Resumo em Inglês:

Abstract Polymorphic variants in the PTEN (rs2735343), PI3K (rs2699887), AKT1 (rs2494750), AR (rs17302090), and AMACR (rs3195676) genes were evaluated as possible molecular markers of susceptibility, prognosis, and progression of prostate cancer (PCa), in a case-control study. Samples consisted of 277 patients with PCa and 277 controls from Londrina, PR, Brazil. SNPs were analyzed by real-time PCR. A family history of cancer, including PCa, as well as level of schooling were risk factors for PCa. The data were obtained via logistic regression, using odds ratios with a CI 95%. The genotypes of AKT1 and AKT1+AR demonstrated an association with protection for the disease. The combination of SNPs with the histopathological tumor data between allele variants of AMACR, AKT1+AR, and AKT1+AMACR indicated an association with protection against seminal vesicle invasion. The polymorphisms AKT1+AR and PI3K+AR were associated with protection against tumor bilaterality. The genotype combinations PTEN+AMACR and PTEN+AR were associated with the risk of extracapsular extension. Of the five genes studied, two were associated with protection for PCa, four were associated with protection for some prognostic variables, and only one was associated with risk. Thus, these SNPs are candidates for markers to discriminate men with better or worse prognosis for PCa.

Resumo em Inglês:

Abstract MicroRNAs are considered as potential biomarkers, agents, or therapeutic targets; few studies have addressed the expression of miRNAs in treatment-naïve patients infected with HIV-1. The aim of this study was to assess plasma relative circulating miRNA expression profiles in treatment-naïve Mexican patients with HIV/AIDS and healthy individuals using a commercial array. A low CD4+ T cell count and high viral load were found in all patients. Decreased relative miRNA-296-5p expression was observed in patients; moreover, this was the only miRNA that showed differences between the two groups. Thus, we measured the absolute expression of miR-296-5p by qPCR, confirming the result with statistically significant differences (P < 0.05). There is evidence that miR-296-5p regulates the expression of the PIN1 gene, which encodes the peptidylprolyl Cis/Trans isomerase NIMA-Interacting-1, that is involved in different stages of the biological cycle of HIV-1, this relationship is corroborated by bioinformatics analysis and ELISA assay was used to measure plasma levels of PIN1. The decreased expression of miR-296-5p found in naïve patients with HIV infection suggests a regulatory activity of this miRNA on virus replication, making it a potential therapeutic agent against HIV. Finally, miR-296-5p could be inhibiting the virus transcription by regulating genes different than PIN1.

Resumo em Inglês:

Abstract Pemphigus is a group of autoimmune bullous skin diseases that result in significant morbidity. As for other multifactorial autoimmune disorders, environmental factors may trigger the disease in genetically susceptible individuals. The goals of this review are to summarize the state of knowledge about the genetic variation that may affect the susceptibility and pathogenesis of pemphigus vulgaris and pemphigus foliaceus – both the endemic and the sporadic forms –, to compare and discuss the possible meaning of the associations reported, and to propose recommendations for new research initiatives. Understanding how genetic variants translate into pathogenic mechanisms and phenotypes remains a mystery for most of the polymorphisms that contribute to disease susceptibility. However, genetic studies provide a strong foundation for further developments in this field by generating testable hypotheses. Currently, results still have limited influence on disease prevention and prognosis, drug development, and clinical practice, although the perspectives for future applications for the benefit of patients are encouraging. Recommendations for the continued advancement of our understanding as to the impact of genetic variation on pemphigus include these partially overlapping goals: (1) Querying the functional effect of genetic variants on the regulation of gene expression through their impact on the nucleotide sequence of cis regulatory DNA elements such as promoters and enhancers, the splicing of RNA, the structure of regulatory RNAs and proteins, binding of these regulatory molecules to regulatory DNA elements, and alteration of epigenetic marks; (2) identifying key cell types and cell states that are implicated in pemphigus pathogenesis and explore their functional genomes; (3) integrating structural and functional genomics data; (4) performing disease-progression longitudinal studies to disclose the causal relationships between genetic and epigenetic variation and intermediate disease phenotypes; (5) understanding the influence of genetic and epigenetic variation in the response to treatment and the severity of the disease; (6) exploring gene-gene and genotype-environment interactions; (7) developing improved pemphigus-prone and non-prone animal models that are appropriate for research about the mechanisms that link genotypes to pemphigus. Achieving these goals will demand larger samples of patients and controls and multisite collaborations.

