Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes.

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. ), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality.

Lipid desaturation regulates the balance between self-renewal and differentiation in mouse blastocyst-derived stem cells.

Stem cells are defined by their ability to self-renew and differentiate, both shown in multiple studies to be regulated by metabolic processes. To decipher metabolic signatures of self-renewal in blastocyst-derived stem cells, we compared early differentiating embryonic stem cells (ESCs) and their extra-embryonic counterparts, trophoblast (T)SCs to their self-renewing counterparts. A metabolomics analysis pointed to the desaturation of fatty acyl chains as a metabolic signature of differentiating blastocyst-derived SCs via the upregulation of delta-6 desaturase (D6D; FADS2) and delta-5 desaturase (D5D; FADS1), key enzymes in the biosynthesis of polyunsaturated fatty acids (PUFAs).

Glutamate catabolism during sporulation determines the success of the future spore germination.

Bacterial spores can preserve cellular dormancy for years, but still hold the remarkable ability to revive and recommence life. This cellular awakening begins with a rapid and irreversible event termed germination; however, the metabolic determinants required for its success have been hardly explored. Here, we show that at the onset of the process of sporulation, the metabolic enzyme RocG catabolizes glutamate, facilitating ATP production in the spore progenitor cell, and subsequently influencing the eventual spore ATP reservoir.

Activation of the Type III Secretion System of Enteropathogenic Escherichia coli Leads to Remodeling of Its Membrane Composition and Function.

The cell envelope of Gram-negative bacteria is a complex structure, essential for bacterial survival and for resistance to many antibiotics. Channels that cross the bacterial envelope and the host cell membrane form secretion systems that are activated upon attachment to host, enabling bacteria to inject effector molecules into the host cell, required for bacterium-host interaction. The type III secretion system (T3SS) is critical for the virulence of several pathogenic bacteria, including enteropathogenic Escherichia coli (EPEC).

Distinct infrastructure of lipid networks in visceral and subcutaneous adipose tissues in overweight humans.

Background: Adipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue-specific roles in systemic metabolic perturbations.

Objective: We sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications.

A Shift in Glycerolipid Metabolism Defines the Follicular Fluid of IVF Patients with Unexplained Infertility.

Follicular fluid (FF) constitutes the microenvironment of the developing oocyte. We recently characterized its lipid composition and found lipid signatures of positive pregnancy outcome after in vitro fertilization (IVF). In the current study, we aimed to test the hypothesis that unexplained female infertility is related to lipid metabolism, given the lipid signature of positive-outcome IVF patients we previously found.

Multi-platform NMR Study of Pluripotent Stem Cells Unveils Complementary Metabolic Signatures towards Differentiation.

Stem cells, poised to revolutionize current medicine, stand as major workhorses for monitoring changes in cell fate. Characterizing metabolic phenotypes is key to monitor in differentiating cells transcriptional and epigenetic shifts at a functional level and provides a non-genetic means to control cell specification. Expanding the arsenal of analytical tools for metabolic profiling of cell differentiation is therefore of importance.

A shift in follicular fluid from triacylglycerols to membrane lipids is associated with positive pregnancy outcome.

Follicular fluid (FF) is a liquid that surrounds the ovum. Its metabolite and, specifically, its lipid content have been associated with oocyte development. To characterize possible association between the lipid composition of FF and the outcome of pregnancy, we carried out a lipidomics study and compared the abundance of lipids from FF of patients with positive and negative outcomes.

The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing.

Nutrient sensing pathways adjust metabolism and physiological functions in response to food intake. For example, sugar feeding promotes lipogenesis by activating glycolytic and lipogenic genes through the Mondo/ChREBP-Mlx transcription factor complex. Concomitantly, other metabolic routes are inhibited, but the mechanisms of transcriptional repression upon sugar sensing have remained elusive.

Concise Review: Energy Metabolites: Key Mediators of the Epigenetic State of Pluripotency.

Recent studies suggest that the metabolic network is an important part of the molecular circuitry that underlies pluripotency. Of the metabolic pathways that were implicated in the pluripotency balance, "energy" metabolism is particularly notable. Its mechanism of action on pluripotency-regulating genes has been partially elucidated when three metabolites, namely acetate, S-adenosylmethionine, and O-linked β-N-acetylglucosamine were recently shown to link cytosolic signals to pluripotent gene expression.

Microbial-derived lithocholic acid and vitamin K2 drive the metabolic maturation of pluripotent stem cells-derived and fetal hepatocytes.

