Multi-environment Evaluations Across Ecological Regions Reveal That the Kernel Oil Content of Cottonseed Is Equally Determined by Genotype and Environment.

Cotton is the fifth-largest oil crop in the world. A high kernel oil content (KOC) and high stability are important cottonseed attributes for food security. In this study, the phenotype of KOC and the genotype-by-environment interaction factors were collectively dissected using 250 recombinant inbred lines, their parental cultivars sGK156 and 901-001, and CCRI70 across multi-environments. ANOVA and correlation analysis showed that both genotype and environment contributed significantly to KOC accumulation. Analyses of additive main effect multiplicative interaction and genotype-by-environment interaction biplot models presented the effects of genotype, environment, and genotype by environment on KOC performance and the stability of the experimental materials. Interaction network analysis revealed that meteorological and geographical factors explained 38% of the total KOC variance, with average daily rainfall contributing the largest positive impact and cumulative rainfall having the largest negative impact on KOC accumulation. This study provides insight into KOC accumulation and could direct selection strategies for improved KOC and field management of cottonseed in the future.

Network-driven targeted analysis reveals that Astragali Radix alleviates doxorubicin-induced cardiotoxicity by maintaining fatty acid homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) is a popular traditional Chinese medicine that has been used for more than 2000 years. It is a well-known tonic for weak people with chronic diseases, such as heart failure and cerebral ischemia. Previous studies have reported that AR could support the "weak heart" of cancer patients who suffered from doxorubicin (DOX)-induced cardiotoxicity (DIC). However, the underlying mechanism remains unclear. AIM OF THE STUDY: This study aimed to uncover the critical pathways and molecular determinants for AR against DIC by fully characterizing the network-based relationship. MATERIALS AND METHODS: We integrated ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) profiling, database and literature searching, and the human protein-protein interactome to discover the specific network module associated with AR against DIC. To validate the network-based findings, a low-dose, long-term DIC mouse model and rat cardiomyoblast H9c2 cells were employed. The levels of potential key metabolites and proteins in hearts and cells were quantified by the LC-MS/MS targeted analysis and western blotting, respectively. RESULTS: We constructed one of the most comprehensive AR component-target network described to date, which included 730 interactions connecting 64 unique components and 359 unique targets. Relying on the network-based evaluation, we identified fatty acid metabolism as a putative critical pathway and peroxisome proliferator-activated receptors (PPARα and PPARγ) as potential molecular determinants. We then confirmed that DOX caused the accumulation of fatty acids in the mouse failing heart, while AR promoted fatty acid metabolism and preserved heart function. By inhibiting PPARγ in H9c2 cells, we further found that AR could alleviate DIC by activating PPARγ to maintain fatty acid homeostasis. CONCLUSIONS: Our findings imply that AR is a promising drug candidate that treats DIC by maintaining fatty acid homeostasis. More importantly, the network-based method developed here could facilitate the mechanism discovery of AR therapy and help catalyze innovation in its clinical application.

Identification and analysis of oil candidate genes reveals the molecular basis of cottonseed oil accumulation in Gossypium hirsutum L.

KEY MESSAGE: Based on the integration of QTL-mapping and regulatory network analyses, five high-confidence stable QTL regions, six candidate genes and two microRNAs that potentially affect the cottonseed oil content were discovered. Cottonseed oil is increasingly becoming a promising target for edible oil with its high content of unsaturated fatty acids. In this study, a recombinant inbred line (RIL) cotton population was constructed to detect quantitative trait loci (QTLs) for the cottonseed oil content. A total of 39 QTLs were detected across eight different environments, of which five QTLs were stable. Forty-three candidate genes potentially involved in carbon metabolism, fatty acid synthesis and triacylglycerol biosynthesis processes were further obtained in the stable QTL regions. Transcriptome analysis showed that nineteen of these candidate genes expressed during  the developing cottonseed ovules and may affect the cottonseed oil content. Besides, transcription factor (TF) and microRNA (miRNA) co-regulatory network analyses based on the nineteen candidate genes suggested that six genes, two core miRNAs (ghr-miR2949b and ghr-miR2949c), and one TF GhHSL1 were considered to be closely associated with the cottonseed oil content. Moreover, four vital genes were validated by quantitative real-time PCR (qRT-PCR). These results provide insights into the oil accumulation mechanism in developing cottonseed ovules through the construction of a detailed oil accumulation model.

Attenuation of doxorubicin-induced oxidative damage in rat brain by regulating amino acid homeostasis with Astragali Radix.

The nervous system disorders caused by doxorubicin (DOX) are among the severe adverse effects that dramatically reduce the quality of life of cancer survivors. Astragali Radix (AR), a popular herbal drug and dietary supplement, is believed to help treat brain diseases by reducing oxidative stress and maintaining metabolic homeostasis. Here we show the protective effects of AR against DOX-induced oxidative damage in rat brain via regulating amino acid homeostasis. By constructing a clinically relevant low-dose DOX-induced toxicity rat model, we first performed an untargeted metabolomics analysis to discover specific metabolic features in the brain after DOX treatment and AR co-treatment. It was found that the amino acid (AA) metabolism pathways altered most significantly. To accurately characterize the brain AA profile, we established a sensitive, fast, and reproducible hydrophilic interaction chromatography-tandem mass spectrometry method for the simultaneous quantification of 22 AAs. The targeted analysis further confirmed the changes of AAs between different groups of rat brain. Specifically, the levels of six AAs, including glutamate, glycine, serine, alanine, citrulline, and ornithine, correlated (Pearson |r| > 0.47, p < 0.05) with the brain oxidative damage that was caused by DOX and rescued by AR. These findings present that AAs are among the regulatory targets of DOX-induced brain toxicity, and AR is a promising therapeutic agent for it.

