Tilt Angle and Theoretical Target Strength of the Japanese Sandeel, Ammodytes personatus Captured on the Northern Coast of Hokkaido, Japan.

The tilt angle, i.e., the angle from horizontal made by the fish body as its head dives down or up, affects the readings on fish echo soundings. We measured the tilt angle of Japanese sandeels (Ammodytes personatus Girard) in a water tank, and calculated the acoustic target strength (TS) using a theoretical scattering model. This study examined the TS of sandeels from the northern coast of Hokkaido, which have a larger body size than those in other regions in Japan. TS values for sandeels, a swimbladderless fish, were estimated using a distorted-wave Born approximation (DWBA) model at two frequencies: 38 and 120 kHz. The mean tilt angle was 20.4?? (S.D. = 18.5??), which differed slightly from that of the lesser sandeel, Ammodytes marinus. The regression equations of the average TS values were TS38kHz = 8.2 log10SL ??? 74.2 and TS120kHz = 20.9 log10SL ??? 92.6, respectively. At 120 kHz, the slope was close to 20, suggesting that the acoustic backscattering strength was proportional to the square of the body length. This value was smaller at 38 kHz, suggesting that the acoustic backscattering strength was stable to differences in body length. We obtained a small discrepancy for both frequencies (??TS = TS120kHz???TS38kHz) were TS120kHz < TS38kHz. Discrepancies of ???1.3 dB for the maximum TS, and ???1.8 dB for averaged TS were found in 72 fish samples, which would be useful for identifying sandeel schools in practical analysis using TS differences

Chronic Hepatitis B Virus Infection and Rubella Susceptibility Among Obstetric Population in Metropolis Antenatal Centre Kano, Nigeria

It is well known that hepatitis B virus (HBV) infection is endemic in Nigeria. However, increased rubella susceptibility has been shown in patients from the Asian pacific region where chronic HBV infection is endemic. This study was carried out to assess the relationship between chronic HBV infection and rubella susceptibility in obstetric population aged 15–47 years attending Antenatal Clinic at Muhammad Abdullahi Wase Specialist Hospital Kano, Nigeria. From a total of 288 patients screened, 31 (10.76%) were reactive for HBsAg, meanwhile 50 (17.36%) were reactive to rubella IgM. Among the 31 infected patients 15 (48.39%) were from 20 – 24 years age bracket representing the most  susceptible age group while the infection rate was lowest (0.35%) in 45 – 49  age group (P = 0.00). The results of serological markers shows that HBsAg (+) was found in all 31 subjects (100%), anti HBs (+) 0 (0.00%), HBeAg (+) 3 (9.68%); anti HBe (+) and anti HBc (+) 24 (77.42%) respectively (P = 0.09). The study of liver enzymes activity among the HBV positive patients shows abnormal Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) among HBsAg (+) and HBeAg (+) group. However, abnormal Alkaline phospatase (ALP) was found to be non-significantly different between HBsAg (+) and HBeAg (+) vsHBsAg (+) and HBeAg (-) groups (P=0.00). Moreover, obstetric histories such as abortion still birth and neonatal deaths among various age groups with respect to rubella was also studied, it implies that  out of the 50 reactive patients, 35(12.15%) had a previous abnormal obstetric history (P=0.02). In a comparative study conducted, it was observed that HBV carriers were (25.81%) susceptible to rubella as against (12.91%) observed in HBV free subjects (positive correlation). The study demonstrates strong associations between chronic HBV infection and rubella susceptibility among the studied population

Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells.</p> <p>Methods</p> <p>HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed.</p> <p>Results</p> <p>5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21^Cip1and p27^Kip1and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU.</p> <p>Conclusion</p> <p>Our findings suggest that the combination therapy with CQ should be a novel therapeutic modality to improve efficacy of 5-FU-based chemotherapy, possibly by inhibiting autophagy-dependent resistance to chemotherapy.</p

Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Pregnane X receptor (PXR) is a key transcription factor that regulates drug metabolizing enzymes such as cytochrome P450 (CYP) 3A4, and plays important roles in intestinal first-pass metabolism. Although there is a large inter-individual heterogeneity with intestinal CYP3A4 expression and activity, the mechanism driving these differences is not sufficiently explained by genetic variability of PXR or CYP3A4. We examined whether epigenetic mechanisms are involved in the regulation of PXR/CYP3A4 pathways in colon cancer cells.</p> <p>Methods</p> <p>mRNA levels of PXR, CYP3A4 and vitamin D receptor (VDR) were evaluated by quantitative real-time PCR on 6 colon cancer cell lines (Caco-2, HT29, HCT116, SW48, LS180, and LoVo). DNA methylation status was also examined by bisulfite sequencing of the 6 cell lines and 18 colorectal cancer tissue samples. DNA methylation was reversed by the treatment of these cell lines with 5-aza-2'-deoxycytidine (5-aza-dC).</p> <p>Results</p> <p>The 6 colon cancer cell lines were classified into two groups (high or low expression cells) based on the basal level of PXR/CYP3A4 mRNA. DNA methylation of the CpG-rich sequence of the <it>PXR </it>promoter was more densely detected in the low expression cells (Caco-2, HT29, HCT116, and SW48) than in the high expression cells (LS180 and LoVo). This methylation was reversed by treatment with 5-aza-dC, in association with re-expression of PXR and CYP3A4 mRNA, but not VDR mRNA. Therefore, PXR transcription was silenced by promoter methylation in the low expression cells, which most likely led to downregulation of CYP3A4 transactivation. Moreover, a lower level of <it>PXR </it>promoter methylation was observed in colorectal cancer tissues compared with adjacent normal mucosa, suggesting upregulation of the PXR/CYP3A4 mRNAs during carcinogenesis.</p> <p>Conclusions</p> <p><it>PXR </it>promoter methylation is involved in the regulation of intestinal PXR and CYP3A4 mRNA expression and might be associated with the inter-individual variability of the drug responses of colon cancer cells.</p

Mieap, a p53-Inducible Protein, Controls Mitochondrial Quality by Repairing or Eliminating Unhealthy Mitochondria

Maintenance of healthy mitochondria prevents aging, cancer, and a variety of degenerative diseases that are due to the result of defective mitochondrial quality control (MQC). Recently, we discovered a novel mechanism for MQC, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins (designated MALM for Mieap-induced accumulation of lysosome-like organelles within mitochondria). However, a large part of the mechanisms for MQC remains unknown. Here, we report additional mechanisms for Mieap-regulated MQC. Reactive oxygen species (ROS) scavengers completely inhibited MALM. A mitochondrial outer membrane protein NIX interacted with Mieap in a ROS-dependent manner via the BH3 domain of NIX and the coiled-coil domain of Mieap. Deficiency of NIX also completely impaired MALM. When MALM was inhibited, Mieap induced vacuole-like structures (designated as MIV for Mieap-induced vacuole), which engulfed and degraded the unhealthy mitochondria by accumulating lysosomes. The inactivation of p53 severely impaired both MALM and MIV generation, leading to accumulation of unhealthy mitochondria. These results suggest that (1) mitochondrial ROS and NIX are essential factors for MALM, (2) MIV is a novel mechanism for lysosomal degradation of mitochondria, and (3) the p53-Mieap pathway plays a pivotal role in MQC by repairing or eliminating unhealthy mitochondria via MALM or MIV generation, respectively

Potential use of COX-2–aromatase inhibitor combinations in breast cancer

Cyclooxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Cyclooxygenase-2-positive tumours tend to be larger, higher grade, node-positive and HER-2/neu-positive. High COX-2 expression is associated with poor prognosis. Cyclooxygenase-2 inhibition reduces the incidence of tumours in animal models, inhibits the development of invasive cancer in colorectal cancer and reduces the frequency of polyps in familial adenomatous polyposis (FAP). These effects may be as a result of increased apoptosis, reduced angiogenesis and/or proliferation. Studies of COX-2 inhibitors in breast cancer are underway both alone and in combination with other agents. There is evidence to suggest that combining COX-2 inhibitors with aromatase inhibitors, growth factor receptor blockers, or chemo- or radiotherapy may be particularly effective. Preliminary results from combination therapy with celecoxib and exemestane in postmenopausal women with advanced breast cancer showed that the combination increased the time to recurrence. Up to 80% of ductal carcinomas in situ (DCISs) express COX-2, therefore COX-2 inhibition may be of particular use in this situation. Cyclooxygenase-2 expression correlates strongly with expression of HER-2/neu. As aromatase inhibitors appear particularly effective in patients with HER-2/neu-positive tumours, the combination of aromatase inhibitors and COX-2 inhibitors may be particularly useful in both DCIS and invasive cancer

Breast cancer chemoprevention: beyond tamoxifen

A large number of new potential chemoprevention agents are available that target molecular abnormalities found in estrogen receptor (ER)-negative and/or ER-positive precancerous breast tissue and have side effect profiles that differ from tamoxifen. Classes of agents currently undergoing evaluation in clinical prevention trials or those for which testing is planned in the near future include new selective ER modulators, aromatase inactivators/inhibitors, gonadotrophin-releasing hormone agonists, monoterpenes, isoflavones, retinoids, rexinoids, vitamin D derivatives, and inhibitors of tyrosine kinase, cyclooxygenase-2, and polyamine synthesis. New clinical testing models will use morphological and molecular biomarkers to select candidates at highest short-term risk, to predict the response to a particular class of agent, and to assess the response in phase II prevention trials. If validated, morphological and molecular markers could eventually replace cancer incidence as an indicator of efficacy in future phase III trials