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51.
Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL) cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated α-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia–retinoic acid receptor α (PML-RAR-α) stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-α activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-α does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation.  相似文献   
52.
Health risk for well drinking water is a worldwide problem. Our recent studies showed increased toxicity by exposure to barium alone (≤700 µg/L) and coexposure to barium (137 µg/L) and arsenic (225 µg/L). The present edition of WHO health-based guidelines for drinking water revised in 2011 has maintained the values of arsenic (10 µg/L) and barium (700 µg/L), but not elements such as manganese, iron and zinc. Nevertheless, there have been very few studies on barium in drinking water and human samples. This study showed significant correlations between levels of arsenic and barium, but not its homologous elements (magnesium, calcium and strontium), in urine, toenail and hair samples obtained from residents of Jessore, Bangladesh. Significant correlation between levels of arsenic and barium in well drinking water and levels in human urine, toenail and hair samples were also observed. Based on these results, a high-performance and low-cost adsorbent composed of a hydrotalcite-like compound for barium and arsenic was developed. The adsorbent reduced levels of barium and arsenic from well water in Bangladesh and Vietnam to <7 µg/L within 1 min. Thus, we have showed levels of arsenic and barium in humans and propose a novel remediation system.  相似文献   
53.
Biological Trace Element Research - The essential trace element zinc maintains liver functions. Liver diseases can alter overall zinc concentrations, and hypozincemia is associated with various...  相似文献   
54.
α-Amylase, which plays an essential role in starch degradation, is expressed mainly in the pancreas and salivary glands. Human α-amylase is also detected in other tissues, but it is unclear whether the α-amylase is endogenously expressed in each tissue or mixed exogenously with one expressed by the pancreas or salivary glands. Furthermore, the biological significance of these α-amylases detected in tissues other than the pancreas and salivary glands has not been elucidated. We discovered that human α-amylase is expressed in intestinal epithelial cells and analyzed the effects of suppressing α-amylase expression. α-Amylase was found to be expressed at the second-highest messenger RNA level in the duodenum in human normal tissues after the pancreas. α-Amylase was detected in the cell extract of Caco-2 intestinal epithelial cells but not secreted into the culture medium. The amount of α-amylase expressed increased depending on the length of the culture of Caco-2 cells, suggesting that α-amylase is expressed in small intestine epithelial cells rather than the colon because the cells differentiate spontaneously upon reaching confluence in culture to exhibit the characteristics of small intestinal epithelial cells rather than colon cells. The α-amylase expressed in Caco-2 cells had enzymatic activity and was identified as AMY2B, one of the two isoforms of pancreatic α-amylase. The suppression of α-amylase expression by small interfering RNA inhibited cell differentiation and proliferation. These results demonstrate for the first time that α-amylase is expressed in human intestinal epithelial cells and affects cell proliferation and differentiation. This α-amylase may induce the proliferation and differentiation of small intestine epithelial cells, supporting a rapid turnover of cells to maintain a healthy intestinal lumen.  相似文献   
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56.
11β-hydroxysteroid dehydrogenase (HSD11B) catalyzes the interconversion between active and inactive glucocorticoid, and is known to exist as two distinct isozymes: HSD11B1 and HSD11B2. A third HSD11B isozyme, HSD11B1L (SCDR10b), has recently been identified. Human HSD11B1L, which was characterized as a unidirectional NADP+-dependent cortisol dehydrogenase, appears to be specifically expressed in the brain. We previously reported that HSD11B1 and abundant HSD11B2 isozymes are expressed in neonatal pig testis and the Km for cortisol of NADP+-dependent dehydrogenase activity of testicular microsomes obviously differs from the same activity catalyzed by HSD11B1 from pig liver microsomes. Therefore, we hypothesized that the neonatal pig testis also expresses the third type of HSD11B isozyme, and we herein examined further evidence regarding the expression of HSD11B1L. (1) The inhibitory effects of gossypol and glycyrrhetinic acid on pig testicular microsomal NADP+-dependent cortisol dehydrogenase activity was clearly different from that of pig liver microsomes. (2) A highly conserved human HSD11B1L sequence was observed by RT-PCR in a pig testicular cDNA library. (3) mRNA, which contains the amplified sequence, was evaluated by real-time PCR and was most strongly expressed in pig brain, and at almost the same levels in the kidney as in the testis, but at lower levels in the liver. Based on these results, neonatal pig testis appears to express glycyrrhetinic acid-resistant HSD11B1L as a third HSD11B isozyme, and it may play a physiologically important role in cooperation with the abundantly expressed HSD11B2 isozyme in order to prevent Leydig cell apoptosis or GC-mediated suppression of testosterone production induced by high concentrations of activated GC in neonatal pig testis.  相似文献   
57.