[Effects of hydroxy safflor yellow A on blood vessel and mRNA expression with VEGF and bFGF of transplantation tumor with gastric adenocarcinoma cell line BGC-823 in nude mice].

OBJECTIVE: To investigate the effects of Hydroxy Safflor yellow A (HSYA) on the growth of blood vessel of transplantation tumor of gastric adenocarcinoma cell line BGC-823 in nude mice and its underlying mechanism of antagonizing tumor angiogenesis. METHOD: The BGC-823 cells was subcutaneouly injected into the right anterior armpit of BALB/C nu/nu nude mice and established the animal model of transplantation tumor. Then nude mice were divided into 4 groups at random: model group, control group, high or low dosage of HSYA group. The model group were treated with normal sodium by intraperitoneal injection, HSYA groups were treated with HSYA at concentration of 0.056 g x L(-1) and 0.028 g x L(-1) by intraperitoneal injection, and in these groups each mouse was injected 2 times everyday with 0.2 mL by 4-6 hours interval. The control group were injected in enterocoelia 1 times every 2 days starting from the third day with cytoxan at 2 g x L(-1). 20 days later, the volume and weight of nude mice were observed. The pathological change of tumor tissue was observed under optical microscope. The mRNA expression of VEGF and bFGF of transplantation tumor were detected by real time quantitative PCR. RESULT: The volume (607.42 +/- 252.96) mm3, weight (0.88 +/- 0.14) g of transplantation tumor, the mRNA expression level of VEGF 0.49 +/- 0.13 and bFGF 0.60 +/- 0.48 are reduced significantly after treatment with HSYA at the concentration of 0.028 g x L(-1) compared with physiologic saline-treated group (P < 0.05 or P < 0.01). The tumor pathological angiogenesis of HSYA group is also less obvious than the normal sodium-treated group. CONCLUSION: HSYA in given concentration can inhibit the growth of BGC-823 transplantation tumor, and decreasing the mRNA expression of VEGF and bFGF, which suggests that inhibiting tumor angiogenesis may be one of the mechanisms of HSYA antagonizing tumor.

[Effects of pingyu capsule on signal transduction of rats with chronic stress-induced depression].

OBJECTIVE: To observe the effects of Pingyu capsule on such important regulatory factors as cAMP, PKA and PKC of the signal transduction in rats with chronic stress-induced depression. METHOD: Wistar male rats were randomly divided into control group, model group, paroxetine group, and Pingyu capsule low, middle and high doses groups; rats in all groups but the control group were fed in single cage for 21 days and were given such irritations as lightening stroke on pelma, ice water swimming, pyretic fumigation and tail clipping during this period; lobe cortex and hippocampus of all rats were taken out for detection of the cAMP content by means of radioactive immunization, PKA and PKC content by Elisa, and the PKA and PKC activity by radioactive isotope. RESULT: Content of cAMP in lobe cortex and hippocampus, content and activity of PKA in hippocampus, and content of PKC in lobe cortex of rats in the model group were lower than those in the normal group. Pingyu capsule and paroxetine can increase them. CONCLUSION: The anti-depression effect of Pingyu capsule maybe related to its function of adjusting the signal transduction of cAMP-PKA.

Identification and genetic analysis of human and mouse activated Cdc42 interacting protein-4 isoforms.

By yeast two-hybrid screening with the Src kinase Lyn as bait, we identified a novel gene product with features of a scaffolding protein. Reported as Felic ( es-related, with homology to Ezrin, Lyn interactor with Cdc42), it is related to the CIP4 (Cdc42 Interacting Protein-4) gene. Southern blotting for CIP4/Felic of genomic DNA shows a single band, suggesting no gene duplication. Felic differs from CIP4 because of a 29 nucleotide sequence derived from the end of intron 13. Consequently, there is an out-of-frame translation that destroys an SH3 domain. Analysis of various tissues shows that the original CIP4 is the predominant transcript. Therefore, we propose to call that, CIP4a and Felic, CIP4b. During screening of the colorectal CaCo2 cell line, clones corresponding to a third CIP4-related transcript (CIP4c) were identified. CIP4c encodes a premature stop codon, resulting in the loss of the SH3 domain. A fourth, relatively abundant transcript (CIP4h) was isolated from heart, lung, and trachea tissue. CIP4h retains the SH3 domain. CIP4 levels are modified by all-trans-retinoic acid. The presence of alternative splice transcripts, with or without SH3 domains, suggests that CIP4 regulates cytoskeletal organization through structural-functional differences in a tissue-specific manner.