Carvacrol Alleviates Prostate Cancer Cell Proliferation, Migration, and Invasion through Regulation of PI3K/Akt and MAPK Signaling Pathways

TRPM7 is a potential therapeutic target for treatment of prostate cancer. In this study, we investigated the effects of nonselective TRPM7 inhibitor carvacrol on cell proliferation, migration, and invasion of prostate cancer PC-3 and DU145 cells. Our results showed that carvacrol blocked TRPM7-like currents in PC-3 and DU145 cells and reduced their proliferation, migration, and invasion. Moreover, carvacrol treatment significantly decreased MMP-2, p-Akt, and p-ERK1/2 protein expression and inhibited F-actin reorganization. Furthermore, consistently, TRPM7 knockdown reduced prostate cancer cell proliferation, migration, and invasion as well. Our study suggests that carvacrol may have therapeutic potential for the treatment of prostate cancer through its inhibition of TRPM7 channels and suppression of PI3K/Akt and MAPK signaling pathways

Comprehensive Analysis of Human Cytomegalovirus MicroRNA Expression during Lytic and Quiescent Infection

Background Human cytomegalovirus (HCMV) encodes microRNAs (miRNAs) that function as post-transcriptional regulators of gene expression during lytic infection in permissive cells. Some miRNAs have been shown to suppress virus replication, which could help HCMV to establish or maintain latent infection. However, HCMV miRNA expression has not been comprehensively examined and compared using cell culture systems representing permissive (lytic) and semi-permissive vs. non-permissive (latent-like) infection. Methods Viral miRNAs levels and expression kinetics during HCMV infection were determined by miRNA-specific stem-loop RT-PCR. HCMV infected THP-1 (non-permissive), differentiated THP-1 (d-THP-1, semi-permissive) and human embryo lung fibroblasts (HELs, fully-permissive) were examined. The impact of selected miRNAs on HCMV infection (gene expression, genome replication and virus release) was determined by Western blotting, RT-PCR, qPCR, and plaque assay. Results Abundant expression of 15 HCMV miRNAs was observed during lytic infection in HELs; highest peak inductions (11- to 1502-fold) occurred at 48 hpi. In d-THP-1s, fourteen mRNAs were detected with moderate induction (3- to 288-fold), but kinetics of expression was generally delayed for 24 h relative to HELs. In contrast, only three miRNAs were induced to low levels (3- to 4-fold) during quiescent infection in THP-1s. Interestingly, miR-UL70-3p was poorly induced in HEL (1.5-fold), moderately in THP-1s (4-fold), and strongly (58-fold) in d-THP-1s, suggesting a potentially specific role for miR-UL70-3p in THP-1s and d-THP-1s. MiR-US33, -UL22A and -UL70 were further evaluated for their impact on HCMV replication in HELs. Ectopic expression of miR-UL22A and miR-UL70 did not affect HCMV replication in HELs, whereas miR-US33 inhibited HCMV replication and reduced levels of HCMV US29 mRNA, confirming that US29 is a target of miR-US33. Conclusions Viral miRNA expression kinetics differs between permissive, semi-permissive and quiescent infections, and miR-US33 down-regulates HCMV replication. These results suggest that miR-US33 may function to impair entry into lytic replication and hence promote establishment of latency

Genetic effects of polymorphisms in candidate genes and the QTL region on chicken age at first egg

