Investigation of TF-binding lectins from dietary sources and SRL on proliferation and cell cycle progression in human colon HT29 and SW620 cells

TF antigen binding lectins from dietary sources PNA, ACA, ABL, JAC, and SRL from Sclerotium rolfsii have been reported to induce diverse effects on cancer cell proliferation by different mechanisms. This study aimed to compare effects of these lectins on growth and cell cycle progression in colon cancer HT29 and SW620 cells. As reported SRL, ABL, and JAC inhibited while PNA and ACA increased cell proliferation. ABL and JAC treated HT29 cells showed increased cell population in G0/G1 phase. PNA, ACA, ABL, and JAC increased SW620 cell population in S and decreased in G2/M phase. In contrast, SRL and JAC increased hypodiploid population in both the cells. PNA and ACA reduced whereas SRL and ABL diminished cell cyclin D1 expression. SRL, PNA, and ACA also reduced cellular cyclin D3 level while SRL, ABL, and JAC reduced cyclin E levels. ABL decreased CDK5 levels while SRL and ACA completely abolished CDK5 expression. All the lectins completely abolished cyclin D2 expression. These results not only confirms growth regulatory effects of TF-binding lectins but also indicates different effects of these lectins on cell growth is associated with regulation on expression of cell cycle associated proteins in G1-S phase and on cell cycle progression.     

Short duration exercise increases breath hydrogen excretion after lactulose ingestion: description of a new phenomenon

OBJECTIVE: There is limited information on the effect of exercise on colonic function. Beneficial effects have been described, including prevention of colon cancer. In the present study, we demonstrate that short duration exercise results in enhancement of breath hydrogen excretion after consumption of lactulose. METHODS: Twelve normal volunteers who performed regular exercise were recruited. Each study subject underwent four study sessions (two resting and two exercise) after consumption of 10 g of crystalline lactulose. Colonic hydrogen production was measured in mid-expiratory breath samples obtained at baseline and frequent intervals to 420 min. Exercise sessions consisted of 5 min on a treadmill at a 20% incline at 10 km/h. This was performed 180 min after lactulose ingestion in the two exercise sessions. RESULTS: A characteristic pattern in the hydrogen concentration versus time curves was seen after exercises, consisting of an initial decrease then an increase in concentration above baseline for up to 3 h. Mean area under the curve from 0 to 420 min for resting studies was 5,156 +/- 2,621 ppm/min and was 7,051 +/- 2,447 ppm/min for exercise studies, p < 0.05 (37% increase). Mean area under the curve from 180 to 420 min was 2,808 +/- 1,592 ppm/min for resting studies and 4,543 +/- 1,729 for exercise studies, p < 0.005 (62% increase). CONCLUSION: This study demonstrates that exercise potentially enhances the metabolism of lactulose by colonic bacteria. The authors postulate that this effect is due to stirring of the colonic contents. The described phenomenon may explain, in part, the beneficial effects of exercise on colonic mucosa.     

Maternal Effects of Respiratory Syncytial Virus Infection during Pregnancy

Given the illness and deaths caused by respiratory syncytial virus (RSV) infection during the first year of life, preventing infant RSV infections through maternal vaccination is intriguing. However, little is known about the extent and maternal effects of RSV infection during pregnancy. We describe 3 cases of maternal RSV infection diagnosed at a US center during winter 2014. Case-patient 1 (26 years old, week 33 of gestation) received a diagnosis of RSV infection and required mechanical ventilation. Case-patient 2 (27 years old, week 34 of gestation) received a diagnosis of infection with influenza A(H1N1) virus and RSV and required mechanical ventilation. Case-patient 3 (21 years old, week 32 of gestation) received a diagnosis of group A streptococcus pharyngitis and RSV infection and was monitored as an outpatient. Clarifying the effects of maternal RSV infection could yield valuable insights into potential maternal and fetal benefits of an effective RSV vaccination program.     

The selection of L5 versus S1 in long fusions for adult idiopathic scoliosis

The treatment of adult spinal deformities often involves long thoracolumbar fusions into the lower lumbar spine, raising the debate of selecting L5 or S1 as the caudal extent of the fusion. The presence of significant deformity or degenerative pathologic findings at L5-S1 mandates fusion to the sacrum. Fusion to the sacrum is of larger magnitude than fusion to L5 and introduces a higher surgical complication rate. Advantages of ending the fusion at L5 include preservation of motion, avoiding the high complication rate associated with fusion to the sacrum, and possibly avoiding a second operation. Complications with fusion to L5 include possible loss of fixation and subsequent disc degeneration at L5-S1, however, leading to possible pain and loss of sagittal balance and the need for revision surgery. To date, the functional consequences of an open disc space beneath long constructs remain poorly defined, and there is no firm evidence in the literature guiding the surgeon's choice. The issues and evidence guiding the decision to fuse to L5 or S1 are examined in this article.     