Resumo em Inglês:

Abstract Citrullinemia type 1 (CTLNI), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), and mut0 methylmalonic acidemia (mut0 MMA) are inborn errors of metabolism (IEMs) associated with sudden unexpected death in infancy (SUDI). Its most common pathogenic variants are: c.1168G>A (CTLNI, ASS1 gene), c.1528G>C (LCHADD, HADHA gene), c.655A>T and c.1106G>A (mut0 MMA, MUT gene). Considering the absence of estimates regarding the incidence of these diseases in Brazil, this study sought to investigate the prevalence of its main pathogenic variants in a healthy population in the southern region of the country. A total of 1,000 healthy subjects from Rio Grande do Sul were included. Genotyping was performed by real-time PCR. Individuals found to be heterozygous for c.1528G>C underwent further acylcarnitine profile analysis by tandem mass spectrophotometry. Allele and genotype frequencies were calculated considering Hardy-Weinberg equilibrium. The c.1528G>C variant was detected in heterozygosity in two subjects (carrier frequency = 1:500; allele frequency = 0.001; minimum prevalence of LCHADD = 1: 1,000,000), whose acylcarnitine profiles were normal. Variants c.1168G>A, c.655A>T, and c.1106G>A were not identified. These results denote the rarity of these IEMs in Southern Brazil, highlighting the need to expand the investigation of IEMs in relation to infant morbidity and mortality within the country.

Resumo em Inglês:

Abstract ATP-Binding Cassette (ABC) transporters are involved in cholesterol metabolism and their dysfunctions could lead to obesity-associated complications. It was investigated whether SNPs in the ABCA1 (rs1800977 and rs2230806), ABCA7 (rs2279796) and ABCG1 (rs692383 and rs3827225) genes can modulate the responsiveness of 137 obese women to a weight-loss dietary intervention. Thus, anthropometric and lipid profiles were collected at baseline and after nine weeks of a calorie-restricted diet of 600kcal per day and participants were genotyped for the ABC genes SNPs. Regarding the transversal analysis, the ABCA7 rs2279796 GG genotype was associated with higher levels of total cholesterol and LDL-c at baseline (p = 0.044 for both). Association between ABCG1 rs692383 AA genotype and lower BMI were found in the post-diet moment, however, statistical significance was lost after multi-test correction. Regarding the longitudinal analysis, after multi-test correction, the association remained between ABCG1 rs692383 G allele and HDL-c levels: G allele carriers had a lower HDL-c reduction (p = 0.043). Results suggest the standard weight-loss diet applied in this study could attenuate the ABCA7 rs2279796 GG genotype effects found at baseline and non-dyslipidemic obese women with ABCG1 rs692383 G allele are benefitting from the diet with a lower reduction in HDL-c levels.

Resumo em Inglês:

Abstract The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. The mother aged 27 years-old presented progressive cerebellar ataxia, dysarthria, dysmetria, dysdiadochokinesis, limb ataxia and olivopontocerebellar atrophy. The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.

Resumo em Inglês:

Abstract Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.

