Resveratrol reverses tumor-promoter-induced inhibition of gap-junctional intercellular communication

The naturally occurring stilbene/alexin trans-resveratrol (trans-3,5, 4'-trihydroxystilbene) is a promising agent for the prevention of cancer. We investigated the effect of resveratrol on gap-junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells because inhibition of GJIC is an important mechanism of tumor promotion. Seventeen to 50 microM resveratrol increased GJIC significantly by a factor of 1.3 compared with solvent vehicle controls, when the WB-F344 cells were exposed to resveratrol for 6 h. Most tumor promoters, including the phorbol ester TPA and the insecticide DDT, block GJIC. Resveratrol at 17-50 microM also significantly prevented down-regulation of GJIC by TPA and DDT, by a factor of 2.7 and 1.8, respectively. This recovery of GJIC from TPA inhibition was partly correlated with hindered hyperphosphorylation of Cx43. In conclusion, resveratrol was found to enhance GJIC and counteract the effects of tumor promoters on GJIC, and this is likely a mechanism that contributes to the antipromotional and anticarcinogenic properties of resveratrol.     

Magnetite nanoparticles can be coupled to microbubbles to support multimodal imaging

Microbubbles (MBs) are commonly used as injectable ultrasound contrast agent (UCA) in modern ultrasonography. Polymer-shelled UCAs present additional potentialities with respect to marketed lipid-shelled UCAs. They are more robust; that is, they have longer shelf and circulation life, and surface modifications are quite easily accomplished to obtain enhanced targeting and local drug delivery. The next generation of UCAs will be required to support not only ultrasound-based imaging methods but also other complementary diagnostic approaches such as magnetic resonance imaging or computer tomography. This work addresses the features of MBs that could function as contrast agents for both ultrasound and magnetic resonance imaging. The results indicate that the introduction of iron oxide nanoparticles (SPIONs) in the poly(vinyl alcohol) shell or on the external surface of the MBs does not greatly decrease the echogenicity of the host MBs compared with the unmodified one. The presence of SPIONs provides enough magnetic susceptibility to the MBs to accomplish good detectability both in vitro and in vivo. The distribution of SPIONs on the shell and their aggregation state seem to be key factors for the optimization of the transverse relaxation rate.     

LYP inhibits T-cell activation when dissociated from CSK

Lymphoid tyrosine phosphatase (LYP) and C-terminal Src kinase (CSK) are negative regulators of signaling mediated through the T-cell antigen receptor (TCR) and are thought to act in a cooperative manner when forming a complex. Here we studied the spatiotemporal dynamics of the LYP-CSK complex in T cells. We demonstrate that dissociation of this complex is necessary for recruitment of LYP to the plasma membrane, where it downmodulates TCR signaling. Development of a potent and selective chemical probe of LYP confirmed that LYP inhibits T-cell activation when removed from CSK. Our findings may explain the reduced TCR-mediated signaling associated with a single-nucleotide polymorphism that confers increased risk for certain autoimmune diseases, including type 1 diabetes and rheumatoid arthritis, and results in expression of a mutant LYP that is unable to bind CSK. Our compound also represents a starting point for the development of a LYP-based treatment of autoimmunity.     

Simple ways to measure behavioral responses of Drosophila to stimuli and use of these methods to characterize a novel mutant

The behavioral responses of adult Drosophila fruit flies to a variety of sensory stimuli--light, volatile and non-volatile chemicals, temperature, humidity, gravity, and sound--have been measured by others previously. Some of those assays are rather complex; a review of them is presented in the Discussion. Our objective here has been to find out how to measure the behavior of adult Drosophila fruit flies by methods that are inexpensive and easy to carry out. These new assays have now been used here to characterize a novel mutant that fails to be attracted or repelled by a variety of sensory stimuli even though it is motile.     

Does Helicobacter pylori infection per se cause gastric cancer or duodenal ulcer? Inadequate evidence in Mongolian gerbils and inbred mice

A role for Helicobacter pylori infection in the development of gastric cancer in humans is well established; however, evidence for its carcinogenicity in animals remains inadequate. Mongolian gerbils and mice are commonly used to investigate the carcinogenicity of H. pylori, yet it is unclear whether H. pylori infection per se causes gastric cancer or duodenal ulcers in these animal models. Gastric adenocarcinoma in the gerbils was reported over 10 years ago, but this species has proved an unreliable model for studying H. pylori infection-associated gastric cancer. Helicobacter pylori infection alone appears insufficient to induce gastric cancer in these animals; additional carcinogenic insult is required. The development of invasive adenocarcinoma in inbred mice is rare regardless of the mouse or bacterial strain, and many long-term studies have failed to induce gastric cancer in these animals. Helicobacter pylori infection is also an established causative factor for duodenal ulcer in humans. However, few studies have attempted to develop animal models of H. pylori infection-induced duodenal ulcer. We therefore conclude that both Mongolian gerbils and inbred mice may be inadequate models for studying H. pylori infection-associated gastric cancer and that there is no animal model of H. pylori infection-induced duodenal ulcer.     

