Pharmacological Effects of Asiatic acid in Glioblastoma Cells under Hypoxia

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2hrs of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma

Phylogeny of the Infraorder Pentatomomorpha Based on Fossil and Extant Morphology, with Description of a New Fossil Family from China

<div><h3>Background</h3><p>An extinct new family of Pentatomomorpha, Venicoridae Yao, Ren & Cai <b>fam. nov.</b>, with 2 new genera and 2 new species (<em>Venicoris solaris</em> Yao, Ren & Rider <b>gen. & sp. nov.</b> and <em>Clavaticoris zhengi</em> Yao, Ren & Cai <b>gen. & sp. nov.</b>) are described from the Early Cretaceous Yixian Formation in Northeast China.</p> <h3>Methodology/Principal Findings</h3><p>A cladistic analysis based on a combination of fossil and extant morphological characters clarified the phylogenetic status of the new family and has allowed the reconstruction of intersuperfamily and interfamily relationships within the Infraorder Pentatomomorpha. The fossil record and diversity of Pentatomomorpha during the Mesozoic is discussed.</p> <h3>Conclusions/Significance</h3><p>Pentatomomorpha is a monophyletic group; Aradoidea and the Trichophora are sister groups; these fossils belong to new family, treated as the sister group of remainder of Trichophora; Pentatomoidea is a monophyletic group; Piesmatidae should be separated as a superfamily, Piesmatoidea. Origin time of Pentatomomorpha should be tracked back to the Middle or Early Triassic.</p> </div

Is consuming yoghurt associated with weight management outcomes? Results from a systematic review.

BACKGROUND: Yoghurt is part of the diet of many people worldwide and is commonly recognised as a 'health food'. Epidemiological studies suggest that yoghurt may be useful as part of weight management programs. In the absence of comprehensive systematic reviews, this systematic review investigated the effect of yoghurt consumption by apparently healthy adults on weight-related outcomes. METHODS: An extensive literature search was undertaken, as part of a wider scoping review, to identify yoghurt studies. A total of 13 631 records were assessed for their relevance to weight-related outcomes. RESULTS: Twenty-two publications were eligible according to the review protocol. Cohort studies (n=6) and cross-sectional studies (n=7) all showed a correlation between yoghurt and lower or improved body weight/composition. Six randomised controlled trials (RCTs) and one controlled trial had various limitations, including small size and short duration. One RCT showed significant effects of yoghurt on weight loss, but was confounded by differences in calcium intake. One trial showed nonsignificant weight gain and the remaining five trials showed nonsignificant weight losses that were greater in yoghurt consumers. CONCLUSIONS: Yoghurt consumption is associated with lower body mass index, lower body weight/weight gain, smaller waist circumference and lower body fat in epidemiological studies. RCTs suggest weight reduction effects, but do not permit determination of a cause-effect relationship. Well-controlled, adequately powered trials in research and community settings appear likely to identify a modest but beneficial effect of yoghurt consumption for prevention of weight gain and management of obesity. The ready availability of yoghurt (a nutrient-dense food) and its ease of introduction to most diets suggests that educating the public to eat yoghurt as part of a balanced and healthy diet may potentially contribute to improved public health. Future carefully designed RCTs could provide proof of principle and large community-based studies could determine the practical impact of yoghurt on body weight/composition

Histopathological alterations in Senegal sole, Solea Senegalensis, from a polluted Huelva estuary (SW, Spain)

As a component of a large research project to evaluate the effects of contaminants on fish health in the field, histopathological studies have been conducted to help establish causal relationship between pollutants (heavy metals and aromatic polycyclic hydrocarbons—PAHs) and histopathological responses in Senegal sole, Solea senegalensis, from an estuary of SW Spain. Heavy metals (As, Zn, Cd, Pb, Cu and Fe) and 16 PAHs (proprietary USEPA) concentrations in water, sediment and tissues (liver and gills) and histopathological alterations in S. senegalensis from three sampling sites of Ria de Huelva estuary during 2004–2006 years have been analysed. The histopathological studies revealed seasonal and spatial differences in the lesion grade of alterations observing the highest lesion grades in fish from Odiel River and autumn season. No significant differences were observed in the alterations prevalence between sampling sites, but significant differences were observed between seasons observing the highest prevalence in autumn season. However, calculated IPAT demonstrated a low–moderate impact of pollutants on health fish. Correlations between histopathological alterations and pollutants analysed were observed being heavy metals the group that presented a major number of correlations with alterations in several organs of S. senegalensis. In evaluating the general health of fish, the use of histopathological studies in recommended for making more reliable assessment of biochemical responses in fish exposed to a variety of environmental stressors. Statistical analysis using semiquantitative data on pathological lesions can help to establish correlation between cause (stressor) and effect (biomarker)

