Metabolic and Physiological Regulation of Aspartic Acid-Mediated Enhancement of Heat Stress Tolerance in Perennial Ryegrass

Aspartate is the most critical amino acid in the aspartate metabolic pathway, which is associated with multiple metabolic pathways, such as protein synthesis, nucleotide metabolism, TCA cycle, glycolysis, and hormone biosynthesis. Aspartate also plays an important role in plant resistance to abiotic stress, such as cold stress, drought stress, salt stress or heavy metal stress. This study found that the chlorophyll content and antioxidant active enzyme content (SOD, CAT, POD and APX) of perennial ryegrass treated with 2 mM aspartate were significantly higher than those treated with water under heat stress. The electrolyte leakage rate, MDA content and peroxide levels (O2− and H2O2) of perennial ryegrass treated with aspartate were significantly lower than those of perennial ryegrass treated with water, indicating that exogenous aspartate increases the content of chlorophyll, maintain the integrity of cell membrane system, and enhances SOD-CAT antioxidant pathway to eliminate the oxidative damage caused by ROS in perennial ryegrass under heat stress. Furthermore, exogenous aspartate could enhance the TCA cycle, the metabolism of the amino acids related to the TCA cycle, and pyrimidine metabolism to enhance the heat tolerance of perennial ryegrass.

Sea Anemones Responding to Sex Hormones, Oxybenzone, and Benzyl Butyl Phthalate: Transcriptional Profiling and in Silico Modelling Provide Clues to Decipher Endocrine Disruption in Cnidarians

Endocrine disruption is suspected in cnidarians, but questions remain how occurs. Steroid sex hormones are detected in corals and sea anemones even though these animals do not have estrogen receptors and their repertoire of steroidogenic enzymes appears to be incomplete. Pathways associated with sex hormone biosynthesis and sterol signaling are an understudied area in cnidarian biology. The objective of this study was to identify a suite of genes that can be linked to exposure of endocrine disruptors. Exaiptasia diaphana were exposed to nominal 20ppb concentrations of estradiol (E2), testosterone (T), cholesterol, oxybenzone (BP-3), or benzyl butyl phthalate (BBP) for 4 h. Eleven genes of interest (GOIs) were chosen from a previously generated EST library. The GOIs are 17β-hydroxysteroid dehydrogenases type 14 (17β HSD14) and type 12 (17β HSD12), Niemann-Pick C type 2 (NPC2), Equistatin (EI), Complement component C3 (C3), Cathepsin L (CTSL), Patched domain-containing protein 3 (PTCH3), Smoothened (SMO), Desert Hedgehog (DHH), Zinc finger protein GLI2 (GLI2), and Vitellogenin (VTG). These GOIs were selected because of functional associations with steroid hormone biosynthesis; cholesterol binding/transport; immunity; phagocytosis; or Hedgehog signaling. Quantitative Real-Time PCR quantified expression of GOIs. In silico modelling utilized protein structures from Protein Data Bank as well as creating protein structures with SWISS-MODEL. Results show transcription of steroidogenic enzymes, and cholesterol binding/transport proteins have similar transcription profiles for E2, T, and cholesterol treatments, but different profiles when BP-3 or BBP is present. C3 expression can differentiate between exposures to BP-3 versus BBP as well as exposure to cholesterol versus sex hormones. In silico modelling revealed all ligands (E2, T, cholesterol, BBP, and BP-3) have favorable binding affinities with 17β HSD14, 17β HSD12, NPC2, SMO, and PTCH proteins. VTG expression was down-regulated in the sterol treatments but up-regulated in BP-3 and BBP treatments. In summary, these eleven GOIs collectively generate unique transcriptional profiles capable of discriminating between the five chemical exposures used in this investigation. This suite of GOIs are candidate biomarkers for detecting transcriptional changes in steroidogenesis, gametogenesis, sterol transport, and Hedgehog signaling. Detection of disruptions in these pathways offers new insight into endocrine disruption in cnidarians.

FBLN5 Is an Underlying Common Tumor Suppressor in Breast Cancer and Thyroid Cancer

