Violacein negatively modulates the colorectal cancer survival and epithelial-mesenchymal transition.

Violacein is a secondary metabolite produced by several microorganisms including Chromobacterium violaceum, and it is already used in food and cosmetics. However, due to its potent anticancer and low side effects, its molecular action needs to be deeply scrutinized. Therefore, the main objective of this study was to evaluate the violacein's ability to interfere with three cancer hallmarks: growth factors receptor-dependent signaling, proliferation, and epithelial-mesenchymal transition (EMT). Violacein has been associated with the induction of apoptosis in colorectal cancer (CRC) cells. Here, we demonstrate that this molecule is also active in CRC spheroids and inhibits cell migration. Violacein treatment reduced the amount of EGFR and AXL receptors in the HT29 cell line. Accordingly, the inhibition of the AKT, ERK, and PKCδ kinases, which are downstream mediators of the signaling pathways triggered by EGFR and AXL, is detected. Another interesting finding was that even when the cells were stimulated with transforming growth factor-ß, the EMT marker (N-cadherin) decreased. Therefore, this study provides further evidence that reinforces the potential of violacein as an antitumor agent, once this biomolecule can "switch off" properties associated with cancer plasticity.

Platelet-dependent signaling and Low Molecular Weight Protein Tyrosine Phosphatase expression promote aggressive phenotypic changes in gastrointestinal cancer cells.

Over the last decades, some members of the protein tyrosine phosphatase family have emerged as cancer promoters. Among them, the Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) has been described to be associated with colorectal cancer liver metastasis and poor prostate cancer prognosis. Of importance in the process of cancer progression and metastasis is the interaction between tumor cells and platelets, as the latter are thought to promote several tumor hallmarks. Here, we examine to what extent LMWPTP expression in tumor cells affects their interaction with platelets. We demonstrate that the gene encoding LMWPTP is overexpressed in upper gastrointestinal (GI) cancer cell as well as colorectal cancer, and subsequently employ cell line models to show that the level of this phosphatase may be further augmented in the presence of platelets. We demonstrate that tumor-platelet interaction promotes GI tumor cell proliferation. Additionally, using know-down/-out models we show that LMWPTP expression in cancer cells contributes to a more efficient interaction with platelets and drives platelet-induced proliferation. These data are the first to demonstrate that phosphatases play a positive role in the tumor-promoting activities of platelets, with LMWPTP emerging as a key player promoting oncogenic phenotypic changes in tumor cells.

LMWPTP modulates the antioxidant response and autophagy process in human chronic myeloid leukemia cells.

In the last decade, several reports highlight the importance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in cancer aggressiveness and resistance. Specifically, in chronic myeloid leukemia, we have reported that high expression of the LMWPTP maintains Src and Bcr-Abl kinases in an activated status and the glucose metabolism is directed to lactate production and, in turn, favor the pentoses pathway (one of the key process for antioxidant and protective responses). In this present study, we investigated the possible correlation between the LMWPTP and autophagy. In resistant chronic myeloid leukemia cells, the antioxidant response is supported by the glycolytic metabolism and antioxidant enzymes such as SOD and catalase, both favored by the LMWPTP. Therefore, when the cells were challenged by hydrogen peroxide treatment, the LMWPTP level goes down as well as SOD, and in turn, autophagy process was stimulated. The findings presented here reveal a novel aspect by which LMWPTP cooperates for the resistance of CML towards stressor stimuli.

Identification of oxidoreductases from the petroleum Bacillus safensis strain.

A gram-positive bacterium, denominated CFA-06, was isolated from Brazilian petroleum in the Campos Basin and is responsible for the degradation of aromatic compounds and petroleum aromatic fractions. The CFA-06 strain was identified as Bacillus safensis using the 16S rRNA and gyrase B sequence. Enzymatic assays revealed the presence of two oxidoreductases: a catalase and a new oxidoreductase. The oxidoreductases were enzymatically digested and analyzed via ESI-LTQ-Orbitrap mass spectrometry. The mass data revealed a novel oxidoreductase (named BsPMO) containing 224 amino acids and 89% homology with a hypothetic protein from B. safensis (CFA-06) and a catalase (named BsCat) with 491 amino acids and 60% similarity with the catalase from Bacillus pumilus (SAFR-032). The new protein BsPMO contains iron atom(s) and shows catalytic activity toward a monooxygenase fluorogenic probe in the presence of cofactors (NADH, NADPH and NAD). This study enhances our knowledge of the biodegradation process of petroleum by B. safensis.

Adipose-derived stromal cell therapy improves cardiac function after coronary occlusion in rats.