Sodium/calcium exchanger expression in the mouse and rat olfactory systems

Sodium/calcium (Na(+)/Ca(2+)) exchangers are membrane transport systems that regulate Ca(2+)-homeostasis in many eukaryotic cells. In olfactory and vomeronasal sensory neurons ligand-induced olfactory signal transduction is associated with influx and elevation of intracellular Ca(2+), [Ca(2+)](i). While much effort has been devoted to the characterization of Ca(2+)-related excitation and adaptation events of olfactory chemosensory neurons (OSNs), much less is known about mechanisms that return [Ca(2+)](i) to the resting state. To identify proteins participating in the poststimulus Ca(2+)-clearance of mouse OSNs, we analyzed the expression of three potassium (K(+))-independent (NCX1, 2, 3) and three K(+)-dependent (NCKX1, 2, 3) Na(+)/Ca(2+) exchangers. In situ hybridization showed that mRNAs of all six Na(+)/Ca(2+) exchangers coexist in neurons of the olfactory and vomeronasal systems, and that some are already detectable in the embryo. Of these, NCX1 and NCKX1 represent the most and least abundant mRNAs, respectively. Moreover, immunohistochemistry revealed that the NCX1, 2, and 3 proteins are expressed in nearly all neurons of the olfactory epithelium, the vomeronasal organ, the septal organ of Masera, and the Grueneberg ganglion. These three exchanger proteins display different expression profiles in dendrites, knobs, and plasma membranes of OSNs and in sustentacular cells. Furthermore, we show that NCX1 mRNA in rat olfactory mucosa is expressed as 8 alternative splice variants. This is the first comprehensive analysis of Na(+)/Ca(2+) exchanger expression in the mammalian olfactory system. Our results suggest that Ca(2+)-extrusion by OSNs utilizes multiple different Na(+)/Ca(2+) exchangers and that different subtypes are targeted to different subcellular compartments.     

3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011: opener of large-conductance Ca(2+)-activated potassium (maxi-K) channels, identification, solubility, and SAR

Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.     

Occurrence and Correlates of Postpartum Depression in Overweight and Obese Women: Results from the Active Mothers Postpartum (AMP) Study

Objective Postpartum depression (PPD) is a significant concern for new mothers and their infants, as well as the health professionals who care for them. Obesity may be a risk factor for depression, and therefore, for PPD specifically. We examined the occurrence and risk factors for PPD in a sample of overweight and obese new mothers. Methods In this cross-sectional study, 491 women who were overweight or obese prior to pregnancy completed the Edinburgh Postnatal Depression Scale (EPDS) 6 weeks postpartum, along with a number of other health- and pregnancy-related measures. Occurrence of depression was investigated, as well as bivariate and multivariate relationships between depression and demographic and health-related characteristics. Results As determined by an EPDS score of 13 or higher, the prevalence of PPD was 9.2%. Three items on the scale stood out as drivers of the total score (“blame myself unnecessarily”, “anxious or worried,” “feel overwhelmed”). Bivariate correlates of depression included education, income, marital status, and self-reported chronic illness; income remained significant in the multivariate logistic regression model. BMI was not related to postpartum depression. Discussion In this group of overweight and obese women, there was no association between BMI group and postpartum depression.     

Uranium induces apoptosis in lung epithelial cells

Uranium is a naturally occurring radioactive material present everywhere in the environment. It is toxic because of its chemical or radioactive properties. Uranium enters environment mainly from mines and industry and cause threat to human health by accumulating in lungs as a result of inhalation. In our previous study, we have shown the effectiveness of antioxidant system response to the oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE) cells. As part of our continuing studies; here, we investigated the mechanism underlying when LE cells are exposed to different concentration of UA. Oxidative stress may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5 and 1 mM of UA results in dose and time-dependent increase in activity of both caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in cytosol was seen in LE cells treated with 1 mM UA as a result of mitochondria membrane permeability. The cytochrome-c leakage may trigger the apoptotic pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed significant incorporation of dNTPs in the nucleus after 24 h. In the presence of the caspase inhibitors, we observed the significant decrease in the activity of caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells.     

Secretome mediated interactions between sensory neurons and breast cancer cells

The role of the nervous system in aiding cancer progression and metastasis is an important aspect of cancer pathogenesis. Interaction between cancer cells and neurons in an in vitro platform is a simple and robust method to further understand this phenomenon. In our study, we aimed to examine in vitro reciprocal effect between breast cancer cells and cancer-sensitized peripheral primary sensory neurons. Secretome obtained from either cultured DRG neurons from tumor-burdened rats, or MRMT1 breast cancer cells were used to study neuronal and cancer cell reciprocity. We utilized neurite analysis, modified cell migration assay and cell signaling pathway inhibitors to determine neurite growth patterns and cell migration in PC12/DRG neurons and MRMT1 cells, respectively. MRMT1 secretome was found to induce significant neurite outgrowth in PC12 and primary sensory neurons. Secretome-induced neurite growth in PC12 cells was partly mediated by PI3K and ERK pathways, but not by adenylyl cyclase. Conversely, secretome from tumor-sensitized sensory neuron cultures induced increased rate of migration in cultured MRMT1 cells. Results from our study provide additional support to the hypothesis that both breast cancer cells and nerve terminals secrete signaling messengers that have a reciprocal effect on each other.