Chronic kidney disease (CKD) is a long-term condition in which the kidneys do not work correctly. It has a high prevalence and represents a serious hazard to human health and estimated to affects ...hundreds of millions of people. Diabetes and hypertension are the two principal causes of CKD. The progression of CKD is characterized by the loss of renal cells and their replacement by extracellular matrix (ECM), independently of the associated disease. Thus, one of the consequences of CKD is glomerulosclerosis and tubulointerstitial fibrosis caused by an imbalance between excessive synthesis and reduced breakdown of the ECM. There are many molecules and cells that are associated with progression of renal fibrosis e.g. angiotensin II (Ang II). Therefore, in order to understand the biopathology of renal fibrosis and for the evaluation of new treatments, the use of animal models is crucial such as: surgical, chemical and physical models, spontaneous models, genetic models and in vitro models. However, there are currently no effective treatments for preventing the progression of renal fibrosis. Therefore it is essential to improve our knowledge of the cellular and molecular mechanisms of the progress of renal fibrosis in order to achieve a reversion/elimination of renal fibrosis.
Cancer is the first cause of death in developed countries and the second in developing countries. Concerning the most frequent worldwide-diagnosed cancer, primary liver cancer represents ...approximately 4% of all new cancer cases diagnosed globally. However, among primary liver cancer, hepatocellular carcinoma is by far the most common histological subtype. Notwithstanding the health promotion and disease prevention campaigns, more than half a million new hepatocellular carcinoma cases are reported yearly, being estimated to growth continuously until 2020. Taking this scenario under consideration and the fact that some aspects concerning hepatocellular carcinoma evolution and metastasize process are still unknown, animal models assume a crucial role to understand this disease. The animal models have also provided the opportunity to screen new therapeutic strategies. The present review was supported on research and review papers aiming the complexity and often neglected chemically induced animal models in hepatocarcinogenesis research. Despite the ongoing debate, chemically induced animal models, namely, mice and rat, can provide unique valuable information on the biotransformation mechanisms against xenobiotics and apprehend the deleterious effects on DNA and cell proteins leading to carcinogenic development. In addition, taking under consideration that no model achieves all hepatocellular carcinoma research purposes, criteria to define the “ideal” animal model, depending on the researchers’ approach, are also discussed in this review.
The Aptian-Albian sedimentary record of the Parnaíba Basin (NE Brazil), represented by the Codó and Itapecuru formations, is characterized by near-shore, shallow marine, and fluvio-lacustrine clastic ...sediments deposited in a large shallow sag basin that developed during the breakup of northwestern Gondwana associated with the early opening stages of the South Atlantic. This study aims to precisely characterize the nature, variability, paleoenvironmental significance and preservation conditions of the organic matter of the Aptian-Albian succession of the 2-TV-1-MA borehole (270 m). With these premises, organic petrographic and geochemical techniques were applied for the definition of the organic facies, allowing a better understanding of the Parnaíba Basin evolution during the Aptian-Albian interval. The 2-TV-1-MA borehole presents, at the base, a lacustrine system, with a high contribution of continental components deposited in a high energy, oxic environment, with incipient marine influence. This is intercalated by periods of restriction, with deposition occurring in a dysoxic-anoxic, low energy environment, with high contribution of higher plants. To the top, a relative decrease in the water-column leads to an increase in restriction, the emplacement of a stratified water-column, and the development of microbial mats. This is topped by a return to a high energy, oxic environment, with marine influence, and dominance of higher plants organic components.
•Four depositional systems have been proposed for the 2-TV-1-MA well core.•A first marine influence in the initial stages of deposition of the Codó Fm.•Organic-rich levels with terrestrially-derived AOM coeval with OAE 1b.
Animal models, namely mice, have been used to study chemically induced carcinogenesis due to their similarity to the histological and genetic features of human patients. Hepatocellular carcinoma ...(HCC) is a common malignancy with poor clinical outcome. The high incidence of HCC might be related to exposure to known risk factors, including carcinogenic compounds, such as N-nitrosamines, which cause DNA damage. N-nitrosamines affect cell mitochondrial metabolism, disturbing the balance between reactive oxygen species (ROS) and antioxidants, causing oxidative stress and DNA damage, potentially leading to carcinogenesis. This work addresses the progressive histological changes in the liver of N-diethylnitrosamine (DEN)-exposed mice and its correlation with oxidative stress.