To elucidate the specific interactions between the peroxisome proliferator-activated receptor (PPARα) and ligand GW409544 (GW), we obtained the solvated structures of the PPARα+GW complexes for human, mouse and rat by classical molecular mechanics calculations, and investigated their electronic properties by ab initio fragment molecular orbital calculations. The results indicate that the positively charged amino acids (Lys and Arg) of PPARα make a major contribution to the binding between PPARα and GW. In addition, it was clarified that Ser280 and Tyr314 of human and rat PPARα have a large attractive interaction with GW, while Ser280, Tyr314 and His440 of mouse PPARα have large interaction. These results on the difference in specific interactions between human and mouse/rat PPARα will be useful for predicting the effects of new chemicals on the human body based on the biomedical studies for the experimental animals such as mouse and rat.  相似文献   
58.
Gerodontology 2012; doi: 10.1111/j.1741‐2358.2012.00673.x Functional tooth units and nutritional status of older people in care homes in Indonesia Objectives: To investigate the relationship between functional tooth units (FTUs) and nutritional status. Methods: One hundred females (mean age: 72.4 ± 8.2 years) at four private care homes in Jakarta, Indonesia were interviewed and clinically examined. The oral examination included the assessment of teeth, prosthetic status, and number of FTUs. The total number of FTUs was further divided by tooth composition: natural tooth against natural tooth (NN‐FTUs), natural tooth against denture (ND‐FTUs), and denture against denture (DD‐FTUs). Nutritional status was evaluated using the body mass index (BMI) and the Mini Nutritional Assessment (MNA). Results: The mean numbers of teeth present, NN‐FTUs, ND‐FTUs, DD‐FTUs, and total FTUs were 13.1 ± 10.4, 1.7 ± 3.0, 1.2 ± 3.3, 0.4 ± 1.2 and 3.3 ± 4.4, respectively. The mean BMI and MNA scores were 24.8 ± 5.0 and 22.6 ± 2.8, respectively. Subjects with a normal BMI had a significantly higher total number of FTUs (3.6 ± 4.6) compared with underweight subjects (0.1 ± 0.3). Subjects with a normal MNA had a significantly higher number of NN‐FTU (2.6 ± 3.7) compared to those who were at risk or in a state of under‐nutrition (1.2 ± 2.4). Conclusion: This study revealed significant relationships between the number of FTUs and nutritional status. Keeping the posterior occlusion should be emphasized in order to maintain good nutritional status in older subjects.  相似文献   
59.
The present study was an attempt to identify the location of genioglossal respiratory and swallowing motoneuron cell bodies within the hypoglossal (XII) nucleus using both electrophysiological and morphological studies. The genioglossus muscle is innervated by the genioglossal branch of the medial XII nerve. At the entrance to the muscle, the genioglossal branch divides in the directions of the mandible and tongue. Five of five rats displayed both respiratory-related and swallowing-related bursts in the medial XII branch towards the mandible. All five rats also displayed swallowing-related bursts in the medial XII branch towards the tongue. In addition, horseradish peroxidase conjugated to wheatgerm agglutinin (HRP:WGA) was injected into the proximal cut ends of each branch. When HRP:WGA was injected into the branch in the direction of the mandible, HRP-labeled cells were detected in the lateral region of the ventromedial subnucleus in the XII nucleus, extending from 0.7 to 1.2 mm rostral to the obex. On the other hand, after injection into the branch in the direction of the mandible, HRP-labeled cells were detected in the ventromedial subnucleus of the XII nucleus, extending from 0.3 to 1.2 mm rostral to the obex. These results provide evidence that genioglossal respiration-related and swallowing-related motoneurons are located in different portions within the ventromedial subnucleus of the XII nucleus.  相似文献   
60.
Activation and inactivation of voltage-gated sodium channels (Navs) are well studied, yet the molecular mechanisms governing channel gating in the membrane remain unknown. We present two conformations of a Nav from Caldalkalibacillus thermarum reconstituted into lipid bilayers in one crystal at 9 Å resolution based on electron crystallography. Despite a voltage sensor arrangement identical with that in the activated form, we observed two distinct pore domain structures: a prominent form with a relatively open inner gate and a closed inner-gate conformation similar to the first prokaryotic Nav structure. Structural differences, together with mutational and electrophysiological analyses, indicated that widening of the inner gate was dependent on interactions among the S4–S5 linker, the N-terminal part of S5 and its adjoining part in S6, and on interhelical repulsion by a negatively charged C-terminal region subsequent to S6. Our findings suggest that these specific interactions result in two conformational structures.  相似文献   
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