Population dynamics and production of the small copepod Oithona spp. in a subarctic fjord of West Greenland

The small cyclopoid copepod Oithona is widely occurring in polar areas; however, knowledge of its biology and ecology is very limited. Here, we investigate the population dynamics, vertical distribution, and reproductive characteristics of Oithona spp. from late winter to summer, in a subarctic fjord of West Greenland. During winter–early spring, the abundance of Oithona spp. was low (1.8 × 10³ ind. m^?2) and the population was mainly composed of late copepodites and adults, whereas in summer, abundance peaked and younger stages dominated (1.1 × 10⁶ ind. m^?2). In general, all stages of Oithona spp. remained in the upper 100 m, with nauplii exhibiting a shallower distribution. Although no general seasonal migration was found, a deeper distribution of the adult females in winter was observed. The mean clutch size of Oithona spp. varied from 16 to 30 eggs per female, peaking in summer. Egg production rates (EPR) were low in winter–early spring (0.13 ± 0.03 eggs female^?1 day^?1) and reached maximum values in summer (1.6 ± 0.45 eggs female^?1 day^?1). EPR of Oithona spp. showed a significantly positive relationship with both temperature and protozooplankton biomass, and the development of the population seemed to be appreciably affected by temperature. Oithona spp. remained active throughout the study, stressing the key importance of these small copepods in high-latitude ecosystems, especially in periods when larger copepods are not present in the surface layer.     

Bartonella henselae Endocarditis in Laos – ‘The Unsought Will Go Undetected’

Background

Both endocarditis and Bartonella infections are neglected public health problems, especially in rural Asia. Bartonella endocarditis has been described from wealthier countries in Asia, Japan, Korea, Thailand and India but there are no reports from poorer countries, such as the Lao PDR (Laos), probably because people have neglected to look.

Methodology/Principal Findings

We conducted a retrospective (2006–2012), and subsequent prospective study (2012–2013), at Mahosot Hospital, Vientiane, Laos, through liaison between the microbiology laboratory and the wards. Patients aged >1 year admitted with definite or possible endocarditis according to modified Duke criteria were included. In view of the strong suspicion of infective endocarditis, acute and convalescent sera from 30 patients with culture negative endocarditis were tested for antibodies to Brucella melitensis, Mycoplasma pneumoniae, Bartonella quintana, B. henselae, Coxiella burnetii and Legionella pneumophila. Western blot analysis using Bartonella species antigens enabled us to describe the first two Lao patients with known Bartonella henselae endocarditis.

Conclusions/Significance

We argue that it is likely that Bartonella endocarditis is neglected and more widespread than appreciated, as there are few laboratories in Asia able to make the diagnosis. Considering the high prevalence of rheumatic heart disease in Asia, there is remarkably little evidence on the bacterial etiology of endocarditis. Most evidence is derived from wealthy countries and investigation of the aetiology and optimal management of endocarditis in low income countries has been neglected. Interest in Bartonella as neglected pathogens is emerging, and improved methods for the rapid diagnosis of Bartonella endocarditis are needed, as it is likely that proven Bartonella endocarditis can be treated with simpler and less expensive regimens than “conventional” endocarditis and multicenter trials to optimize treatment are required. More understanding is needed on the risk factors for Bartonella endocarditis and the importance of vectors and vector control.     

High Reinfection Rate after Preventive Chemotherapy for Fishborne Zoonotic Trematodes in Vietnam

Background

The World Health Organization aims for complete morbidity control of fishborne zoonotic trematodes (FZT) in endemic areas by 2020. The main intervention tool for achieving this goal is regular use of preventive chemotherapy by offering praziquantel to those at risk in endemic areas. The purpose of this study was to investigate the effectiveness of preventive chemotherapy to control FZT in an endemic area in Northern Vietnam.