Background: Breast cancer (BC) patients have a greater risk of developing thyroid cancer (TC) than the general population. Similarly, TC patients are more likely to develop BC, suggesting an underlying common etiology. In this study, we sought to identify the potential cross-talking pathway and related molecular mechanisms conferring to the sequential development of BC and TC.Methods: We first used Multiple Primary-Standardized Incidence Ratios (MP-SIR) Program of SEER*Stat to calculate SIR to confirm the relationship between BC and TC. Then the RNA-seq was downloaded from The Cancer Genome Atlas (TCGA). And we built a co-expression network via Weighted Gene Co-expression Network Analysis (WGCNA) and obtained the most significant modules. The key genes were obtained by differential gene expression (DGE) analysis and WGCNA analysis. Furthermore, String database and Cytoscape software were used to construct protein-protein interactions (PPI), and defined the maximum Maximal Clique Centrality (MCC) value as hub gene.Then we performed prognosis analysis on the hub genes and obtained the prognostic genes of BC and TC. Finally, gene set enrichment analysis (GSEA) was used to investigate the molecular pathways associated with prognostic gene expressed both in BC and TC.Results: From the SEER database, we found that the risk of developing BC in TC patients was SIR 1.12, 95% CI [1.07, 1.18], and the risk of developing BC in TC patients was SIR 1.29, 95% CI [1.23, 1.26]. Fifty-nine key genes obtained by differential expression analysis and WGCNA identify that PI3K/AKT was the most enriched pathway in BC and TC. In addition, the Recombinant Fibulin 5 (FBLN5) was shown to be of significant prognostic value for both BC and TC and was down-regulated in BC and TC tissues. GSEA demonstrated that FBLN5 enrichment pathways associated with BC and TC mainly included: B cell receptor signaling pathway, steroid hormone biosynthesis, and pathways in cancer.Conclusions: The PI3K/AKT signaling is most co-enriched pathway in BC and TC. FBLN5 is the most relevant prognostic gene and an underlying common tumor suppressor in both BC and TC, with down-stream pathways involving immunity, hormone biosynthesis and carcinogenesis.

Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis

Background: Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with ZSYT pills. However, the pharmacological mechanism of action of these pills remains unclear.Methods: The components of ZSYT found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of ZSYT pills. The potential targets of components were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and SwissTargetPrediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, therapeutic target database, and Genetic Association Database. The overlapping genes between the potential targets of ZSYT components and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis.Results: Nineteen components in ZSYT pills were detected in the serum of POF mice after oral administration. A total of 695 ZSYT-related targets was screened, and 344 POF-related targets were collected. From the results of ZSYT-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with ZSYT pills. Moreover, the pathway enrichment results suggested that ZSYT pills treat POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis.Conclusions: We demonstrated that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis are very likely to be therapeutic mechanism of ZSYT pills in treating POF. Our study suggests that combining the analysis of ZSYT pills components in blood in vivo in the POF models and network pharmacology prediction may offer a tool to characterize the mechanism of ZSYT pills in the POF.

Transcriptomic Analysis of the Pistacia vera (L.) Fruits Enable the Identification of Genes and Hormone-Related Gene Linked to Inflorescence Bud Abscission

Pistacia vera (L.) is an alternate bearing species. The tree produces axillary inflorescence buds every year. Still, they abscise in “ON” overloaded shoots, causing a limited production in the following “OFF” year, causing a significant and unfavorable production fluctuation. In this work, we carried out de novo discovery and transcriptomic analysis in fruits of “ON” and “OFF” shoots of the cultivar Bianca. We also investigated whether the fruit signaling pathway and hormone biosynthesis directly or indirectly linked to the premature fall of the inflorescence buds causing alternate bearing. We identified 1536 differentially expressed genes (DEGs) in fruits of “ON” vs. “OFF” shoots, which are involved primarily in sugar metabolism, plant hormone pathways and transcription factors. The premature bud abscission linked to the phenomenon is attributable to a lack of nutrients (primarily sugar) and the possible competition between the same branches’ sinks (fruits vs. inflorescence buds). Hormone pathways are involved as a response to signals degradation and remobilization of carbon and nutrients due to the strengthening of the developing embryos. Genes of the secondary metabolism and transcription factors are also involved in tailoring the individual branches response to the nutritional stress and sink competition. Crosstalk among sugar and various hormone-related genes, e.g., ethylene, auxin, ABA and cytokinin, were determined. The discovery of putative biomarkers like callose synthase 5, trehalose-6-phosphate synthase, NAD(P)-linked oxidoreductase and MIOX2, Jasmonate, and salicylic acid-related genes can help to design precision farming practices to mitigate the alternate bearing phenomenon to increase farming profitability. The aim of the analysis is to provide insight into the gene expression profiling of the fate of “ON” and “OFF” fruits associated with the alternate bearing in the pistachio.

