Regarding the development of new antineoplastic agents, with a view to assess the selective antitumoral potential which aims at causing irreversible damage to cancer cells while preserving the ...integrity of their healthy counterparts, it is essential to evaluate the cytotoxic effects in both healthy and malignant human cell lines. In this study, a complex with two Pd(II) centers linked by the biogenic polyamine spermine (Pd2Spm) was tested on healthy (PNT-2) and cancer (LNCaP and PC-3) prostate human cell lines, using cisplatin as a reference. To understand the mechanisms of action of both cisplatin and Pd2Spm at a molecular level, Fourier Transform Infrared (FTIR) and Raman microspectroscopies were used. Principal component analysis was applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug impact. The main changes were observed between the B-DNA native conformation and either Z-DNA or A-DNA, with a higher effect on lipids having been detected in the presence of cisplatin as compared to Pd2Spm. In turn, the Pd-agent showed a more significant impact on proteins.
In Colombia, coffee growers use a traditional method of fermentation to remove the cherry pulp surrounding the beans. This process has a great influence on sensory quality and prestige of Colombian ...coffee in international markets, but has never been studied. Here we use an Illumina-based amplicon sequencing to investigate bacterial and fungal communities associated with spontaneous coffee-bean fermentation in Colombia. Microbial-derived metabolites were further analysed by high-performance liquid chromatography and gas chromatography-mass spectrometry. Highly diverse bacterial groups, comprising 160 genera belonging to 10 phyla, were found. Lactic acid bacteria (LAB), mainly represented by the genera Leuconostoc and Lactobacillus, showed relative prevalence over 60% at all sampling times. The structure of the fungal community was more homogeneous, with Pichia nakasei dominating throughout the fermentation process. Lactic acid and acetaldehyde were the major end-metabolites produced by LAB and Pichia, respectively. In addition, 20 volatile compounds were produced, comprising alcohols, organic acids, aldehydes, esters, terpenes, phenols, and hydrocarbons. Interestingly, 56 microbial genera, associated with native soil, seawater, plants, insects, and human contact, were detected for the first time in coffee fermentation. These microbial groups harbour a remarkable phenotypic diversity and may impart flavours that yield clues to the terroir of Colombian coffees.
Histone modifications establish the chromatin states that coordinate the DNA damage response. In this study, we show that SETD2, the enzyme that trimethylates histone H3 lysine 36 (H3K36me3), is ...required for ATM activation upon DNA double-strand breaks (DSBs). Moreover, we find that SETD2 is necessary for homologous recombination repair of DSBs by promoting the formation of RAD51 presynaptic filaments. In agreement, SETD2-mutant clear cell renal cell carcinoma (ccRCC) cells displayed impaired DNA damage signaling. However, despite the persistence of DNA lesions, SETD2-deficient cells failed to activate p53, a master guardian of the genome rarely mutated in ccRCC and showed decreased cell survival after DNA damage. We propose that this novel SETD2-dependent role provides a chromatin bookmarking instrument that facilitates signaling and repair of DSBs. In ccRCC, loss of SETD2 may afford an alternative mechanism for the inactivation of the p53-mediated checkpoint without the need for additional genetic mutations in TP53.DOI: http://dx.doi.org/10.7554/eLife.02482.001.
Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, ...which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
Oropharyngeal cancer is an important public health problem. The aim of our study was to correlatep16 immunohistochemistry in oropharynx squamous cell carcinomas(OPSCC) with clinical and ...epidemiological features.
We conducted across-sectional study on patients with OPSCC treated at a single institution from 2014 to 2019. Epidemiological and clinical-pathological data were collected from medical records and a questionnaire was applied to determine alcohol consumption, smoking, and sexual behavior. The HPV status was determined by p16 immunohistochemistry.
A total of 252 patients participated in the study, of these 221 (87.7%) were male. There were 81 (32.14%) p16 positive cases and 171 (67.85%) p16 negative cases. The p16positive group was significantly associated with younger patients (50-59 years), higher education level, lower clinical stage and patients who never drank or smoked. Through univariate logistic regression, we observed that female sex (OR, 3.47; 95% CI, 1.60-7.51) and higher education level (OR, 9.39; 95% CI, 2, 81-31,38) were significantly more likely to be p16 positive. Early clinical stage (AJCC8ed) was more associated with p16 positivity both in univariate (OR, 0.14; 95% CI, 0.07-0.26, p<0.001) and multivariate analysis (OR, 0.18; 95% CI, 0.06-0.49, p = 0.001).
This study showed that drinkers and current smokers were less likely to be p16+. Female sex, higher education level and younger age at diagnosis were associated with a higher probability of being p16+. Additionally, there was a higher proportion of patients with early clinical stage (I or II) in the p16 positive group when compared to the p16 negative group.
Starter cultures are defined as selected microbial preparations used to increase the efficiency of fermentation processes. In the food industry, numerous microbial cultures are used to ensure the ...production of safe and high-quality commodities. This review provides a comprehensive theoretical guide for selecting microbial cultures for use in the manufacturing of industrially important food commodities, including dairy, meat, vegetables, alcoholic beverages, cocoa, coffee, vinegar, and soy-based products. Related topics on fermented food classification, microbial domestication, and regulatory requirements are addressed. The strategies reported in this review are useful to help researchers choose methods and criteria selection.
Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is ...evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti-inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan-induced paw edema and myeloperoxidase activity in the paw skin. The anti-inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-α and IL-1β. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation.
Noisy data are common in real-world problems and may have several causes, like inaccuracies, distortions or contamination during data collection, storage and/or transmission. The presence of noise in ...data can affect the complexity of classification problems, making the discrimination of objects from different classes more difficult, and requiring more complex decision boundaries for data separation. In this paper, we investigate how noise affects the complexity of classification problems, by monitoring the sensitivity of several indices of data complexity in the presence of different label noise levels. To characterize the complexity of a classification dataset, we use geometric, statistical and structural measures extracted from data. The experimental results show that some measures are more sensitive than others to the addition of noise in a dataset. These measures can be used in the development of new preprocessing techniques for noise identification and novel label noise tolerant algorithms. We thereby show preliminary results on a new filter for noise identification, which is based on two of the complexity measures which were more sensitive to the presence of label noise.
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