<p>Abstract</p> <p>Background</p> <p>The age at first egg (AFE), an important indicator for sexual maturation in female chickens, is controlled by polygenes. Based on our knowledge of reproductive physiology, 6 genes including gonadotrophin releasing hormone-I (<it>GnRH-I</it>), neuropeptide Y (<it>NPY</it>), dopamine D2 receptor (<it>DRD2</it>), vasoactive intestinal polypeptide (<it>VIP</it>), VIP receptor-1 (<it>VIPR-1</it>), and prolactin (<it>PRL</it>), were selected as candidates for influencing AFE. Additionally, the region between <it>ADL0201 </it>and <it>MCW0241 </it>of chromosome Z was chosen as the candidate QTL region according to some QTL databases. The objective of the present study was to investigate the effects of mutations in candidate genes and the QTL region on chicken AFE.</p> <p>Results</p> <p>Marker-trait association analysis of 8 mutations in those 6 genes in a Chinese native population found a highly significant association (P < 0.01) between <it>G840327C </it>of the <it>GnRH-I </it>gene with AFE, and it remained significant even with Bonferroni correction. Based on the results of the 2-tailed χ²test, mutations <it>T32742394C, T32742468C, G32742603A</it>, and <it>C33379782T </it>in the candidate QTL region of chromosome Z were selected for marker-trait association analysis. The haplotypes of <it>T32742394C </it>and <it>T32742468C </it>were significantly associated (P < 0.05) with AFE. Bioinformatics analysis indicated that <it>T32742394C </it>and <it>T32742468C </it>were located in the intron region of the SH3-domain GRB2-like 2 (<it>SH3GL2</it>) gene, which appeared to be associated in the endocytosis and development of the oocyte.</p> <p>Conclusion</p> <p>This study found that <it>G840327C </it>of the <it>GnRH-I </it>gene and the haplotypes of <it>T32742394C-T32742468C </it>of the <it>SH3GL2 </it>gene were associated with the chicken AFE.</p

Cardiac resynchronization therapy (CRT) with right ventricular sense triggered left ventricular pacing benefits for the hemodynamics compared with standard CRT for chronic congestive heart failure: A cross-over study

Background: The aim of this study was to investigate the effect of cardiac resynchronization therapy (CRT) with right ventricular (RV) sense triggered left ventricular (LV) pacing for chronic heart failure (CHF). Methods: Thirty patients who were eligible for the Class I indication of CRT were enrolled and the informed consents were signed. Left ventricular ejection fraction (LVEF), diastolic mitral flow velocity time integral (VTI), mitral regurgitation flow VTI, and aortic valve flow VTI were measured with GE Vivid 7 (GE Medical, Milwaukee, WI, USA) before and after CRT. The echocardiographic measurements and the average annual costs of the device use were compared. Results: The duration of QRS complex, the length of time used for optimization, and the average annual cost of the device use under RV sense triggered LV pacing were significantly less than that under standard biventricular (BiV) pacing (p &lt; 0.01), while the average battery lifetime was longer. Subgroup analysis showed that LVEF, diastolic mitral flow VTI, and aortic valve flow VTI under RV sense triggered LV pacing were greater than that under standard BiV pacing with right or LV pre-activation. The average battery lifetime was significantly longer and the average annual cost of the device use was less. The mitral regurgitation flow VTI under RV sense triggered LV pacing was less than that under standard BiV pacing with RV pre-activation. Conclusions: RV sense triggered LV provides benefits for CHF patients over standard CRT in terms of maintaining the physiological atrio-ventricular delay of atrio-ventricular node and improving the acute hemodynamic effects

Relationship between Obesity-related Hormone Peptides and Quality of Life in Obese Women among Different Traditional Chinese Medicine Syndrome Groups