Phenylacetylglutamine, a Novel Biomarker in Acute Ischemic Stroke

Background: To discover novel metabolic biomarkers of ischemic stroke (IS), we carried out a two-stage metabolomic profiling of IS patients and healthy controls using untargeted and targeted metabolomic approaches.Methods: We applied untargeted liquid chromatography-mass spectrometry (LC-MS) to detect the plasma metabolomic profiles of 150 acute IS patients and 50 healthy controls. The candidate differential microbiota-derived metabolite phenylacetylglutamine (PAGln) was validated in 751 patients with IS and 200 healthy controls. We evaluated the associations between PAGln levels and the severity and functional outcomes of patients with IS. Clinical mild stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score 0–5, and moderate-severe stroke as NIHSS score >5. A favorable outcome at 3 months after IS was defined as the modified Rankin Scale (mRS) score 0–2, and unfavorable outcome as mRS score 3–6.Results: In untargeted metabolomic analysis, we detected 120 differential metabolites between patients with IS and healthy controls. Significantly altered metabolic pathways were purine metabolism, TCA cycle, steroid hormone biosynthesis, and pantothenate and CoA biosynthesis. Elevated plasma PAGln levels in IS patients, compared with healthy controls, were observed in untargeted LC-MS analysis and confirmed by targeted quantification (median 2.0 vs. 1.0 μmol/L; p < 0.001). Patients with moderate-severe stroke symptoms and unfavorable short-term outcomes also had higher levels of PAGln both in discovery and validation stage. After adjusting for potential confounders, high PAGln levels were independently associated with IS (OR = 3.183, 95% CI 1.671–6.066 for the middle tertile and OR = 9.362, 95% CI 3.797–23.083 for the highest tertile, compared with the lowest tertile) and the risk of unfavorable short-term outcomes (OR = 2.286, 95% CI 1.188–4.401 for the highest tertile).Conclusions: IS patients had higher plasma levels of PAGln than healthy controls. PAGln might be a potential biomarker for IS and unfavorable functional outcomes in patients with IS.

Integrated multiple transcriptomes in oviductal tissue across the porcine oestrous cycle reveal functional roles in oocyte maturation and transport

Understanding the changes in the swine female reproductive system is important for solving issues related to reproductive failure and litter size. Elucidating the regulatory mechanisms of the natural oestrous cycle in the oviduct under non-fertilisation conditions can improve our understanding of its role in the reproductive system. Herein, whole transcriptome RNA sequencing of oviduct tissue samples was performed. The differentially expressed genes (DEGs) were identified for each time point relative to Day 0 and classified into three clusters based on their expression patterns. Clusters 1 and 2 included genes involved in the physiological changes through the oestrous cycle. Cluster 1 genes were mainly involved in PI3K-Akt signalling and steroid hormone biosynthesis pathways. Cluster 2 genes were involved in extracellular matrix-receptor interactions and protein digestion pathways. In Cluster 3, the DEGs were downregulated in the luteal phase; they were strongly associated with cell cycle, calcium signalling, and oocyte meiosis. The gene expression in the oviduct during the oestrous cycle influenced oocyte transport and fertilisation. Our findings provide a basis for successfully breeding pigs and elucidating the mechanisms underlying the changes in the pig oviduct during the oestrous cycle.

Iodine: Its Role in Thyroid Hormone Biosynthesis and Beyond

The present review deals with the functional roles of iodine and its metabolism. The main biological function of iodine concerns its role in the biosynthesis of thyroid hormones (THs) by the thyroid gland. In addition, however, further biological roles of iodine have emerged. Precisely, due to its significant action as scavenger of reactive oxygen species (ROS), iodine is thought to represent one of the oldest antioxidants in living organisms. Moreover, iodine oxidation to hypoiodite (IO−) has been shown to possess strong bactericidal as well as antiviral and antifungal activity. Finally, and importantly, iodine has been demonstrated to exert antineoplastic effects in human cancer cell lines. Thus, iodine, through the action of different tissue-specific peroxidases, may serve different evolutionarily conserved physiological functions that, beyond TH biosynthesis, encompass antioxidant activity and defense against pathogens and cancer progression.

Tissue-Specific Expression Pattern in Ancherythroculter nigrocauda, a Sexually Size Dimorphic Fish

Certain members of the Actinopterygii class are known to exhibit sexual dimorphism (SD) that results in major phenotypic differences between male and female fishes of a species. One of the most common differences between the two sexes is in body weight, a factor with a high economic value in aquaculture. In this study, we used RNA sequencing (RNA-seq) to study the liver and brain transcriptomes of Ancherythroculter nigrocauda, a fish exhibiting SD. Females attain about fourfold body weight of males at sexual maturity. Sample clustering showed that both sexes were grouped well with their sex phenotypes. In addition, 2,395 and 457 differentially expressed genes (DEGs) were identified in the liver and brain tissues, respectively. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses predicted the association of PPAR signaling, cytochrome P450, and steroid hormone biosynthesis to the differences in sexual size. In addition, weighted gene co-expression network analyses (WGCNA) were conducted, and the green module was identified to be significantly correlated with sexual size dimorphism (SSD). Altogether, these results improve our understanding of the molecular mechanism underlying SSD in A. nigrocauda.