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•A variety of approaches for the extraction of lipids from microalgae were reviewed.•The bioactivity of microalgae lipids is summarized.•Innovative techniques have advantages in ...improving yield and reducing pollution.
Microalgae, as a photosynthetic autotrophic organism, contain a variety of bioactive compounds, including lipids, proteins, polysaccharides, which have been applied in food, medicine, and fuel industries, among others. Microalgae are considered a good source of marine lipids due to their high content in unsaturated fatty acid (UFA) and can be used as a supplement/replacement for fish-based oil. The high concentration of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) in microalgae lipids, results in important physiological functions, such as antibacterial, anti-inflammatory, and immune regulation, being also a prerequisite for its development and application. In this paper, a variety of approaches for the extraction of lipids from microalgae were reviewed, including classical and innovative approaches, being the advantages and disadvantages of these methods emphasized. Further, the effects of microalgae lipids as high value bioactive compounds in human health and their use for several applications are dealt with, aiming using green(er) and effective methods to extract lipids from microalgae, as well as develop and extend their application potential.
Metal-organic frameworks (MOFs) based on high-connected nets are generally very attractive due to their combined robustness and porosity. Here, we describe the synthesis of BCN-348, a new ...high-connected Zr-MOF built from an 8-connected (8-c) cubic Zr-oxocluster and an 8-c organic linker. BCN-348 contains a minimal edge-transitive 3,4,8-c eps net, and combines mesoporosity with thermal and hydrolytic stability. Encouraging results from preliminary studies on its use as a catalyst for hydrolysis of a nerve-agent simulant suggest its potential as an agent for detoxification of chemical weapons and other pernicious compounds.
We present BCN-348, a new high-connected MOF built from an 8-c cubic Zr-oxocluster and an 8-c organic linker. BCN-348 shows a 3,4,8-c eps net, mesoporosity, hydrolytic stability, and acts as a catalyst for hydrolysis of a nerve-agent simulant.
Meat constitutes one the main protein sources worldwide. However, ethical and health concerns have limited its consumption over the last years. To overcome this negative impact, new ingredients from ...natural sources are being applied to meat products to obtain healthier proteinaceous meat products. Algae is a good source of unsaturated fatty acids, proteins, essential amino acids, and vitamins, which can nutritionally enrich several foods. On this basis, algae have been applied to meat products as a functional ingredient to obtain healthier meat-based products. This paper mainly reviews the bioactive compounds in algae and their application in meat products. The bioactive ingredients present in algae can give meat products functional properties such as antioxidant, neuroprotective, antigenotoxic, resulting in healthier foods. At the same time, algae addition to foods can also contribute to delay microbial spoilage extending shelf-life. Additionally, other algae-based applications such as for packaging materials for meat products are being explored. However, consumers' acceptance for new products (particularly in Western countries), namely those containing algae, not only depends on their knowledge, but also on their eating habits. Therefore, it is necessary to further explore the nutritional properties of algae-containing meat products to overcome the gap between new meat products and traditional products, so that healthier algae-containing meat can occupy a significant place in the market.
The RNA modification N6-methyladenosine (m6A) post-transcriptionally regulates RNA function. The cellular machinery that controls m6A includes methyltransferases and demethylases that add or remove ...this modification, as well as m6A-binding YTHDF proteins that promote the translation or degradation of m6A-modified mRNA. We demonstrate that m6A modulates infection by hepatitis C virus (HCV). Depletion of m6A methyltransferases or an m6A demethylase, respectively, increases or decreases infectious HCV particle production. During HCV infection, YTHDF proteins relocalize to lipid droplets, sites of viral assembly, and their depletion increases infectious viral particles. We further mapped m6A sites across the HCV genome and determined that inactivating m6A in one viral genomic region increases viral titer without affecting RNA replication. Additional mapping of m6A on the RNA genomes of other Flaviviridae, including dengue, Zika, yellow fever, and West Nile virus, identifies conserved regions modified by m6A. Altogether, this work identifies m6A as a conserved regulatory mark across Flaviviridae genomes.
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•The RNA genomes of HCV, ZIKV, DENV, YFV, and WNV contain m6A modification•The cellular m6A machinery regulates HCV infectious particle production•YTHDF proteins reduce HCV particle production and localize at viral assembly sites•m6A-abrogating mutations in HCV E1 increase infectious particle production
N6-methyladenosine (m6A) post-transcriptionally regulates RNA function. Gokhale et al. demonstrate that the RNA genomes of HCV, ZIKV, DENV, YFV, and WNV are modified by m6A. Depletion of cellular machinery that regulates m6A or introduction of m6A-abrogating mutations within HCV RNA increase viral particle production, suggesting that m6A negatively regulates HCV.
