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Objective: Breast cancer is one of the most common malignancies and a leading cause of cancer-related death in women worldwide. Both hormone-related factors and genetic aberrations could cause breast cancer. We investigated copy number alternations (CNAs) on four breast cancer-susceptible loci, namely 2q35-rs13387042, 3p24-rs4973768, 17q23-rs6504950, and fibroblast growth factor receptor 2 (FGFR2)-rs2981578, in Taiwanese women. Patients and Methods: Breast cancer tissues and blood samples from 66 patients and their clinical data were collected from a human biobank. The copy numbers of the germline samples (from blood) and cancer tissues from each patient on the susceptible loci – 2q35, 3p24, 17q23, and FGFR2 – were obtained using TaqMan probes in the Applied Biosystems Inc., (ABI) StepOnePlus Real-Time Polymerase Chain Reaction instrument and CopyCaller® Software v1.0 (ABI, CA, USA). Results: The mean copy numbers output by CopyCaller® Software v1.0 of the cancer tissues on these susceptible loci (2q35, 3p24, 17q23, and FGFR2) from the 66 patients were higher than those of the blood samples (2.0 vs. 1.9); however, significantly higher copy numbers for cancer tissues compared with germline samples were discovered only on 2q35-rs13387042 (P = 0.035). In addition, patients with advanced breast cancers had relatively many CNAs between their cancer tissues and germline samples on 17q23-rs6504950 (P = 0.008). Multivariate analysis revealed that the risk factor for patients with advanced breast cancers was CNAs between cancer tissues and germline samples on 17q23-rs6504950 (odds ratio = 13.337, 95% confidence interval: 1.525–122.468). Conclusions: CNAs on 17q23-rs6504950 between cancer tissues and germline samples could affect cancer progression in Taiwanese women with breast cancer. Further investigations regarding the role of CNAs on 17q23-rs6504950 in cancer progression are necessary to elucidate the pathogenesis of breast cancer. [ABSTRACT FROM AUTHOR]

Summary: Objective: Type 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%‐95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA‐219 (miR‐219) on inhibition of long‐term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DM mice through the N‐methyl‐d‐aspartate receptor (NMDAR) signaling pathway regulation. Methods: The T2DM mouse models were established, after which LTP in vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured. Next, the density of pyramidal neurons in each group was calculated. Additionally, the expression levels of miR‐219, the NMDAR signaling pathway [NMDAR1 (NR) 1, NR2A, and NR2B), downstream target proteins [calmodulin‐dependent protein kinase‐II (CaMK‐II) and cAMP response element binding protein (CREB)], and apoptosis‐related factors [Bcl2‐associated X protein (Bax), c‐caspase‐9 and c‐caspase‐3] in the hippocampal tissues were determined. Finally, immunohistochemistry was applied to detect and measure the positive expression of Bax, caspase‐9, and caspase‐3 proteins. Results: The results showed that upregulation of miR‐219 increases LTP and density of pyramidal neurons in the hippocampal tissues of mice, while it decreases blood glucose of db/db mice. In addition, miR‐219 upregulation also leads to decreased mRNA levels of NR1, NR2A, NR2B, CaMK‐II, and CREB and protein levels of NR1, NR2A, NR2B, CaMK‐II, CREB, p‐CREB, Bax, c‐caspase‐9, and c‐caspase‐3. Furthermore, upregulation of miR‐219 inhibits positive expression of Bax, caspase‐9, and caspase‐3 proteins, leading to the suppression of hippocampal neuronal cell apoptosis. Conclusion: The findings from this study indicated that the upregulation of miR‐219 decreases LTP inhibition and hippocampal neuronal cell apoptosis in T2DM mice by downregulating the NMDAR signaling pathway, therefore suggesting that MiR‐219 might be a future therapeutic strategy for T2DM. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is one of the most common malignancies and a leading cause of cancer-related death in women worldwide. Both hormone-related factors and genetic aberrations could cause breast cancer. We investigated copy number alternations (CNAs) on four breast cancer-susceptible loci, namely 2q35-rs13387042 , 3p24-rs4973768 , 17q23-rs6504950 , and fibroblast growth factor receptor 2 ( FGFR2 )-rs2981578, in Taiwanese women., Patients and Methods: Breast cancer tissues and blood samples from 66 patients and their clinical data were collected from a human biobank. The copy numbers of the germline samples (from blood) and cancer tissues from each patient on the susceptible loci - 2q35 , 3p24 , 17q23 , and FGFR2 - were obtained using TaqMan probes in the Applied Biosystems Inc., (ABI) StepOnePlus Real-Time Polymerase Chain Reaction instrument and CopyCaller ® Software v1.0 (ABI, CA, USA)., Results: The mean copy numbers output by CopyCaller ® Software v1.0 of the cancer tissues on these susceptible loci ( 2q35, 3p24, 17q23 , and FGFR2 ) from the 66 patients were higher than those of the blood samples (2.0 vs. 1.9); however, significantly higher copy numbers for cancer tissues compared with germline samples were discovered only on 2q35-rs13387042 ( P = 0.035). In addition, patients with advanced breast cancers had relatively many CNAs between their cancer tissues and germline samples on 17q23-rs6504950 ( P = 0.008). Multivariate analysis revealed that the risk factor for patients with advanced breast cancers was CNAs between cancer tissues and germline samples on 17q23-rs6504950 (odds ratio = 13.337, 95% confidence interval: 1.525-122.468)., Conclusions: CNAs on 17q23-rs6504950 between cancer tissues and germline samples could affect cancer progression in Taiwanese women with breast cancer. Further investigations regarding the role of CNAs on 17q23-rs6504950 in cancer progression are necessary to elucidate the pathogenesis of breast cancer., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Tzu Chi Medical Journal.)

Aim: To investigate the protective effect of bifidobacterium in endotoxin-induced intestinal injury in preweaning rats., Methods: Preweaning rats were randomly divided into three groups (n = 40 for each): a control group (group C), a model group (group E) and a treatment group (group T). Both groups E and T were intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 5 mg/kg (5 mg/L in normal saline), and group T was intragastrically administrated with bifidobacterium suspension (2.0 × 10(9) CFU/mL, 0.5 mL each time, twice a day, until the end of the experiment) 7 d before LPS administration. Group C was intraperitoneally injected with normal saline. After intraperitoneal injection and intragastric administration, the rats were placed back to the initial cage to receive breast feeding. The rats were killed at 2, 6, 12, 24 or 72 h, respectively, after endotoxin or physiological saline injection to collect serum and ileal tissue samples. Myeloperoxidase (MPO) contents in serum and ileum were detected at different times, and expression of ileal defensin-5 mRNA was evaluated by reverse transcription-polymerase chain reaction., Results: Serum and ileal MPO contents in group E were significantly higher than those in group C (serum contents: 107.50 ± 17.70 vs 157.14 ± 24.67, P < 0.05; ileal contents: 1.03 ± 0.21 vs 1.57 ± 0.33, P < 0.05), which peaked at 12 h and 6 h, respectively. MPO contents in group T were significantly lower than those in group E (serum contents: 114.38 ± 24.56 vs 145.25 ± 23.62, P < 0.05; ileal contents: 1.25 ± 0.24 vs 1.57 ± 0.33, P < 0.05). The expression of defensin-5 mRNA in group E was significantly higher than that in group C (0.953 ± 0.238 vs 0.631 ± 0.146, P < 0.05), which peaked at 2 h, and then decreased gradually. The expression of defensin-5 mRNA in group T was significantly lower than that in group E (0.487 ± 0.149 vs 0.758 ± 0.160, P < 0.05) apparently in 24 h. The expression of defensin-5 mRNA at 2 h in group T was significantly higher than that in group C (0.824 ± 0.158 vs 0.631 ± 0.146, P < 0.05)., Conclusion: MPO and defensin-5 mRNA increase in preweaning rats with LPS-induced intestinal injury. Bifidobacterium protects the gut by inhibiting MPO activity, not by increasing defensin-5 secretion.