The relationship between dietary sulfur amino acids intake and severity and frequency of pain in Iranian patients with musculoskeletal pains, 2020

Objective Musculoskeletal pain conditions (MPs) are a widespread public problem that can affect 13.5% to 47% of the total population. Dietary changes can have strong effects on person’s health; for instance, Sulfur amino acids (SAAs) can act as a precursor of neurotransmitters, antioxidative metabolic intermediates, such as glutathione, impact inflammation, and play a role in severity and frequency of MPs. We evaluated the relationship between dietary SAAs intake with severity and frequency of pain in patients with MPs. Results This cross-sectional study consisted of 175 men and woman. Anthropometric measurements and pain assessments were conducted via questionnaires. Dietary data were collected using 7 days 24-h recall. ANOVA and Spearman correlation coefficients were used to examine the relationship and correlation, respectively, between exposure and outcome variables. There was a significant correlation between age, weight, waist circumference (WC), waist circumference to height (WHtR), body mass index (BMI), and severity and frequency of MPs among women. There was a correlation between age and severity of pain in men. The present study highlights a positive association between the dietary SAAs and severity of pain, even after adjusting for confounding variables.

Purine Auxotrophic Starvation Evokes Phenotype Similar to Stationary Phase Cells in Budding Yeast

Purine auxotrophy is an abundant trait among eukaryotic parasites and a typical marker for many budding yeast strains. Supplementation with an additional purine source (such as adenine) is necessary to cultivate these strains. If not supplied in adequate amounts, purine starvation sets in. We explored purine starvation effects in a model organism, a budding yeast Saccharomyces cerevisiae ade8 knockout, at the level of cellular morphology, central carbon metabolism, and global transcriptome. We observed that purine-starved cells stopped their cycle in G1/G0 state and accumulated trehalose, and the intracellular concentration of AXP decreased, but adenylate charge remained stable. Cells became tolerant to severe environmental stresses. Intracellular RNA concentration decreased, and massive downregulation of ribosomal biosynthesis genes occurred. We proved that the expression of new proteins during purine starvation is critical for cells to attain stress tolerance phenotype Msn2/4p targets are upregulated in purine-starved cells when compared to cells cultivated in purine-rich media. The overall transcriptomic response to purine starvation resembles that of stationary phase cells. Our results demonstrate that the induction of a strong stress resistance phenotype in budding yeast can be caused not only by natural starvation, but also starvation for metabolic intermediates, such as purines.

Bioconversion of Lignocellulosic Biomass into Value Added Products under Anaerobic Conditions: Insight into Proteomic Studies

Production of biofuels and other value-added products from lignocellulose breakdown requires the coordinated metabolic activity of varied microorganisms. The increasing global demand for biofuels encourages the development and optimization of production strategies. Optimization in turn requires a thorough understanding of the microbial mechanisms and metabolic pathways behind the formation of each product of interest. Hydrolysis of lignocellulosic biomass is a bottleneck in its industrial use and often affects yield efficiency. The accessibility of the biomass to the microorganisms is the key to the release of sugars that are then taken up as substrates and subsequently transformed into the desired products. While the effects of different metabolic intermediates in the overall production of biofuel and other relevant products have been studied, the role of proteins and their activity under anaerobic conditions has not been widely explored. Shifts in enzyme production may inform the state of the microorganisms involved; thus, acquiring insights into the protein production and enzyme activity could be an effective resource to optimize production strategies. The application of proteomic analysis is currently a promising strategy in this area. This review deals on the aspects of enzymes and proteomics of bioprocesses of biofuels production using lignocellulosic biomass as substrate.

The existence of a nonclassical TCA cycle in the nucleus that wires the metabolic-epigenetic circuitry

The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.

Organ-specific, integrated omics data-based study on the metabolic pathways of the medicinal plant Bletilla striata (Orchidaceae)

Background Bletilla striata is one of the important species belonging to the Bletilla genus of Orchidaceae. Since its extracts have an astringent effect on human tissues, B. striata is widely used for hemostasis and healing. Recently, some other beneficial effects have also been uncovered, such as antioxidation, antiinflammation, antifibrotic, and immunomodulatory activities. As a key step towards a thorough understanding on the medicinal ingredient production in B. striata, deciphering the regulatory codes of the metabolic pathways becomes a major task. Results In this study, three organs (roots, tubers and leaves) of B. striata were analyzed by integrating transcriptome sequencing and untargeted metabolic profiling data. Five different metabolic pathways, involved in polysaccharide, sterol, flavonoid, terpenoid and alkaloid biosynthesis, were investigated respectively. For each pathway, the expression patterns of the enzyme-coding genes and the accumulation levels of the metabolic intermediates were presented in an organ-specific way. Furthermore, the relationships between enzyme activities and the levels of the related metabolites were partially inferred. Within the biosynthetic pathways of polysaccharides and flavonoids, long-range phytochemical transportation was proposed for certain metabolic intermediates and/or the enzymes. Conclusions The data presented by this work could strengthen the molecular basis for further studies on breeding and medicinal uses of B. striata.

