ZNF507 affects TGF-β signaling via TGFBR1 and MAP3K8 activation in the progression of prostate cancer to an aggressive state

Background: The progression of prostate cancer (PC) to the highly aggressive metastatic castration-resistant prostate cancer (mCRPC) or neuroendocrine prostate cancer (NEPC) is a fatal condition and the underlying molecular mechanisms are poorly understood. Here, we identified the novel transcriptional factor ZNF507 as a key mediator in the progression of PC to an aggressive state. Methods: We analyzed ZNF507 expression in the data from various human PC database and high-grade PC patient samples. By establishment of ZNF507 knockdown and overexpression human PC cell lines, we assessed in vitro PC phenotype changes including cell proliferation, survival, migration and invasion. By performing microarray with ZNF507 knockdown PC cells, we profiled the gene clusters affected by ZNF507 knockdown. Moreover, ZNF507 regulated key signal was evaluated by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Finally, we performed xenograft and in vivo metastasis assay to confirm the effect of ZNF507 knockdown in PC cells. Results: We found that ZNF507 expression was increased, particularly in the highly graded PC. ZNF507 was also found to be associated with metastatic PC of a high grade. Loss- or gain-of-function–based analysis revealed that ZNF507 promotes the growth, survival, proliferation, and metastatic properties of PC (e.g., epithelial-mesenchymal transition) by upregulating TGF-β signaling. Profiling of gene clusters affected by ZNF507 knockdown revealed that ZNF507 positively regulated the transcription of TGFBR1, MAP3K8, and FURIN, which in turn promoted the progression of PC to highly metastatic and aggressive state. Conclusions: Our findings suggest that ZNF507 is a novel key regulator of TGF-β signaling in the progression of malignant PC and could be a promising target for studying the development of advanced metastatic PCs. © 2021, The Author(s).1

Vertical Vibration of Mouse Osteoblasts Promotes Cellular Differentiation and Cell Cycle Progression and Induces Aging In Vitro

Background: This study aimed to investigate the effect of the vibration of osteoblasts on the cell cycle, cell differentiation, and aging. Materials and Methods: Primary maxilla osteoblasts harvested from eight-week-old mice were subjected to vibration at 3, 30, and 300 Hz once daily for 30 min; control group, 0 Hz. A cell proliferation assay and Cell-Clock Cell Cycle Assay were performed 24 h after vibration. Osteoblast differentiation assay, aging marker genes, SA-β-Gal activity, and telomere length (qPCR) were assayed two weeks post- vibration once every two days. Results: Cell proliferation increased significantly at 30 and 300 Hz rather than 0 Hz. Several cells were in the late G2/M stage of the cell cycle at 30 Hz. The osteoblast differentiation assay was significantly higher at 30 Hz than at 0 Hz. Runx2 mRNA was downregulated at 30 Hz compared to that at 0 Hz, while osteopontin, osteocalcin, and sclerostin mRNA were upregulated. p53/p21, p16, and c-fos were activated at 30 Hz. SA-β-Gal activity increased significantly at 30 or 300 Hz. Telomere length was significantly lower at 30 or 300 Hz. Conclusions: The results suggest that providing optimal vibration to osteoblasts promotes cell cycle progression and differentiation and induces cell aging

Postoperative white blood cell counts change after pancreatoduodenectomy: Early sign for pancreatic fistula

Purpose: Pancreatic surgery is challenging and associated with high morbidity. Therefore, it is important to detect it early before it becomes clinically apparent. The white blood cell (WBC) count useful as a predictive marker of postoperative pancreatic fistula. The aim of this study was to evaluate the diagnostic accuracy of WBC in predicting pancreatic fistula. Methods: Between September 2003 and December 2013, 405 patients underwent elective pancreaticoduodenectomy or pylorus preserving pancreaticoduodenectomy for periampullary malignancy. Among them, 372 patients with no preoperative leukocytosis were enrolled in this study. The serum WBC count was monitored daily until postoperative day 8. The clinic and pathological data of these patients were analyzed by reviewing medical records retrospectively. Results: Thirty patients (8%) developed pancreatic fistula grade B and C. The WBC count, measured every other day, was significantly higher every other day during the first 7 postoperative days in patients who developed pancreatic fistula grade B and C, compared with those patients who did not develop pancreatic fistula. The WBC count cutoff value of 13.07×109/L, 10.37×109/L on postoperative day 1,7 yielded a sensitivity of 57%, 70%, specificity of 53%, 67% for the detection of pancreatic fistula. Conclusion: Patients with postoperative fistula grades B and C showed WBC counts that did not decrease on subsequent measurements during the early postoperative period. The measurement of WBC counts after pancreaticoduodenectomy can play a clinically important role in the early detection of pancreatic fistula development even from postoperative one day

Vertical Vibration of Mouse Osteoblasts Promotes Cellular Differentiation and Cell Cycle Progression and Induces Aging In Vitro