Abstract
Background
Most Crohn’s disease CD patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impacts of ileocolectomy-induced bile ...acid BA perturbations on intestinal microbiota and inflammation are unknown. We characterized the relationships between ileocolectomy, stool BAs, microbiota and intestinal inflammation in inflammatory bowel disease IBD.
Methods
Validated IBD clinical and endoscopic assessments were prospectively collected. Stool primary and secondary BA concentrations were compared based on ileocolectomy and ileitis status. Primary BA thresholds for ileitis were evaluated. Metagenomic sequencing was use to profile microbial composition and function. Relationships between ileocolectomy, BAs and microbiota were assessed.
Results
In 166 patients, elevated primary and secondary BAs existed with ileocolectomy. With ileitis, only primary BAs 795 vs 398 nmol/g, p = 0.009 were higher compared to without ileitis. The optimal primary BA threshold ≥228 nmol/g identified ileitis on multivariable analysis odds ratio = 2.3, p = 0.04. Microbial diversity, Faecalibacterium prausnitzii and O-acetylhomoserine aminocarboxypropyltransferase MetY were decreased with elevated primary BAs. Amongst ileocolectomy patients, only those with elevated primary BAs had diversity, F. prausnitzii and MetY reductions. Those with both ileocolectomy and intermediate p = 0.002 or high ≥228 nmol/g, p = 9.1e-11 primary BA concentrations had reduced F. prausnitzii compared to without ileocolectomy. Those with ileocolectomy and low <29.2 nmol/g primary BA concentrations had similar F. prausnitzii to those without ileocolectomy p = 0.13. MetY was reduced with ileitis p = 0.02.
Conclusions
Elevated primary BAs were associated with ileitis, and reduced microbial diversity, F. prausnitzii abundance and enzymatic abundance of MetY acetate and l-methionine-producing enzyme expressed by F. prausnitzii, and were the only factors associated with these findings after ileocolectomy.
Diet is a fundamental aspect of the ecological niche of amphibians and usually varies intra-specifically in response to extrinsic environmental and intrinsic individual factors. Phenotypic variations ...among individuals can generate intrapopulation differences in trophic resource use, which could have important ecological and evolutionary implications in amphibian populations. Here, we studied the intrapopulation dietary variation of the frog Pseudopaludicola pusilla in an anthropic savanna of the Colombian Caribbean region, considering the effects of seasonality and sex on the size, amount, prey composition and dietary individual specialization. We collected 44 adult frogs during the dry season and 46 during the rainy season and analyzed their stomach contents to determine their dietary composition. Our results indicate that P. pusilla is a generalist and opportunist predator, feeding mainly on insects of the orders Orthoptera, Coleoptera and Hymenoptera, which were the most important prey categories due to their numeric, volumetric and frequency contributions. We observed seasonal variations regarding volumetric prey composition and the importance value of each prey category in the populational diet. Individuals of P. pusilla consume more prey items during the rainy season and bigger prey during the dry season, but the volume of stomach contents did not vary seasonally. Males and females of P. pusilla consumed a similar number of prey items, but females ingested more voluminous prey and had greater volumes of stomach contents than males. Additionally, we observed a pattern of dietary individual specialization, which was not related to morphological trade-offs and did not differ among seasons. These findings contribute to the understanding of the seasonal dynamics of the use of trophic resources by anurans and the effect of sex on dietary characteristics of P. pusilla, in environments strongly influenced by climatic seasonality.
Despite improvements in the treatment options, acute myeloid leukemia (AML) remains a fatal malignancy with an estimated 5-year relative survival rate of 31.7%. There is continued need for ...identification of new disease drivers to develop novel therapeutic options and improve clinical outcomes. Dysregulated transcriptional landscapes are associated with disease pathogenesis and treatment responses. To identify new disease drivers of AML, we analyzed RNA-Seq data from 59 patient-matched diagnosis and relapse (PAML) specimens (study cohort). A set of five differentially expressed genes (DEGs; STAT4, XRCC2, USP3, CEBPD, RBM47) with concordant changes in expression between diagnosis and relapse (Figure 1A) were selected for study using the following criteria: (a) concordant differential expression (DESeq2: log2FC > |1.2| and q < 0.05) in at least 25% of the relapsed patients in the study cohort (b) concordant differential expression in independent datasets of RNA-Seq without any experimental validation, and (c) high cancer driver potential based on their molecular function. Binding analysis for regulation of transcription (BART) on DEGs between normal CD34 + cells, diagnosis and relapsed AML patient specimens suggested that CEBPD could function as a transcriptional regulator of a subset of the DEGs. We hypothesized that dysregulated expression of these genes promotes AML disease progression.