Unlabelled: The liver is the main organ responsible for the modification, clearance, and transformational toxicity of most xenobiotics owing to its abundance in cytochrome P450 (CYP450) enzymes. However, the scarcity and variability of primary hepatocytes currently limits their utility. Human pluripotent stem cells (hPSCs) represent an excellent source of differentiated hepatocytes; however, current protocols still produce fetal-like hepatocytes with limited mature function.

Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells.

Loss of pluripotency is a gradual event whose initiating factors are largely unknown. Here we report the earliest metabolic changes induced during the first hours of differentiation. High-resolution NMR identified 44 metabolites and a distinct metabolic transition occurring during early differentiation.

High-resolution metabolic mapping of cell types in plant roots.

Metabolite composition offers a powerful tool for understanding gene function and regulatory processes. However, metabolomics studies on multicellular organisms have thus far been performed primarily on whole organisms, organs, or cell lines, losing information about individual cell types within a tissue. With the goal of profiling metabolite content in different cell populations within an organ, we used FACS to dissect GFP-marked cells from Arabidopsis roots for metabolomics analysis.

Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals.

Incensole acetate (IA), a constituent of Boswellia resin ('frankincense'), was previously demonstrated to exhibit an antidepressive-like effect in the Forced Swim Test (FST) in mice following single dose administration (50 mg/kg). Here, we show that acute administration of considerably lower dose (10 mg/kg) IA to selectively bred mice, showing prominent submissive behavior, exerted significant antidepressant-like effects in the FST. Furthermore, chronic administration of 1 or 5 mg/kg per day of IA for three consecutive weeks dose- and time-dependently reduced the submissiveness of the mice in the Dominant-Submissive Relationship test, developed to screen the chronic effect of antidepressants.

Cell type-specific transcriptional profiling: implications for metabolite profiling.

Plant development and survival is centered on complex regulatory networks composed of genes, proteins, hormone pathways, metabolites and signaling pathways. The recent advancements in whole genome biology have furthered our understanding of the interactions between these networks. As a result, numerous cell type-specific transcriptome profiles have been generated that have elucidated complex gene regulatory networks occurring at the cellular level, many of which were masked during whole-organ analysis.

Protective effects of incensole acetate on cerebral ischemic injury.

The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage.

Evaluation of peak picking quality in LC-MS metabolomics data.

The output of LC-MS metabolomics experiments consists of mass-peak intensities identified through a peak-picking/alignment procedure. Besides imperfections in biological samples and instrumentation, data accuracy is highly dependent on the applied algorithms and their parameters. Consequently, quality control (QC) is essential for further data analysis.

Boswellia resin: from religious ceremonies to medical uses; a review of in-vitro, in-vivo and clinical trials.

Objectives: Despite its historical-religious, cultural and medical importance, Boswellia has not been thoroughly studied, and gaps still exist between our knowledge of the traditional uses of the resin and the scientific data available. Here we review the pharmacology of Boswellia resin and of the small molecules identified as the active ingredients of the resin.

Key Findings: The resin of Boswellia species ('frankincense', 'olibanum') has been used as incense in religious and cultural ceremonies since the beginning of written history.

Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain.

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown.

Incensole acetate: a novel neuroprotective agent isolated from Boswellia carterii.

Boswellia resin has been used as a major anti-inflammatory agent and for the healing of wounds for centuries. Incensole acetate (IA), isolated from this resin, was shown to inhibit the activation of nuclear factor-kappaB, a key transcription factor in the inflammatory response. We now show that IA inhibits the production of inflammatory mediators in an in vitro model system of C6 glioma and human peripheral monocytes.

Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells for a bioassay-guided fractionation.

Myrrh--Commiphora chemistry.

Myrrh and opopanax has been used throughout history in incense and as a perfume. Since Bible times it has been used for the treatment of wounds. The first attempts to identify content compounds were almost 100 years ago.

The Jerusalem Balsam: from the Franciscan Monastery in the old city of Jerusalem to Martindale 33.

The Jerusalem Balsam, a remedy based on an ethanolic extract of a herbal mixture, was formulated in 1719 in the pharmacy of the Saint Savior monastery in the old city of Jerusalem. Having gained fame, the Jerusalem Balsam was replicated and prepared in Europe. One can still find variations of the formula in current pharmacopoeias (B.

Synthesis and evaluation of oxazaborolidines for antibacterial activity against Streptococcus mutans.

Several representative oxazaborolidines have been synthesized and evaluated against S. mutans for antibacterial activity. This is the first reported antibacterial activity of this class of compounds.