Resumo em Inglês:

Abstract We present new karyotype records for six Proechimys species from the Brazilian Amazon. P. echinothrix from the region of Purus River had 2n = 32 chromosomes and a FN = 58, while P. cuvieri from the region of the Japurá River presented 2n = 28 and FN = 46. All individuals presented hybridization with an 18S rDNA probe in a single chromosome pair, with the exception of P. cuvieri from the Japurá region, which presented a third signal in one of the homologs of pair 1. No ITS were found in any of the individuals. Our data supports the hypothesis that the P. cuvieri population from the Japurá Basin and P. echinothrix from the lower Purus are new taxonomic entities. Our data expand the geographic distribution of the cytotype (2n = 40, FN = 54) described for P. gardneri from the Madeira River, and the cytotype (2n = 46, FN = 50), described for P. guyannensis, as well as the recently-described cytotype of P. goeldii (2n = 16, FN = 14). No clear pattern of chromosomal evolution has yet been defined in Proechimys, despite the considerable karyotypic diversity of the genus.

Resumo em Inglês:

Abstract The grasshopper Rhammatocerus brasiliensis shows polymorphism of B chromosomes, but the magnitude of B-chromosome occurrence and the factors that may contribute to their dispersion in the species remain unknown thus far. The present study analyzed the occurrence and dispersion of B chromosomes in R. brasiliensis individuals from 21 populations widely distributed in the Brazilian Northeast. The genetic connectivity between 10 populations was verified through analysis of ISSR markers from 200 individuals. Of the 21 populations, 19 presented individuals with one B chromosome, three with two, and one with three B chromosomes. The B chromosome is of medium size and constitutive heterochromatin (CH) located in the pericentromeric region. A variant B chromosome was observed in three populations, similar in size to that of chromosome X, gap and CH, and located in the terminal region. B chromosome frequencies in different populations varied from 0% to 18,8%, mean 8,5%. The wide distribution of the B chromosome is likely a consequence of the positive gene flow among the analyzed populations. B-chromosome occurrence in populations of R. brasiliensis possibly follows the population genetic structure of the species and, owing to the existence of a variant, its origin may not be recent.

Resumo em Inglês:

Abstract Cytogenetic analyses of the Suboscines species are still scarce, and so far, there is no karyotype description of any species belonging to the family Conopophagidae. Thus, the aim of this study is to describe and analyze the karyotype of Conopophaga lineata by chromosome painting using Gallus gallus (GGA) probes and to identify the location of the 18/28S rDNA cluster. Metaphases were obtained from fibroblast culture from two individuals of C. lineata. We observed a diploid number of 2n=78. GGA probes showed that most ancestral syntenies are conserved, except for the fission of GGA1 and GGA2, into two distinct pairs each. We identified the location of 18S rDNA genes in a pair of microchromosomes. The fission of the syntenic group corresponding to GGA2 was observed in other Furnariida, and hence may correspond to a chromosomal synapomorphy for the species of Parvorder Furnariida.

Resumo em Inglês:

Abstract Fish eggs are often excluded from identification analysis since at this stage of development there are few morphological characters. The correct identification of eggs can provide important information about spawning areas of species. The current work aimed to identify fish eggs in the Tibagi and Cinzas Rivers using the DNA barcode to obtain information on richness and diversity, adding to the existing data in the area. Of the 928 sequences analyzed using the BOLD Systems database, 99.78% were able to be identified at a specific level, demonstrating a high success rate for egg identification. The samples resulted in 25 species, 11 families, and 2 orders. Of the 25 species found, more than half (60%) present reproductive migration behavior, indicating that the tributaries of the Capivara reservoir are being used as a migratory route by these species. Eggs of rare and endangered species were found, indicating these tributaries as spawning grounds for these species. The results demonstrate the importance of identifying fish eggs in reservoir-influenced environments to recognize breeding areas of native and endangered species, as well as the importance of the Tibagi and Cinzas Rivers for the maintenance of native fish species in the Paranapanema River.