AbstractThe aim of this study was to explore the relationship between obesity-related hormone peptides and quality of life in obese women among different traditional Chinese medicine (TCM) syndrome groups (證型 zhèng xíng). 260 obese women met with age between 20 and 65years old and body mass index (BMI) ≧ 27kg/m2, were recruited. The participants filled out a questionnaire on obese TCM syndrome groups, which was designed by professional TCM doctors, and two questionnaires on quality of life (QOL), WHOQOL-BREF Taiwan version and MOS Short Form-12 (SF-12). Data of biochemical characteristics and obesity-related hormone peptides were collected at the same time. According to the responses provided, the obese subjects were classified into spleen deficiency with dampness encumbrance syndrome (脾虛濕阻證 pí xū shī zǔ zhèng; SDD), stomach heat with dampness encumbrance syndrome (胃熱濕阻證 wèi rè shī zǔ zhèng; SHD), liver depression and qi stagnation syndrome (肝鬱氣滯證 gān yù qì zhì zhèng; LDQ), dual spleen-kidney deficiency syndrome (脾腎兩虛證 pí shèn liǎng xū zhèng; SKD), yin deficiency with internal heat syndrome (陰虛內熱證 yīn xū nèi rè zhèng; YDI) and a control group. For physical conditions, SDD group had significantly higher means in weight and BMI compared with the control group. The insulin and leptin levels in SHD group were significantly higher than those in the control group. The LDQ group showed marked decrease in mental condition scores compared with the control group. This study found that obese women in the SDD group were fatter than those in the control group. SHD group might have greater influence on the regulation of obesity-related hormone peptides. The LDQ group had poor QOL than the control group. Analysis of TCM syndrome groups among obese women merits further investigation

Model Tests on the Retaining Walls Constructed from Geobags Filled with Construction Waste

Geobag retaining wall using construction waste is a new flexible supporting structure, and the usage of construction waste to fill geobags can facilitate the construction recycling. In this paper, model tests were performed on geobag retaining wall using construction waste. The investigation was concentrated on the slope top settlement, the distribution characteristics of the earth pressures on retaining walls and horizontal wall displacements, and slope failure modes. The results indicated that the ultimate loads that the slope tops with retaining walls could bear were 87.5%~125% higher than that of the slope top without retaining walls. The ultimate loading of strengthened slopes with different slope ratios from 1 : 0.75 to 1 : 0.25 could be reduced by 11.8% to 29.4%. The horizontal displacements of the retaining walls constructed from geobags were distributed in a drum shape, with the greatest horizontal displacements occurring about 1/3~1/2 of the wall height away from the bottom of the wall. As the slope ratio increased, the failure of the slope soil supported by geobag retaining wall using construction waste changed from sliding to sliding-toppling (dominated by sliding) and then to toppling-sliding (dominated by toppling). The range of 1/3~1/2 of wall height is the weak part of the retaining walls, which should be strengthened with certain measures during the process of design and construction

Construction and expression of two-copy engineered yeast of feruloyl esterase

Background: Aspergillus niger has the ability to secrete feruloyl esterase. However, for economically viable industrial applications, it is necessary to increase their catalytic activities and/or protein yields to satisfy the increasing needs for feruloyl esterases. Results: The gene AnFaeA that encodes a type A feruloyl esterase was successfully expressed in Pichia pastoris by a two-copy engineered yeast. After a screen in shaker flask, a one-copy strain GSKFA3 having the highest feruloyl esterase activity of 2.4 U/mL was obtained. Then, the pPICZ\u3b1A-AnFaeA plasmid was transformed into GSKFA3 and the transformants were grown on YPDS plates with antibiotic Zeocin. After cultivation, a two-copy strain GSKZ\u3b1FA20 with the highest feruloyl esterase activity of 15.49 U/mL was obtained. The expressed protein (recombinant AnFaeA) may be a glycoprotein with an apparent molecular weight of 40 kDa. It displayed the maximum activity at pH 6.0 and 50\ub0C, and was stable at a pH range of 4.0\u20136.5 and at below 45\ub0C. Its activity was not significantly affected by K+, Ca2+, Mg2+, Cu2+, Zn2+, Mn2+, Na+ and EDTA, but activated by Fe2+. The Km and Vmax toward 4-nitrophenyl ferulate were 5.5 mM and 69.0 U/mg, respectively. Conclusions: The two-copy strain GSKZ\u3b1FA20 showed a 4.4-fold increase in extracellular enzyme activity compared with the one-copy strain GSKFA3. Construction of two-copy strain improved secretion of recombinant AnFaeA in P. pastoris