To examine their role in AML, we altered their expression in AML cell line models and measured changes in AML cell phenotypes. Of these genes, CRISPR-mediated knockdown of the transcription factor CCAAT/enhancer-binding protein delta (CEBPD) enhanced AML cell proliferation, self-renewal capacity, and survival of the relapsed AML cell line OCI-AML5. CEBPD knockdown also conferred OCI-AML5 resistance to cytarabine - a common chemotherapy drug used for AML treatment. Short hairpin RNA (shRNA)-mediated knockdown of CEBPD in OCI-AML5 validated these results. CRISPR-mediated upregulation of CEBPD expression induced monocyte/macrophage differentiation marker CD14 expression and enhanced apoptosis rates in OCI-AML5 cells. CEBPD upregulation also induced differentiation in the diagnosis AML cell line OCI-AML2. Survival analyses showed that lower expression of CEBPD was significantly associated with poor survival in pediatric AML patients, and there was a trend of lower CEBPD expression associating with worse survival in adult AML patients (UCSC Xena browser). These results altogether suggest that CEBPD plays a tumor suppressor role in AML. Gene set enrichment analyses (GSEA) on RNA-Seq data revealed significant positive enrichment of cell proliferation pathways upon CEBPD knockdown in OCI-AML5 cells as well as in a subset of the PAML patients with downregulated CEBPD expression at relapse. Differential gene expression and GSEA analyses altogether suggested upregulated cyclin D1 as one of the downstream drivers of enhanced growth of AML cells with repressed CEBPD expression (Figure 1B). RT-qPCR and Western Blot experiments confirmed upregulation of CCND1 expression in CEBPD knockdown OCI-AML5 and OCI-AML2 cells. Next, we sought to understand the molecular mechanisms repressing CEBPD expression during AML disease progression. We found an inverse association between CEBPD and DNMT3 methyltransferases mRNA expression in PAML and independent datasets. Treatment with the hypomethylating agent azacitidine upregulated CEBPD mRNA expression in multiple AML cell lines including OCI-AML5 and OCI-AML2, suggesting that hypermethylation represses CEBPD gene expression in these AML cells. Integrative analysis of gene expression with DNA methylation at the CEBPD promoter identified hypermethylation of multiple CpGs within the binding region of the transcription factor Sp1 in a subset of patients with CEBPD downregulation. CpG methylation has been shown to interfere with Sp1 binding at the CEBPD promoter. Since Sp1 binding promotes CEBPD transcription, hypermethylation at these sites may repress CEBPD expression during AML disease progression.
Our study suggests that CEBPD can function as tumor suppressor in AML. Results suggest a role for DNA methylation in repressing CEBPD expression during AML disease progression. Furthermore, we show that CEBPD repression promotes AML cells' growth potentially via inducing the expression of the cell cycle driver CCND1.
Background: Acute myeloid leukemia in patients over the age of 60 (aAML) is associated with poor prognosis. aAML patients are the majority diagnosed but are underrepresented in large molecular ...studies. We have identified two clinical subgroups of aAML patients with distinct survival outcomes (low-risk and high-risk) in ECOG-ACRIN Cancer Research Group's clinical trial E3999 (NCT00046930). We hypothesize that these two groups are characterized by distinct biological mechanisms that contribute to leukemogenesis. We also hypothesize that the low-risk group harbor molecular and phenotypic signatures characteristic of known better-risk AMLs.
Methods: Diagnostic specimens were obtained from patients enrolled in NCT00046930. Disease enriched cells were isolated by negative selection of lymphocytes (magnetic beads). Flow cytometry was used to characterize the blast population. Bulk RNA-sequencing was performed on 220 blast enriched samples and 10 age matched normal controls (CD34+ bone marrow cells). Transcriptional differences were determined using DESeq2. Differentially expressed genes (DEGs) were identified as those with an absolute log2 fold change greater than 1 and q less than 0.05. Gene set enrichment analysis (GSEA) was performed against the MSigDB databases. Upstream regulators associated with gene expression changes were identified using Ingenuity Pathway Analysis (IPA). DESeq2 was used to identify genes that were differentially associated with overall survival times between the risk groups. Enrichment for transcription factor gene targets was calculated using EnrichR based on the CHEA Transcription Factor Target Dataset. Cytokines were quantified in a subset of patient serum samples using a Luminex assay.