Resumo em Inglês:

Abstract Cytogenetics can be a useful tool to assist in taxonomic problems by adding information to the widely used morphological and molecular approaches. These taxonomic problems are especially common in anurans, once they are very diverse, highly polymorphic, and present many cryptic species. The genus Thoropa Cope, 1865 is composed of six specialist species that reproduce in rocky outcrops and are distributed throughout the Atlantic Forest and Cerrado ecotones. Phylogenetic studies point to possible cryptic species within the T. miliaris group. To assist in the evolutionary and taxonomic understanding of this group, classical cytogenetic techniques were used to find possible molecular markers for the genus through rDNA5S, rDNA18S, and U2snDNA probes and analyze their chromosome distribution in the group of T. miliaris. Despite the well conserved karyotype under conventional staining and classical techniques, such as Ag-NOR, our C-banding results showed differences in the centromeric heterochromatin concentration between two populations of T. miliaris. Furthermore, some differences among the populations and species were found for rDNA5S and U2snDNA. This study contributes to a better understanding of the evolutionary relationships within the genus; however, the use of different probe sequences, such as satDNA, is essential for a more robust cytogenetic analysis.

Resumo em Inglês:

Abstract Cross-species hybridizations have been extensively used to generate animals and plants better suited for draft and food and fiber production since Roman times, and are still important in current agricultural practices with growing uses especially in aquaculture. Diagnostic tools based on marker panels with sufficient numbers of markers for accurate identification of cross-species hybrid individuals from intercrossed and backcrossed populations are increasingly necessary for practical, accurate species-purity certification and management of commercial broodstocks. Minimal numbers of di-allelic markers with species-specific alleles required to accurately identify hybrid individuals in intercrossed and advanced backcrossed populations were estimated using power analysis, and ranged from 5 to 191 (α = .05), and from 7 to 293 (α = .01), considering backcross 1 (BC1) to BC6 populations, respectively. Numbers of markers required for accurate hybrid identification observed in simulated BC1 to BC6 populations ranged from 5 to 1,131 and 7 to 8,065, considering error rates ≤ 5% and ≤ 1%, respectively. Estimated and observed numbers of diagnostic markers required for accurate hybrid identification up to four generations of backcrossing fall within practical operational limits of most commercial platforms currently available for genotyping low-density SNP marker panels. Therefore, cost-effective assay panels could be developed to provide practical tools for accurate species-purity certification.

Resumo em Inglês:

Abstract Brazil has five climatically distinct regions, with an annual average temperature difference up to 14 ºC between the northern and southern extremes. Environmental variation of this magnitude can lead to new genetic patterns among farmed fish populations. Genetically differentiated populations of tambaqui (Colossoma macropomum Cuvier, 1818), an important freshwater fish for Brazilian continental aquaculture, may be associated with regional adaptation. In this study, we selected tambaquis raised in two thermally distinct regions, belonging to different latitudes, to test this hypothesis. De novo transcriptome analysis was performed to compare the significant differences of genes expressed in the liver of juvenile tambaqui from a northern population (Balbina) and a southeastern population (Brumado). In total, 2,410 genes were differentially expressed (1,196 in Balbina and 1,214 in Brumado). Many of the genes are involved in a multitude of biological functions such as biosynthetic processes, homeostasis, biorhythm, immunity, cell signaling, ribosome biogenesis, modification of proteins, intracellular transport, structure/cytoskeleton, and catalytic activity. Enrichment analysis based on biological networks showed a different protein interaction profile for each population, whose encoding genes may play potential functions in local thermal adaptation of fish to their respective farming environments.