Detection of Ki-ras mutations in tissue and plasma samples of patients with pancreatic cancer using PNA-mediated PCR clamping and hybridisation probes

In the present study, we combined the PCR-clamping approach with melting curve analysis using mutant specific hybridisation probes and wild-type specific peptide nucleic acids (PNAs) to determine the genotypes of the most frequent point mutation in codon 12 of the proto-oncogene Ki-ras in tissue and plasma samples of patients with pancreatic cancer. The sensitivity of our assay was 1–5 × 10−5. The melting curve analysis of tissue samples of four patients revealed two valine mutations, one none-valine mutation and one wild-type sequence. Ki-ras alterations were found in 28% of DNAs (18 out of 64) of nonrelated plasma samples of 10 patients with ductal adenocarcinoma of the pancreas. The valine mutation was the predominantly detected gene alteration (83%). Out of ten patients investigated, four patients (40%) became positive during clinical observation with respect to Ki-ras mutation. All four patients exhibited progressive disease and high levels of tumour marker CA 19-9. In conclusion, the one-step procedure discribed may be a useful clinical tool for analysing Ki-ras point mutations in tissue and plasmas samples. In addition, this method can be adapted for simultanous detection of multiple mutations and quantitation

An epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior

Developmental nicotine exposure causes persistent changes in cortical neuron morphology and in behavior. We used microarray screening to identify master transcriptional or epigenetic regulators mediating these effects of nicotine and discovered increases in Ash2lmRNA, encoding a component of a histone methyltransferase complex. We therefore examined genome-wide changes in trimethylation of histone H3 on Lys4 (H3K4me3), a mark induced by the Ash2l complex associated with increased gene transcription. A large proportion of regulated promoter sites were involved in synapse maintenance. We found that Mef2c interacts with Ash2l and mediates changes in H3K4me3. Knockdown of Ash2l or Mef2c abolished nicotine-mediated alterations of dendritic complexity in vitro and in vivo, and attenuated nicotine-dependent changes in passive avoidance behavior. In contrast, overexpression mimicked nicotine-mediated alterations of neuronal structure and passive avoidance behavior. These studies identify Ash2l as a target induced by nicotinic stimulation that couples developmental nicotine exposure to changes in brain epigenetic marks, neuronal structure and behavior

Macrophages in Breast Cancer: Do Involution Macrophages Account for the Poor Prognosis of Pregnancy-Associated Breast Cancer?

Macrophage influx is associated with negative outcomes for women with breast cancer and has been demonstrated to be required for metastasis of mammary tumors in mouse models. Pregnancy-associated breast cancer is characterized by particularly poor outcomes, however the reasons remain obscure. Recently, post-pregnancy mammary involution has been characterized as having a wound healing signature. We have proposed the involution-hypothesis, which states that the wound healing microenvironment of the involuting gland is tumor promotional. Macrophage influx is one of the prominent features of the involuting gland, identifying the macrophage a potential instigator of tumor progression and a novel target for breast cancer treatment and prevention

Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy

<p>Abstract</p> <p>Background</p> <p>Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment.</p> <p>Methods</p> <p>We established an <it>in vitro</it> approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed.</p> <p>Results</p> <p>Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel.</p> <p>Conclusions</p> <p>Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs.</p

It's not too Late for the Harpy Eagle (Harpia harpyja): High Levels Of Genetic Diversity and Differentiation Can Fuel Conservation Programs

Article on the harpy eagle (Harpia harpyja) and how high levels of genetic diversity and differentiation can fuel conservation programs