Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise.

OBJECTIVES: Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. METHODS: We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. RESULTS: Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. CONCLUSION: These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts.Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601-608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2.

SV40 T/t-common polypeptide inhibits angiogenesis and growth of HER2-overexpressing human ovarian cancer.

Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in human ovarian cancers and its overexpression is associated with increased angiogenesis, increased metastasis and reduced survival. Inhibition of HER2 in HER2-overexpressing cancers can lead to reduced angiogenesis and improved survival. Previously, we reported that SV40 T/t-common polypeptide has transcriptional repression activity and can inhibit HER2 expression. In this study, we investigated the effect of T/t-common on the angiogenesis-inducing activity of HER2-overexpressing human SK-OV-3 ovarian cancer cells. We found that compared to conditioned medium from control SK-OV-3 cancer cells, conditioned medium from T/t-common-expressing SK-OV-3 cells had a reduced ability to induce endothelial cell migration and tube formation in vitro and microvessel formation in vivo. These data indicate that T/t-common can inhibit the ability of SK-OV-3 cancer cells to induce angiogenesis. T/t-common was found to be able to downregulate the expression of several proangiogenic factors, including vascular endothelial growth factor-A, interleukin-8, basic fibroblast growth factor, matrix metalloproteinase-2 and urokinase-type plasminogen activator, and upregulate antiangiogenic factors, including thrombospondin-1 and tissue inhibitor of metalloproteinases-1 in SK-OV-3 cancer cells. Finally, we demonstrated that T/t-common could inhibit the angiogenesis and growth of HER2-overexpressing human ovarian tumor in NOD/SCID mice. Taken together, the data suggest that T/t-common had the potential to be developed as a new antiangiogenic agent specific for treating HER2-overexpressing ovarian cancers.

Molecular epidemiology of a Shigella flexneri outbreak in a mountainous township in Taiwan, Republic of China.

An outbreak of shigellosis occurred in a township of Nantou Conuty in central Taiwan from August to October in 1996. The infections extended to two neighboring townships and continued to the end of 1996. Forty cases were confirmed during the period, in contrast to only one confirmed case in Nantou County in 1996 before the outbreak. All of these 41 cases in 1996 were identified as infections with Shigella flexneri serotype 2a. In order to trace the source of the infections, the 41 isolates recovered were analyzed by plasmid profile and pulsed-field gel electrophoresis (PFGE). There was no correlation between the plasmid profile results and the PFGE results, and the latter were used for subtyping of the 41 isolates. Twenty-two isolates (53%) had the same NotI and XbaI PFGE patterns, and 4 isolates (10%) had an additional unstable plasmid band in their NotI patterns but otherwise had the same NotI and XbaI patterns as the 22 isolates. These 26 isolates were designated the outbreak strain, and of these, 24 appeared in eight villages in one township and 2 appeared in a neighboring township. Fourteen of the remaining 15 isolates, including the isolate recovered 7 months before the outbreak, had both NotI and XbaI PFGE patterns closely related to those of the outbreak strain, indicating that Shigella infections were endemic in the area. By tracing the first isolation dates of the outbreak strain in individual villages and the neighboring township, it was found that the strain spread along the major arterial road and its branch road as time passed. Our molecular typing results and epidemiological data demonstrated the endemic nature of the outbreak strain as well as a person-to-person mode of transmission for the widespread infections the strain caused.

Two amino acid residues of transposase contributing to differential transposability of IS1 elements in Escherichia coli.

Escherichia coli W3110 contains four types of IS1 elements in the chromosome. Using an insertion element entrapping system, we collected 116 IS1 plasmid insertion mutants, which resulted from a minimum of 26 independent IS1 insertion events. All of them had insertions of IS1 of the IS1A (IS1E and IS1G) type. Inspection of the transposase sequences of the four IS1 types and the IS1 of the resistance plasmid R100 showed that two amino acid residues, His-193 and Leu-217 of transposase, might contribute to differential transposability of IS1 elements in W3110. The two amino acid residues of the transposase in IS1A (IS1E and IS1G) were altered separately by site-directed mutagenesis, and each mutant was found to mediate transposition at a frequency about 30-fold lower than that of IS1A (IS1E and IS1G). Thus, the assumption that His-193 and Leu-217 of transposase contribute to differential transposability of IS1 elements in W3110 was confirmed.