Resumo em Inglês:

Abstract Water deficit is an important climatic problem that can impair agriculture yield and economy. Genetically modified soybean plants containing the AtNCED3 gene were obtained aiming drought-tolerance improvement. The NCED3 gene encodes a 9-cis-epoxycarotenoid dioxygenase (NCED, EC 1.13.11.51), an important enzyme in abscisic acid biosynthesis. ABA activates the expression of drought-responsive genes, in water-deficit conditions, targeting defense mechanisms and enabling plants to survive under low water availability. Results from greenhouse experiments showed that the transgene AtNCED3 and the endogenous genes GmAREB1, GmPP2C, GmSnRK2 and GmAAO3 presented higher expression under water deficit (WD) in the event 2Ha11 than in WT-plants. No significant correlation was observed between the plant materials and WD conditions for growth parameters; however, gas exchange measurements decreased in the GM event, which also showed 80% higher intrinsic water use when compared to WT plants. In crop season 2015/16, event 2Ha11 showed higher total number of pods, higher number of pods with seeds and yield than WT plants. ABA concentration was also higher in GM plants under WD. These results obtained in field screenings suggest that AtNCED3 soybean plants might outperform under drought, reducing economic and yield losses, thus being a good candidate line to be incorporated in the soybean-breeding program to develop drought-tolerant cultivars.

Resumo em Inglês:

Abstract The genome size varies widely among angiosperms but only a few clades present huge variation at a low phylogenetic level. Among diploid species of the genus Cuscuta the genome size increased enormously in at least two independent lineages: in species of subgenus Monogynella and in at least one species (C. indecora) of the subgenus Grammica. Curiously, the independent events lead to similar karyotypes, with 2n = 30 mostly metacentric chromosomes. In this paper we compared the patterns of heterochromatic bands and rDNA sites of C. indecora and C. monogyna, aiming to evaluate the role of these repetitive fractions in these karyotypes. We found out that the large genomes of these species were incremented by a huge number of small heterochromatic CMA+ and DAPI+ bands and 5S and 35 rDNA sites, most of them clearly colocalized with CMA+ bands. Silver nitrate impregnation revealed that the maximum number of nucleoli per nucleus was low in both species, suggesting that some of these sites may be inactive. Noteworthy, the tandem repeats did not generate large bands or sites but rather dozens of small blocks dispersed throughout the chromosomes, apparently contributing to conserve the original karyotype symmetry.

Resumo em Inglês:

Abstract - Growth Regulating Factors (GRFs) comprise a transcription factor family with important functions in plant growth and development. They are characterized by the presence of QLQ and WRC domains, responsible for interaction with proteins and DNA, respectively. The QLQ domain is named due to the similarity to a protein interaction domain found in the SWI2/SNF2 chromatin remodeling complex. Despite the occurrence of the QLQ domain in both families, the divergence between them had not been further explored. Here, we show evidence for GRF origin and determined its diversification in angiosperm species. Phylogenetic analysis revealed 11 well-supported groups of GRFs in flowering plants. These groups were supported by gene structure, synteny, and protein domain composition. Synteny and phylogenetic analyses allowed us to propose different sets of probable orthologs in the groups. Besides, our results, together with functional data previously published, allowed us to suggest candidate genes for engineering agronomic traits. In addition, we propose that the QLQ domain of GRF genes evolved from the eukaryotic SNF2 QLQ domain, most likely by a duplication event in the common ancestor of the Charophytes and land plants. Altogether, our results are important for advancing the origin and evolution of the GRF family in Streptophyta.

Resumo em Inglês:

Abstract Transcription factors play an important role in fungal environmental adaptive process by promoting adjustment to challenging stimuli via gene modulation and activation of signaling networks. The transcription factor encoded by the pac-3/rim101/pacC gene is involved in pH regulation and is associated with a wide variety of cellular functions. The deletion of pac-3 affects fungal development. In Neurospora crassa, the Δpac-3 strain presents diminished aerial growth and reduced conidiation. However, the PAC-3-regulated genes associated with this altered phenotype have not been elucidated. In this study, we used RNA-seq to analyze the phenotypic plasticity induced after pac-3 deletion in the filamentous fungus N. crassa cultivated in media supplemented with sufficient or limited inorganic phosphate. Genes related to morphology, hyphal development, and conidiation were of particular interest in this study. Our results suggest a pac-3 dependency in gene regulation in a Pi-dependent manner. Furthermore, our analysis suggested that the fungus attempts to overcome the deletion effects in a Δpac-3 mutant through a complex combined regulatory mechanism. Finally, the modulatory responses observed in the Δpac-3 strain, a double mutant generated based on the Δmus-52 mutant strain, is strain-specific, highlighting that the phenotypic impact may be attributed to pac-3 absence despite the combined mus-52 deletion.