Results: We identified 2314 DEGs between the low-risk and high-risk aAMLs with high-risk as the baseline. The upregulated genes in the low-risk aAMLs were positively enriched for gene signatures derived from: 1. Favorable risk AML ( NPM1 mutated), 2. M4 and M5 AML patients, 3. Differentiated hematopoietic cells and 4. Inflammatory response pathways. On the contrary, upregulated genes in the high-risk aAMLs were enriched for gene signatures identified in hematopoietic and leukemic stem cells and known poor-risk AMLs (for example: EVI1 fusion). Accordingly, immunophenotypic data from flow cytometry results gated on the blast populations validated differences in the surface expression of hematopoietic cell markers between the two groups. Next, we sought to determine upstream regulators associated with the DEGs using IPA. We identified 107 potential upstream regulators that associated with the changes in gene expression observed between the low- and high-risk groups (87 activated and 20 inhibited). The results suggested that several pro-inflammatory cytokines (ex. tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ)) were predicted activators in the low-risk aAML group. Accordingly, we detected significantly higher levels of TNFα and IFNγ in the serum levels of a subset of low-risk aAML patients. Finally, we assessed for genes whose expression significantly associated with overall survival. Interestingly, in agreement with a previously proposed inflammation score (iScore), we identified higher iScore associated with the high-risk group. Of note, the upstream regulators identified do not overlap with those contributing to the calculation of iScore. Additionally, longer overall survival times were associated with higher levels of expression of genes associated with heme metabolism and erythroblast differentiation in the low-risk aAML patient group.
Conclusions: Our results suggest that the low-risk aAML patients were characterized by a more mature hematopoietic cell gene expression signature and cell surface markers as well as a pro-inflammatory state. Our study supports the possibility that pro-inflammatory cytokines and/or signaling could mediate AML cell survival in the low-risk aAML patient group. The high-risk aAML patients were characterized by a more primitive hematopoietic and leukemic stem cell gene expression signature. Collectively, we propose that differences in the underlying molecular and/or immune-based mechanisms could contribute to leukemogenesis in the two risk groups. These findings suggest that distinct therapeutic approaches may need to be considered to improve clinical outcomes in the two aAML risk groups.
Metal–organic frameworks (MOFs) have been evaluated as potential nanocarriers for intraocular incorporation of brimonidine tartrate to treat chronic glaucoma. Experimental results show that UiO-67 ...and MIL-100 (Fe) exhibit the highest loading capacity with values up to 50–60 wt %, whereas the performance is quite limited for MOFs with narrow cavities (below 0.8 nm, for example, UiO-66 and HKUST-1). The large loading capacity in UiO-67 is accompanied by an irreversible structural amorphization in aqueous and physiological media that promotes extended release kinetics above 12 days. Compared to the traditional drawbacks associated with the sudden release of the commercial drugs (e.g., ALPHAGAN), these results anticipate UiO-67 as a potential nanocarrier for drug delivery in intraocular therapeutics. These promising results are further supported by cytotoxicity tests using retinal photoreceptor cells (661W). Toxicity of these structures (including the metal nodes and organic ligands) for retinal cells is rather low for all samples evaluated, except for HKUST-1.
•First comprehensive identification of walnuts polyphenols by LTQ-Orbitrap.•Eight polyphenols identified for the first time in walnuts.•Ellagitannins, ellagic acid and its derivatives, were the major ...polyphenols of walnuts.•MS/MS fragmentation of flavano-ellagitannin hybrids is for the first time reported.
Epidemiologic studies and clinical trials have demonstrated consistent benefits of walnut consumption on coronary heart disease risk and other chronic diseases. Walnuts (Juglans regia L.) have been described previously as a rich source of polyphenols with a broad array of different structures. However, an accurate screening of its complete phenolic profile is still lacking. In the present work, liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole-Orbitrap mass spectrometry (LC–LTQ-Orbitrap) was applied for a comprehensive identification of phenolic compounds in walnuts. A total of 120 compounds, including hydrolysable and condensed tannins, flavonoids and phenolic acids were identified or tentatively identified on the base of their retention times, accurate mass measurements and subsequent mass fragmentation data, or by comparing with reference substances and literature. The peak area of each signal in mass chromatograms was used to provide semiquantitative information for comparison purposes. The most abundant ions were observed for ellagitannins, ellagic acid and its derivatives. Furthermore, the high-resolution MS analysis revealed the presence of eight polyphenols that have never been reported in walnuts: stenophyllanin C, malabathrin A, eucalbanin A, cornusiin B, heterophylliin E, pterocarinin B, reginin A and alienanin B.
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