Recent studies have identified adipose tissue as a new source of mesenchymal stem cells for therapy. The purpose of this study was to investigate the therapy with adipose-derived stromal cells (ASCs) in a rat model of healed myocardial infarction (MI). ASCs from inguinal subcutaneous adipose tissue of male Wistar rats were isolated by enzymatic digestion and filtration. Cells were then cultured until passage 3. Four weeks after ligation of the left coronary artery of female rats, a suspension of either 100 µl with phosphate-buffered saline (PBS) + Matrigel + 2 × 10(6) ASCs labeled with Hoechst (n = 11) or 100 µl of PBS + Matrigel (n = 10) was injected along the borders of the ventricular wall scar tissue. A sham-operated group (n = 5) was submitted to the same surgical procedure except permanent ligation of left coronary artery. Cardiac performance was assessed by electro- and echocardiogram. Echo was performed prior to injections (baseline, BL) and 6 weeks after injections (follow-up, FU), and values after treatment were normalized by values obtained before treatment. Hemodynamic measurements were performed 6 weeks after injections. All infarcted animals exhibited cardiac function impairment. Ejection fraction (EF), shortening fractional area (SFA), and left ventricular akinesia (LVA) were similar between infarcted groups before treatment. Six weeks after therapy, ASC group showed significant improvement in all three ECHO indices in comparison to vehicle group. In anesthetized animals dp/dt(+) was also significantly higher in ASCs when compared to vehicle. In agreement with functional improvement, scar area was diminished in the ASC group. We conclude that ASCs improve cardiac function in infarcted rats when administered directly to the myocardium.

Molecular analysis of microbial diversity in corrosion samples from energy transmission towers.

Microbial diversity in corrosion samples from energy transmission towers was investigated using molecular methods. Ribosomal DNA fragments were used to assemble gene libraries. Sequence analysis indicated 10 bacterial genera within the phyla Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. In the two libraries generated from corroded screw-derived samples, the genus Acinetobacter was the most abundant. Acinetobacter and Clostridium spp. dominated, with similar percentages, in the libraries derived from corrosion scrapings. Fungal clones were affiliated with 14 genera belonging to the phyla Ascomycota and Basidiomycota; of these, Capnobotryella and Fellomyces were the most abundant fungi observed. Several of the microorganisms had not previously been associated with biofilms and corrosion, reinforcing the need to use molecular techniques to achieve a more comprehensive assessment of microbial diversity in environmental samples.

Granulocyte-colony stimulating factor treatment of chronic myocardial infarction.

PURPOSE: The aim of this study was to investigate the impact of granulocyte-colony stimulating factor (G-CSF) administration on cardiac function of rats with chronic myocardial infarction through two different protocols: high dose short term and low dose long term protocols. METHODS: Wistar rats were submitted to MI surgery and after 4 weeks they received recombinant human G-CSF (Filgrastim) or vehicle subcutaneously. We tested the classical protocol (50 microg/kg/day during 7 days) and the long term low dose treatment (four cycles of 5 days of 10 microg/kg/day). Cardiac performance was evaluated before, 4 and 6 weeks after G-CSF injections by electro- and echocardiography, hemodynamic and treadmill exercise test. RESULTS: All infarcted groups exhibited impaired function compared to sham operated animals. Moreover, all cardiac functional parameter were not different between G-CSF and Vehicle group at resting conditions as well as after treadmill exercise stress test, despite intense white blood cell mobilization in both protocols at all time points. Hypertrophy was not different and infarct size was similar in histological analysis CONCLUSIONS: These data clearly show that G-CSF treatment was unable to restore cardiac function impaired by myocardial infarction either with classical approach or long term low dose administration.

Birth prevalence and natural history of congenital cytomegalovirus infection in a highly seroimmune population.

BACKGROUND: The natural history of congenital cytomegalovirus (CMV) infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated the birth prevalence, clinical findings at birth, and hearing outcome in CMV-infected children from such a population. METHODS: Consecutively born infants were screened for the presence of CMV in urine and/or saliva specimens during the first 2 weeks after birth. Neonatal clinical findings were recorded, and CMV-infected children were tested to document hearing function during follow-up. A subset of mothers of CMV-infected infants were prenatally tested for the presence of anti-CMV immunoglobulin G antibodies. RESULTS: Congenital CMV infection was confirmed in 87 (1.08%; 95% confidence interval [CI], 0.86%-1.33%) of 8047 infants. Seven infants (8.1%; 95% CI, 3.3%-15.9%) had at least 1 clinical finding suggestive of CMV infection, and 4 (4.6%; 95% CI, 1.3%-11.3%) had >3 findings of systemic disease. Sensorineural hearing loss was found in 5 (8.6%; 95% CI, 2.9%-19.0%) of 58 children tested at a median age of 21 months. Bilateral profound hearing loss was observed in 2 children, and the hearing threshold was >60 decibels in all 5 children with hearing loss, including 2 children born to mothers with probable nonprimary CMV infection. CONCLUSIONS: The results of this large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates, with a similar incidence of CMV-related hearing loss to that reported in the offspring of women from populations in developed countries with lower rates of seroimmunity to CMV.