Methodology and principle findings

We followed a cohort of 396 people who fulfilled the criteria for receiving preventive chemotherapy. Stool samples were examined by Kato-Katz technique for the presence of trematode eggs before, and two, 16, 29 and 60 weeks after preventive chemotherapy. The prevalence of trematode eggs in stool was 40.2% before, 2.3% two weeks after and increased to a cumulative prevalence of 29.8% sixty weeks after preventive chemotherapy.

Conclusions

The effectiveness of preventive chemotherapy as a main component in control of FZT is not well documented in most endemic areas. We found a high reinfection rate within the first year after preventive chemotherapy. Since these trematodes are zoonoses, preventive chemotherapy may not have sufficient impact alone on the transmission to have a lasting effect on the prevalence. Animal reservoirs and farm management practices must be targeted to achieve sustainable control of fishborne zoonotic trematode infections, hence control programs should consider a One Health approach.     

Dietary gamma-linolenate attenuates tumor growth in a rodent model of prostatic adenocarcinoma via suppression of elevated generation of PGE(2) and 5S-HETE

Prostate cancer poses considerable threat to the aging male population as it has become a leading cause of cancer death to this group. Due to the complexity of this age-related disease, the mechanism(s) and factors resulting in prostate cancer remain unclear. Reports showing an increase risk in prostatic cancer with increasing dietary fat are contrasted by other studies suggesting the beneficial effects of certain polyunsaturated fatty acid (PUFA) in the modulation of tumor development. The n-6 PUFA, gamma-linolenic acid (GLA), has been shown to suppress tumor growth in vitro. Therefore, using the Lobund-Wistar (L-W) rat model of prostate cancer, we tested the hypothesis whether dietary supplementation of GLA could suppress tumor growth and development in vivo. Prostatic adenocarcinomas were induced in two groups of L-W rats, the experimental group (N-nitroso-N-methylurea, NMU/testosterone propionate, TP) and the GLA group (NMU/TP/GLA fed) undergoing similar treatment but fed a purified diet supplemented with GLA. Our findings revealed a decrease in prostate growth in the NMU/TP/GLA-fed group as determined by weight, tissue size, DNA content and prostate-specific antigen (tumor marker of prostate cancer). Comparison between the two groups showed a significant increase in 5S-hydroxyeicosatetraenoic acid and prostaglandin E(2) in the NMU/TP group. These increases paralleled the increased protein expression and activity of cyclooxygenase-2 as well as increased activity of 5-lipoxygenase. Taken together, the findings showed that intake of GLA-enriched diet does reduce prostatic cancer development in L-W rats and could serve as a non-toxic adjunct in management of human prostatic cancer.     

3T3-L1 adipocyte glucose transporter (HepG2 class): sequence and regulation of protein and mRNA expression by insulin, differentiation, and glucose starvation

A glucose transporter cDNA (GLUT) clone was isolated from mouse 3T3-L1 adipocytes and sequenced. The nucleotide and deduced amino acid sequences were, respectively, 95 and 99% homologous to those of the rat brain transporter. The mouse cDNA and a polyclonal antibody recognizing the corresponding in vitro translation product were used to compare changes in transporter mRNA and protein levels during differentiation, glucose starvation, and chronic insulin exposure of 3T3-L1 preadipocytes. The respective cellular content of transporter mRNA and protein were increased 6.6- and 7.8-fold during differentiation, and 3.8- and 2.5-fold from chronic insulin exposure of differentiated adipocytes. Glucose starvation increased transporter mRNA and protein levels 2.2- and 3.5-fold in undifferentiated preadipocytes and 1.8- and 3.1-fold in differentiated adipocytes. Starvation of undifferentiated cells completely converted the native transporter to an incompletely glycosylated form, while increasing basal transport rates 4.5-fold. Either full glycosylation is not required to produce a functionally active transporter, or starvation causes a unique predifferentiation induction of the normally absent "responsive" transporter. The changes in transporter protein expression elicited by differentiation were attributed primarily to increased rates of transporter synthesis, while the disproportionate changes in mRNA and protein expression from chronic insulin treatment and starvation suggested these conditions increase synthesis and decrease turnover rates in regulating transporter protein expression. Although chronic insulin exposure and glucose starvation each raised the expression of transporter protein greater than 3-fold and basal transport rates 2.5- to 4.5-fold, no significant increase in the insulin responsiveness of 3T3-L1 preadipocytes or differentiated adipocytes was observed. Thus, the changes in the transporter mRNA and protein expression observed in this study were most consistent with their being associated with the regulated expression of a basal or low level insulin-responsive transporter.