Resumo em Inglês:

Abstract Cell cycle alterations are among the principle hallmarks of cancer. Consequently, the study of cell cycle regulators has emerged as an important topic in cancer research, particularly in relation to environmental exposure. Particulate matter and coal dust around coal mines have the potential to induce cell cycle alterations. Therefore, in the present study, we performed chemical analyses to identify the main compounds present in two mineral coal samples from Colombian mines and performed systems chemo-biology analysis to elucidate the interactions between these chemical compounds and proteins associated with the cell cycle. Our results highlight the role of oxidative stress generated by the exposure to the residues of coal extraction, such as major inorganic oxides (MIOs), inorganic elements (IEs) and polycyclic aromatic hydrocarbons (PAH) on DNA damage and alterations in the progression of the cell cycle (blockage and/or delay), as well as structural dysfunction in several proteins. In particular, IEs such as Cr, Ni, and S and PAHs such as benzo[a]pyrene may have influential roles in the regulation of the cell cycle through DNA damage and oxidative stress. In this process, cyclins, cyclin-dependent kinases, zinc finger proteins such as TP53, and protein kinases may play a central role.

Resumo em Inglês:

Abstract Dietary phenolic compounds such as caffeic and chlorogenic acid exert an antiproliferative effect and modulate the gene-specific DNA methylation status in human breast tumor cells, but it remains unclear whether they interfere with global DNA methylation in human leukemia cells. We examined whether caffeic and chlorogenic acid (1-250 µM) exert antitumor action in human promyelocytic leukemia cells (HL-60) and human acute T-cell leukemia cells (Jurkat). Caffeic and chlorogenic acid did not reduce cell viability in the two cell lines, as assessed using the neutral red uptake and MTT assays. These phenolic acids (1-100 μM) neither induced DNA damage (comet assay) nor increased the micronuclei frequency (micronucleus assay) in HL-60 and Jurkat cells, indicating that they were not genotoxic or mutagenic. Analysis of global DNA methylation levels using a 5-mC DNA ELISA kit revealed that chlorogenic acid at a non-cytotoxic concentration (100 μM) induced global DNA hypomethylation in Jurkat cells, but not in HL-60 cells, suggesting that it exerts a cell-specific effect. Caffeic acid did not change global DNA methylation. As other phenolic compounds, chlorogenic acid probably modulates DNA methylation by targeting DNA methyltransferases. The hypomethylating action of chlorogenic acid can be beneficial against hematological malignances whose pathogenic processes involve impairment of DNA methylation.

Resumo em Inglês:

Abstract Rabies is a fatal zoonotic infection of the central nervous system of mammals and has been known to humans for millennia. The etiological agent, is a neurotropic RNA virus in the order Mononegavirales, family Rhabdoviridae, genus Lyssavirus. There are currently accepted to be two cycles for rabies transmission: the urban cycle and the sylvatic cycle. The fact that both cycles originated from a common RABV or lyssavirus ancestor and the adaptive divergence that occurred since then as this ancestor virus adapted to a wide range of fitness landscapes represented by reservoir species in the orders Carnivora and Chiroptera led to the emergence of the diverse RABV lineages currently found in the sylvatic and urban cycles. Here we study full genome phylogenies and the time to the most recent common ancestor (TMRCA) of the RABVs in the sylvatic and urban cycles. Results show that there were differences between the nucleotide substitution rates per site per year for the same RABV genes maintained independently in the urban and sylvatic cycles. The results identify the most suitable gene for phylogenetic analysis, heterotachy among RABV genes and the TMRCA for the two cycles.

