inhibited the high BM BC cells across BBB, while EMT activator dramatically abrogated this inhibited effect. CONCLUSIONS: In conclusion, SNORA71B promotes BC cells across the BBB partly via inducing EMT.

EMT related circular RNA expression profiles identify circSCYL2 as a novel molecule in breast tumor metastasis.

Substantial evidence indicates that circular RNAs (circRNAs) play vital roles in several diseases, especially in cancer development. However, the functions of circRNAs in breast cancer metastasis remain to be investigated. This study aimed to identify the key circRNAs involved in epithelial mesenchymal transition (EMT) of breast cancer and evaluated their molecular function and roles in pathways that may be associated with tumor metastasis. An EMT model was constructed by treating breast cancer cells MCF­7 and MDA­MB­231 with transforming growth factor­ß1. High­throughput RNA sequencing was used to identify the differentially expressed circRNAs in EMT and blank groups of two cells, and reverse transcription­quantitative PCR was used to validate the expression of circSCYL2 in human breast cancer tissues and cells. The effects of circSCYL2 on breast cancer cells were explored by transfecting with plasmids and the biological roles were assessed using transwell assays. EMT groups of breast cancer cells exhibited the characteristics of mesenchymal cells. Furthermore, the present study found that 7 circRNAs were significantly upregulated in both the MCF­7 EMT and MDA­MB­231 EMT groups, while 16 circRNAs were significantly downregulated. The current study identified that circSCYL2 was downregulated in breast cancer tissues and cell lines, and that circSCYL2 overexpression inhibited cell migration and invasion. This study provides expression profiles of circRNAs in EMT groups of breast cancer cells. circSCYL2, which is downregulated in breast cancer tissues and cells, may play an important role in breast cancer EMT progression.

Long noncoding RNA LINC00115 promotes breast cancer metastasis by inhibiting miR-7.

Breast cancer is the second leading cause of cancer-related deaths in women. The long noncoding RNA LINC00115 has been reported to be involved in the poor outcome of patients with breast cancer, but the biological function and underlying mechanism remain unclear. Here, we report that LINC00115 expression is increased in triple-negative breast cancer tissue compared with matched normal tissue, and LINC00115 knockdown suppresses breast cancer cell migration and invasion. Furthermore, we show that LINC00115 directly targets miR-7 and inhibits its expression. LINC00115 also reduces the expression of KLF4, which is a direct target of miR-7 and is involved in breast cancer metastasis. Together, our findings suggest that LINC00115 promotes breast cancer metastasis through modulating the expression of miR-7 and KLF4.

Anastrozole plus fulvestrant vs. anastrozole alone for hormone receptor-positive advanced breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: For patients with hormone receptor (HR)-positive advanced breast cancer, whether the combination of anastrozole and fulvestrant is more effective than anastrozole alone is controversial. Our meta-analysis aimed to compare the efficacy and safety of the two therapies. METHODS: We retrieved relevant studies in Embase, the Cochrane Library, Ovid MEDLINE, PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the disease control rate (DCR), the objective response rate (ORR), and adverse events (AEs). RESULTS: Five articles based on 4 randomized controlled trials containing 2146 patients were identified in our meta-analysis. The combination group had better efficacy in the endpoints of OS (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.74-0.99, p = 0.03) and PFS (HR 0.87; 95% CI 0.77-0.97, p = 0.02). Regarding the ORR, DCR, total AEs and grade 3-5 AEs, we found no difference between the two treatments. The combination group showed a clearly higher rate of treatment discontinuations (95% CI 1.05-3.60, p = 0.03) and AEs leading to death (95% CI 1.12-9.11, p = 0.03). The subgroup analysis of AEs showed an increased incidence of extremity or muscle pain, hematologic effects, gastrointestinal disorders, and hot flashes in the combination group. CONCLUSIONS: For HR-positive advanced breast cancer patients, the combination of anastrozole and fulvestrant appears to be superior to anastrozole alone in extending PFS and OS, despite relatively serious AEs.