ICA treatment diabets induced bone loss via primary cilia/Gli2/Osteocalcin signaling pathway

Diabetes mellitus, as a metabolic system disorder disease, aggravates the disease burden of patients and affects the quality of human life. Diabetes-associatedbone complications lead to decreased bone mechanical strength and osteoporosis.Evidencesshow that chronic hyperglycemia and metabolic intermediates , such as inflammatory factor, reactive oxygen species(ROS) and advanced glycation end products(AGEs), are regarded as dominanthazardous factors of primary cilia/Gli2 signal disorders.Case studies have demonstrated abnormal bone metabolism in diabetics, however, how diabetes damages primarycilia/Gli2 signal is largely unknown. Therefore, we studied the effects of diabetes on femoral primary cilia by establishing aStreptozocin (STZ)-induced diabetic (SpragueDawley) SD rat model and diabetic bone loss cell modelin vitro. Our results confirmed that diabetes impaired femur primary cilia,osteoblast differentiation and mineralization by inhibiting primary cilia/Gli2signaling pathway, additionally,Icariin(ICA) treatment could rescue the impairment of osteoblast differentiation causedby high glucose mediumin vitro. ICA activated primary cilia/Gli2/osteocalcinsignaling pathway of osteoblasts by protecting primary cilia from glucotoxicityimposed by diabetes, intactprimary cilia couldbe as anchoring sites, in which Gli2 was processed and modified,and matured Gli2 entered the nucleus to initiate downstream osteocalcingene transcription.Additionally,ICA inhibited ROS production of mitochondria, thus balanced mitochondrial energy metabolism and oxidative phosphorylation.All results suggest that ICA can protect the primary cilia and mitochondria of osteoblastby reducingintracellular ROS, thereby recover primary cilia/Gli2signaling pathway to facilitateosteoblast differentiation and mineralization, suggesting that ICA has potential as a novel typeof drugtreatingbone loss induced bydiabetes.

High Temperature Increased Lignin Contents of Poplar (Populus spp) Stem via Inducing the Synthesis Caffeate and Coniferaldehyde

Background Lignin contributes to plant resistance to biotic and abiotic stresses and is dominantly regulated by enzymes which catalyze the generation of metabolites intermediates in lignin synthesis. However, the response of lignin and its key regulatory factors to high temperature stress are poorly unknown. Results Here, this finding revealed that the content of lignin in poplar (Populus spp) stem increased after three days of high temperature stress treatment. In fourteen metabolic intermediates of lignin biosynthetic pathway with targeted metabolomics analysis, caffeate and coniferaldehyde increased evidently upon heat stress. C3’H (p-Coumaroylshikimate 3-hydroxylase) and CCR (Cinnamoyl-CoA reductase) are recognized to catalyze the formation of caffeate and coniferaldehyde, respectively. Transcriptome data and RT-qPCR (reverse transcription-quantitative real-time polymerase chain reaction) analysis found the high transcriptional level of PtrMYBs (PtrMYB021, PtrMYB074, PtrMYB85, PtrMYB46), PtrC3’H1 (Potri.006G033300) and PtrCCR2 (Potri.003G181400), suggesting that they played the vital role in the increase of lignin and its metabolic intermediates induced by high temperature. Conclusions The discovery of key regulators and metabolic intermediates in lignin pathway that respond to high temperature provides a theoretical basis for quality improvement of lignin and the application of forest resources.

Nicotinate degradation in a microbial eukaryote: a novel, complete pathway extant in Aspergillus nidulans

Several strikingly different aerobic and anaerobic pathways of nicotinate utilization had been described in bacteria. No similar work is extant in any eukaryote. Here we elucidate a complete eukaryotic nicotinate utilization pathway, by constructing single or multiple gene deleted strains and identifying metabolic intermediates by ultra-high performance liquid chromatography — high-resolution mass spectrometry. Enzymes catalyzing each step and all intermediate metabolites were identified. We previously established that the cognate eleven genes organized in three clusters constitute a regulon, strictly dependent on HxnR, a pathway-specific transcription factor. The first step, hydroxylation of nicotinic acid to 6-hydroxynicotinic acid is analogous to that occurring in bacterial pathways and is catalyzed by an independently evolved molybdenum-containing hydroxylase. The following enzymatic steps have no prokaryotic equivalents: 6-hydroxynicotinic acid is converted to 2,3,6-trihydroxypyridine through 2,5-dihydroxypiridine and the trihydroxylated pyridine ring is then saturated to 5,6-dihydroxypiperidine-2-one followed by the oxidation of the C6 hydroxyl group resulting in 3-hydroxypiperidine-2,6-dione. The latter two heterocyclic compounds are newly identified cellular metabolites, while 5,6-dihydroxypiperidine-2-one is a completely new chemical compound. Ring opening between C and N results in α-hydroxyglutaramate, an unprecedented compound in prokaryotic nicotinate catabolic routes. The pathway extant in A. nidulans, and in many other ascomycetes, is different from any other previously analyzed in bacteria. Our earlier phylogenetic analysis of Hxn proteins together with the complete novel biochemical pathway we now describe further illustrates the convergent evolution of catabolic pathways between fungi and bacteria.

Degradation of Bile Acids by Soil and Water Bacteria

Bile acids are surface-active steroid compounds with a C5 carboxylic side chain at the steroid nucleus. They are produced by vertebrates, mainly functioning as emulsifiers for lipophilic nutrients, as signaling compounds, and as an antimicrobial barrier in the duodenum. Upon excretion into soil and water, bile acids serve as carbon- and energy-rich growth substrates for diverse heterotrophic bacteria. Metabolic pathways for the degradation of bile acids are predominantly studied in individual strains of the genera Pseudomonas, Comamonas, Sphingobium, Azoarcus, and Rhodococcus. Bile acid degradation is initiated by oxidative reactions of the steroid skeleton at ring A and degradation of the carboxylic side chain before the steroid nucleus is broken down into central metabolic intermediates for biomass and energy production. This review summarizes the current biochemical and genetic knowledge on aerobic and anaerobic degradation of bile acids by soil and water bacteria. In addition, ecological and applied aspects are addressed, including resistance mechanisms against the toxic effects of bile acids.