Background: This study aimed to investigate the effect of the vibration of osteoblasts on the cell cycle, cell differentiation, and aging. Materials and Methods: Primary maxilla osteoblasts harvested from eight-week-old mice were subjected to vibration at 3, 30, and 300 Hz once daily for 30 min; control group, 0 Hz. A cell proliferation assay and Cell-Clock Cell Cycle Assay were performed 24 h after vibration. Osteoblast differentiation assay, aging marker genes, SA-β-Gal activity, and telomere length (qPCR) were assayed two weeks post- vibration once every two days. Results: Cell proliferation increased significantly at 30 and 300 Hz rather than 0 Hz. Several cells were in the late G2/M stage of the cell cycle at 30 Hz. The osteoblast differentiation assay was significantly higher at 30 Hz than at 0 Hz. Runx2 mRNA was downregulated at 30 Hz compared to that at 0 Hz, while osteopontin, osteocalcin, and sclerostin mRNA were upregulated. p53/p21, p16, and c-fos were activated at 30 Hz. SA-β-Gal activity increased significantly at 30 or 300 Hz. Telomere length was significantly lower at 30 or 300 Hz. Conclusions: The results suggest that providing optimal vibration to osteoblasts promotes cell cycle progression and differentiation and induces cell aging

β-aminoisobutyric acid attenuates LPS-induced inflammation and insulin resistance in adipocytes through AMPK-mediated pathway

Abstract Background β-aminoisobutyric acid (BAIBA) is produced in skeletal muscle during exercise and has beneficial effects on obesity-related metabolic disorders such as diabetes and non-alcoholic fatty liver disease. Thus, it is supposed to prevent high fat diet (HFD)-induced inflammation and insulin resistance in adipose tissue though anti-inflammatory effects in obesity. Previous reports have also demonstrated strong anti-inflammatory effects of BAIBA. Methods We used BAIBA treated fully differentiated 3T3T-L1 mouse adipocytes to investigate the effects of exogenous BAIBA on inflammation and insulin signaling in adipocytes. Insulin signaling-mediated proteins and inflammation markers were measured by Western blot analysis. Secretion of pro-inflammatory cytokines were measured by ELISA. Lipid accumulation in differentiated 3 T3-L1 cells was stained by Oil red-O. Statistical analysis was performed by ANOVA and student’s t test. Results BAIBA treatment suppressed adipogenesis assessed by adipogenic markers as well as lipid accumulation after full differentiation. We showed that BAIBA treatment stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner and lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as TNFα and MCP-1 was abrogated in BAIBA-treated 3 T3-L1 cells. Treatment of 3 T3-L1 cells with BAIBA reduced LPS-induced NFκB and IκB phosphorylation. Furthermore, BAIBA treatment ameliorated LPS-induced impairment of insulin signaling measured by IRS-1 and Akt phosphorylation and fatty acid oxidation. Suppression of AMPK by small interfering (si) RNA significantly restored these changes. Conclusions We demonstrated anti-inflammatory and anti-insulin resistance effects of BAIBA in differentiated 3 T3-L1 cells treated with LPS through AMPK-dependent signaling. These results provide evidence for the beneficial effects of BAIBA not only in liver and skeletal muscle cells but also in adipose tissue

Real-time in vivo two-photon imaging study reveals decreased cerebro-vascular volume and increased blood-brain barrier permeability in chronically stressed mice

Chronic stress disrupts brain homeostasis and adversely affects the cerebro-vascular system. Even though the effects of chronic stress on brain system have been extensively studied, there are few in vivo dynamic studies on the effects of chronic stress on the cerebro-vascular system. In this study, the effects of chronic stress on cerebral vasculature and BBB permeability were studied using in vivo two-photon (2p) microscopic imaging with an injection of fluorescence-conjugated dextran. Our realtime 2p imaging results showed that chronic stress reduced the vessel diameter and reconstructed vascular volume, regardless of vessel type and branching order. BBB permeability was investigated with two different size of tracers. Stressed animals exhibited a greater BBB permeability to 40-kDa dextran, but not to 70-kDa dextran, which is suggestive of weakened vascular integrity following stress. Molecular analysis revealed significantly higher VEGFa mRNA expression and a reduction in claudin-5. In summary, chronic stress decreases the size of cerebral vessels and increases BBB permeability. These results may suggest that the sustained decrease in cerebro-vascular volume due to chronic stress leads to a hypoxic condition that causes molecular changes such as VEGF and claudin-5, which eventually impairs the function of BBB © The Author(s) 201

A Study on the Transition of Copper Oxide by the Incorporation of Nitrogen

In the present study, the effects of nitrogen incorporation on the transition of a p-type copper oxide semiconductor are investigated. The properties of sputtered copper oxide and nitrogen-incorporated copper oxide are evaluated and compared at various nitrogen gas flow rates. The results indicate that the addition of nitrogen results in an increased optical bandgap, accompanied by significantly reduced tail states compared to pristine copper oxide. In addition, X-ray diffraction and X-ray photoelectron spectroscopy reveal that the incorporation of nitrogen stimulates the transition from copper (II) oxide to copper (I) oxide