Resumo em Inglês:

Abstract Bone infection or osteomyelitis is usually a complication of inflammation-related traumatic bone injury. Selenium has been shown to have potential cytoprotective effects and the ability to reduce oxidative stress and apoptotic events in osteomyelitis, but the exact mechanism remains unclear. Here, we used LPS-induced apoptotic MC3T3-E1 cells and aimed to confirm selenium's protective effect on cell apoptosis as well as to investigate the underlying mechanisms of this role. Our investigation confirmed selenium-mediated inhibition of LPS-induced cell apoptosis and ROS accumulation in MC3T3-E1 cells. Upon selenium treatment, the bcl-2 levels were upregulated, while the levels of Bax and cyto-C were down-regulated. Furthermore, these effects were accompanied by the suppression of miR-155 and the phosphorylation of protein kinase B (Akt). A more in-depth study demonstrated that LY294002 (a specific inhibitor of PI3K), abolished the selenium-mediated cytoprotective effect of MC3T3-E1 cells against LPS-induced injury and down-regulation of miR-155. In general, these results demonstrated that selenium exerts a cytoprotective effect by attenuating cell apoptosis and oxidative damage via a PI3K/Akt/miR-155-dependent mechanism.

Resumo em Inglês:

Abstract Coronary heart disease (CHD) is a leading cause of death worldwide, and angiogenesis plays important roles in CHD. Thus, in the present study, the angiogenic efficacy of four common cardiovascular medicines (aspirin, pravastatin, metoprolol and isosorbide mononitrate (ISMN)) was determined by the number and length of zebrafish intersegmental vessels (ISVs) after immersing zebrafish embryos in different medicines. Results showed that ISMN significantly increased the length and number of ISVs. ISMN is a long-acting nitrate ester drug. It has been used as a vasodilator to dilate arteries and veins to reduce the cardiac preload and postload. However, the effect of ISMN on angiogenesis remains unclear. Thus, by in vitro experiments, the angiogenic mechanism of ISMN was evaluated through detecting the viability and proliferation of human umbilical vein endothelial cells (HUVECs) and the expression of angiogenesis-related genes and miRNAs. Results indicated that ISMN could increase the viability and proliferation of HUVECs by decreasing apoptosis, and elevated the expressions of vedf, kdrl, pdgfr in zebrafish embryos. Furthermore, the expressions of miR-126, miR-130a and miR-210 were also regulated in ISMN-treated HUVECs. In conclusion, ISMN could promote angiogenesis in zebrafish embryos and HUVECs, implying ISMN may be a potential therapeutic in treating angiogenesis-related diseases.

Resumo em Inglês:

Abstract Despite considerable advances, the treatment of pancreatic cancer (PC) still requires much effort. Unusual regulation of the Wnt and apoptotic signaling pathways is widespread in cancer incidence. For instance, the WIF1 (Wnt inhibitory factor 1) gene is down-regulated in many cancers. The purpose of this study was to determine the effects of recombinant Betatrophin, a recently discovered hormone, on MiaPaca-II and Panc-1 pancreatic cell lines. Various concentrations of Betatrophin were added to MiaPaca-II and Panc-1 pancreatic cell lines during periods of 24 , 48, and 72 h. The MTT assay was applied to investigate cell proliferation after treatment. The rate of apoptotic cells was assessed using double-staining flow cytometry, and the expression levels of the WIF1 gene and Bcl2 protein was observed by real-time PCR and western blotting, respectively. The findings of this study suggest that Betatrophin has an anti-proliferative effect on both MiaPaca-II and Panc-1 cell lines, in line with the up-regulation of WIF1 as a tumor suppressor gene. Moreover, the induction of apoptosis by ANGPTL8 occurred by the down-regulation of Bcl2. Thus, Betatrophin can be proposed as a potential therapeutic drug for treating pancreatic cancer.