Male ICR mice were randomly divided into five DEN-exposed and five matched control groups. DEN was IP administered, once a week, for eight consecutive weeks. Samples were taken 18h after the last DEN injection (8 weeks post-exposure). The following sampling occurred at weeks 15th, 22nd, 29th and 36th after the first DEN injection.
DEN resulted in early toxic lesions and, from week 29 onwards, in progressive proliferative lesions. Between 15 and 29 weeks, DEN-exposed animals showed significant changes in hepatic antioxidant (glutathione, glutathione reductase, and catalase) status (p<0.05) compared with controls. These results point to an association between increased DEN-induced oxidative stress and the early histopathological alterations, suggesting that DEN disrupted the antioxidant defense mechanism, thereby triggering liver carcinogenesis.
Gaiteiros-1 borehole, located in the central Lusitanian Basin (Portugal), drilled a continuous Jurassic (Hettangian to Kimmeridgian) sedimentary sequence. Forty-one samples were selected for this ...study to characterize the dispersed organic matter and its vertical variation along Gaiteiros-1 borehole and to evaluate the environmental changes based on palynofacies and bulk geochemistry analyses.
Gaiteiros-1 borehole lithological sequence is characterized by a low organic carbon content, which varies between 0.10 wt% and 0.83 wt%, in Candeeiros carbonates and Lower Jurassic Coimbra Formation, respectively. The insoluble residue content indicate a carbonated character in almost the entire sequence, except for Kimmeridgian samples. The palynofacies analysis evidences the presence of the main groups of kerogen (Phytoclats, Amorphous and Palynomorphs) with a dominance of the amorphous group in the carbonated samples and phytoclasts in Kimmeridgian detritic samples. Different types of amorphous particles were identified, suggesting periods of reworking by bacterial activity and primary bioproductivity in depleted oxygen environments. Despite the dominance of amorphous particles, the kerogen groups vertical variation provides information that reveals changes in the depositional environment. The kerogen assemblage of the Candeeiros facies suggests a stratified water column, with well-oxygenated layers, responsible for high primary productivity periods, which allowed for the development of zooplankton, preserved in the form of zooclasts fragments and foraminiferal test-linings. The contribution of the Palynomorph group is scarce during the Lower-Middle Jurassic but increases in the Upper Jurassic. This modification in the kerogen assemblage reflects changes in the sea level, oxygenation conditions, climate and proximity to the terrestrial source area. The presence of Coleochaete-like freshwater algae was detected for the first time in the Lusitanian Basin, suggesting more restrictive conditions during the Late Oxfordian. During the Kimmeridgian, the amorphous material disappears and phytoclasts, mainly opaque phytoclasts, come to dominate the kerogen assemblage, as a result of terrigenous sediments input, due to the great proximity to the terrestrial source area.
•Palynofacies are reported for Gaiteiros-1 sedimentary sequence (Lusitanian Basin).•Monotonous carbonated record dominated by amorphous organic matter.•Non-carbonate sedimentation characterized by terrestrial organic matter.•Different depositional environments, from carbonate platform to fluvio-deltaic.•Coleochaete algae: first occurrence in the Jurassic fossil record.
A Wenlock (Silurian) sedimentary continuous sequence was sampled in the Dornes region (Central Iberian Zone, Portugal) to characterize the organic matter type using different microscopic analyses ...(organic petrology and palynofacies). Total organic carbon (TOC) was also determined. Samples are part of Foz da Sertã Formation and correspond to mudstone, punctually with sandstone, rich in organic matter (mean TOC value of 5.1%).
Whole rock samples showed a dominance of non-granular graptolites (lath- and blocky-shape) and solid bitumen. Lath-shape graptolites display the characteristic segmented structure. In the blocky-shape graptolites, the fusellar layers of the graptolite wall are well marked and are an important distinctive feature. Foz da Sertã graptolites are optically anisotropic as well as the solid bitumen. Non-granular graptolite's maximum reflectance varies from 1.43 to 3.94% and solid bitumen maximum reflectance oscillates between 1.09 and 2.22%. Vitrinite reflectance equivalent was calculated using Bertrand and Malo's equation (values between 1.97 and 3.72%) denoting a post-mature stage for the organic matter. No relation was established with confidence between graptolite maximum reflectance and solid bitumen maximum reflectance.
The palynofacies study confirmed not only the presence of graptolite and solid bitumen but also amorphous material derived from graptolite. Under transmitted white light, graptolite features were not noticed. To improve the palynofacies characterization, reflected white light was used on slides, thus exposing distinctive graptolite features. The different lights and preparation types used allowed a better characterization of the organic matter present in Foz da Sertã Formation samples, mainly the graptolites. The use of reflected white light, in the palynofacies study, proved to be extremely important in the description of the graptolite features.
•Silurian organic matter from Dornes region were studied.•Graptolites, amorphous particles and solid bitumen dominate the kerogen assemblage.•Organic matter are in a post-mature stage.•Reflected white light observation was essential to distinguishing graptolite features.
A new lectin from the marine sponge Chondrilla caribensis (CCL) was isolated by affinity chromatography in Sepharose 6B media. CCL is a homotetrameric protein formed by subunits of 15,445 ±2Da. The ...lectin showed affinity for disaccharides containing galactose and mucin. Mass spectrometric analysis revealed about 50% of amino acid sequence of CCL, which showed similarity with a lectin isolated from Aplysina lactuca. Secondary structure consisted of 10% α-helix, 74% β-sheet/β-turn and 16% coil, and this profile was unaltered in a broad range of pH and temperatures. CCL agglutinated Staphylococcus aureus, S epidermidis and Escherichia coli, and it was able to reduce biofilm biomass, but showed no inhibition of planktonic growth of these bacteria. CCL activity was inhibited by α-lactose, indicating that Carbohydrate Recognition Domain (CRD) of the lectin was involved in antibiofilm activity.
•The MBL2 -221 (X/YX) variant was associated with greater risk of DENV infection.•The LXPA haplotype, related to lower MBL levels, was exclusively found in dengue cases.•The frequency of MBL2 ...structural variants (O/AO) were higher in DENV-naïve children.•Serum levels of total and functional MBL were lower among DENV-infected children.
The mannose-binding lectin (MBL) plays an important role in innate immunity. Genetically determined variations in serum levels of MBL may influence the susceptibility and clinical outcome of dengue infection in early life.
We investigated the MBL2 gene polymorphisms and serum levels of MBL (total and functional) in children with asymptomatic (n=17) and symptomatic (n=29) primary dengue infections and age-matched uninfected children (n=84) enrolled in a birth cohort with dengue in Brazil. Polymorphisms of the MBL2 gene were assessed by reverse transcription-polymerase chain reaction (RT-PCR), whereas the enzyme-linked immunosorbent assay (ELISA) was used to quantify serum levels of MBL.
We found that the X allele and YX genotype in the MBL2 were more frequent in the dengue cases than in the control group. Likewise, the LXPA haplotype was exclusively found in dengue cases, thus probably related to dengue infection in our setting. Moreover, we found a higher frequency of the O allele and AO genotype in the control group. Serum levels of total and functional MBL were higher in dengue naïve infants than in dengue cases.
MBL2 variants related to lower production of serum MBL were associated with dengue infection in infants, whereas intermediate to high levels of total and functional serum MBL were associated with protection against dengue infection. These findings highlight the role of MBL2 variants and serum levels of MBL in the susceptibility of children to dengue disease at early ages.
The complex virulence attributes of Candida albicans are an attractive target to exploit in the development of new antifungals and anti-virulence strategies to combat C. albicans infections. ...Particularly, quorum sensing (QS) has been reported as critical for virulence regulation in C. albicans. This work presents two knowledge networks with up-to-date information about QS regulation and experimentally tested anti-QS and anti-virulence agents for C. albicans. A semi-automatic bioinformatics workflow that combines literature mining and expert curation was used to retrieve otherwise scattered information from the scientific literature. The network representation offers an innovative and continuously updatable means for the Candida research community to query QS and virulence data systematically and in a user-friendly way. Notably, the reconstructed networks show the complexity of QS regulation and the impact that some molecules have on the inhibition of virulence mechanisms responsible for infection establishment (e.g. hyphal development) and perseverance (e.g. biofilm formation). In the future, the compiled knowledge may be used to build decision-making models that help infer new knowledge of practical significance. The knowledge networks are publicly available at http://pcquorum.org/. This Web platform enables the exploration of fungal virulence cues as well as reported inhibitors in a user-friendly fashion.
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