Resumo em Inglês:

Abstract Lung cancer has one of the highest mortality rates of malignant neoplasms. Lung adenocarcinoma (LUAD) is one of the most common types of lung cancer. DNA methylation is more stable than gene expression and could be used as a biomarker for early tumor diagnosis. This study is aimed to screen potential DNA methylation signatures to facilitate the diagnosis and prognosis of LUAD and integrate gene expression and DNA methylation data of LUAD to identify functional epigenetic modules. We systematically integrated gene expression and DNA methylation data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), bioinformatic models and algorithms were implemented to identify signatures and functional modules for LUAD. Three promising diagnostic and five potential prognostic signatures for LUAD were screened by rigorous filtration, and our tumor-normal classifier and prognostic model were validated in two separate data sets. Additionally, we identified functional epigenetic modules in the TCGA LUAD dataset and GEO independent validation data set. Interestingly, the MUC1 module was identified in both datasets. The potential biomarkers for the diagnosis and prognosis of LUAD are expected to be further verified in clinical practice to aid in the diagnosis and treatment of LUAD.

Resumo em Inglês:

Abstract Wickerhamomyces anomalus LBCM1105 is a yeast isolated from cachaça distillery fermentation vats, notable for exceptional glycerol consumption ability. We report its draft genome with 20.5x in-depth coverage and around 90% extension and completeness. It harbors the sequences of proteins involved in glycerol transport and metabolism.

Resumo em Inglês:

Abstract Bletilla striata polysaccharide (BSP) is the main component of Bletilla striata, which has important pharmacological and pharmacological effects; however, due to the lack of genetic data, the metabolic pathways of BSP remain unclear. For this study, 11 representative resources of B. striata were analyzed, and the BSP contents of the different samples were significantly different; however, the monosaccharide composition of BSP was glucose and mannose. The representative samples were selected to observe their life history in situ, which were then divided and cultured in a greenhouse. Finally, samples from various organs of different plants were combined for transcriptome sequencing using the Illumina system. Our results summarized the BSP metabolic pathway, and we found that there were eight enzyme genes involved in biosynthesis, but these genes showed tissue specificity. Following qRT-PCR validation and comparative analysis, manA showed the highest expression; however, there were significant differences between the two germplasm resources in which the BSP content was significantly different, while UGP2, GPI, PMM, and GMPP had significant differences between the two samples. In summary, this study lays the foundation for further research into BSP metabolism and other physiological processes at the molecular level.

Resumo em Inglês:

Abstract Papaver setigerum is an annual herb that is closely related to the opium poppy, P. somniferum. Genetic resources for P. setigerum are scarce. In the present study, we assembled the complete chloroplast (cp) genome of P. setigerum based on genome skimming data, and we conducted comparative cp genome analyses to study the evolutionary pattern in Papaveraceae. The cp genome of P. setigerum is 152,862 bp in length with a typical quadripartite structure. Comparative analyses revealed no gene rearrangement in the Papaveraceae family, although differences were evident in genome size, gene losses, as well as inverted repeats (IR) region expansion and contraction. The rps15 gene has been lost from the genomes of Meconopsis racemosa, Coreanomecon hylomeconoides, P. orientale, P. somniferum, and P. setigerum, and the ycf15 gene is found only in C. hylomeconoides. Moreover, 13 cpDNA markers, including psbA-trnH, rps16-trnQ, trnS-trnG, trnC-petN, trnE-trnT, trnL-trnF, trnF-ndhJ, petA-psbJ, ndhF-rpl32, rpl32-trnL, ccsA-ndhD, ndhE-ndhG, and rps15-ycf1, were identified with relatively high levels of variation within Papaver, which will be useful for species identification in this genus. Among those markers, psbA-trnH is the best one to distinguish P. somniferum and P. setigerum.