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Ethylene-responsive factors (ERF) play an important role in plant responses to waterlogging stress. However, the function and mechanism of action of ERFVIII in response to waterlogging stress remain poorly understood. In this study, we found that expression of the ERF VIIIa gene CmERF4 in chrysanthemum was induced by waterlogging stress. CmERF4 localized to the nucleus when expressed in tobacco leaves. Yeast two-hybrid and luciferase assays showed that CmERF4 is a transcriptional inhibitor. CmERF4 overexpression in chrysanthemum reduced plant waterlogging tolerance, whereas overexpression of the chimeric activator CmERF4 -VP64 reversed its transcriptional activity, promoting higher waterlogging tolerance than that observed in wild-type plants, indicating that CmERF4 negatively regulates waterlogging tolerance. Transcriptome profiling showed that energy metabolism and reactive oxygen species (ROS) pathway-associated genes were differentially expressed between CmERF4 -VP64 and wild-type plants. RT–qPCR analysis of selected energy metabolism and reactive oxygen species-related genes showed that the gene expression patterns were consistent with the expression levels obtained from RNA-seq analysis. Overall, we identified new functions of CmERF4 in negatively regulating chrysanthemum waterlogging tolerance by modulating energy metabolism and ROS pathway genes. [ABSTRACT FROM AUTHOR]

The TCP transcription factor, comprising the Teosinte branched1/Cycloidea/Proliferating cell factor, plays a crucial role in the regulation of abiotic stresses. The mangrove Avicennia marina thrives in the intertidal zones of coastal areas and exhibits a high degree of salt tolerance. This study aims to explore the molecular mechanisms of the TCPs genes in the adaptation of Avicennia marina to high-saline environments, providing insights into its potential applications in biotechnology and industrial production. A total of 15 AmTCPs were identified from the genome-wide database using bioinformatics methods and were divided into two groups. The cis -regulatory elements analysis of the promoter region revealed significant differences between the same cluster proteins AmTCP8 and AmTCP23, with AmTCP8 having one drought response element and four ABA response elements. Subsequently, AmTCP8 was selected to analyze its biofunction in plant salt tolerance. AmTCP8 was predominantly expressed in both leaves and roots, while salt treatment significantly decreased the expression levels. Transient overexpression of AmTCP8 in tobacco leaves verified that AmTCP8 did not regulate ion transport through Na+ flux, Na/K ratio, or the expression levels of ion homeostasis related genes and osmotic regulation related genes under salt treatment. Instead, AmTCP8 is likely involved in the accumulation of reactive oxygen species (ROS) by downregulating the activity of the ROS scavenging system. In addition, AmTCP8 led to higher expression levels of LOX3 through binding to the promoter of the AmLOX3 gene. In summary, the above results indicated that AmTCP8 is likely a negative regulatory factor for salt tolerance in mangrove A. marina by reducing ROS scavenging ability and promoting ROS accumulation. The results lay the foundation for revealing the biological functions of AmTCP genes in the adaptation of A. marina to high-saline environments, and also provide a reference for studying TCPs genes in other plants. [Display omitted] • Fifteen family members of AmTCPs were identified from mangrove A. marina genome. • Cis -regulatory elements analysis revealed AmTCP8 having drought and ABA response elements. • AmTCP8 does not participate in osmotic and ion homeostasis regulation. • AmTCP8 promotes ROS accumulation by upregulating AmLOX3 and reducing ROS scavenging. • AmTCP8 is a negative regulatory factor for salt tolerance in mangrove A. marina. [ABSTRACT FROM AUTHOR]

Chitosan is an environmentally-friendly active molecule that has been explored for numerous agricultural uses. Its use in crop protection is well-known, however, other properties, such as bioactivity, deserve attention. Moreover, the modes of actions of chitosan remain to be elucidated. The present study assessed the levels of total phenolic compounds, the antioxidant potential, and the expression of reactive oxygen species (ROS) scavenging genes in the berries (skins and seeds), leaves, cluster stems, and shoots upon chitosan application on two red grapevine varieties (Touriga Franca and Tinto Cão). The application of chitosan on the whole vine before and after veraison led to the increased levels of polyphenols, anthocyanins, and tannins in Tinto Cão berries, and polyphenols and tannins in Touriga Franca berries, respectively. CUPric Reducing Antioxidant Capacity (CUPRAC) and Ferric Reducing Antioxidant Power (FRAP) assays indicated an increase in the antioxidant potential of berries. With the exception of ascorbate peroxidase (APX), all the ROS pathway genes tested, i.e., iron-superoxide dismutase (Fe-SOD), copper-zinc-superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione reductase (GR), glutaredoxin (Grx), respiratory burst oxidase (Rboh), amine oxidase (AO), peroxidase (POD) and polyphenol oxidase (PPO), were found up-regulated in chitosan-treated berries. Results from the analyses of leaves, stems, and shoots revealed that chitosan not only induced the synthesis of phenolic compounds but also acted as a facilitator for the transfer of polyphenols from the leaves to the berries.

Gastric cancer is the third most lethal malignancy worldwide. Most gastric cancer patient are discovered at a late or advanced stage, which needed systemic chemotherapy regiments. In this study, we aim to investigate the antitumor activity and mechanisms of 1, 2-di(quinazolin-4-yl)diselane (LG003) against gastric cancer cells. The cell viability, inhibition, apoptosis, DNA damage and ROS levels of gastric cancer cells were measured after treatment with LG003. We identifies anticancer activity of LG003 on gastric cancer and the potential molecular mechanisms. LG003 significantly inhibited cell viability and changed the morphology of gastric cancer cells. Moreover, LG003 induced cell apoptosis and DNA damage via ROS signaling pathway. These results indicates that 1,2-di(quinazolin-4-yl)diselane (LG003) is a antitumor drug candidate that has great potential as a promising agent for therapy in gastric cancer. [ABSTRACT FROM AUTHOR]

Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS) platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

Abstract: Abiotic stress causes diverse biochemical and physiological changes in plants and limits crop productivity. Plants respond and adapt to such stress by altering their cellular metabolism and activating various defense machineries. To understand the molecular basis of stress tolerance in plants, we have developed differential proteomes in a hardy legume, grasspea (Lathyrus sativus L.). Five-week-old grasspea seedlings were subjected independently to high salinity, low temperature and abscisic acid treatment for duration of 36h. The physiological changes of stressed seedlings were monitored, and correlated with the temporal changes of proteome using two-dimensional gel electrophoresis. Approximately, 400 protein spots were detected in each of the stress proteome with one-fourth showing more than 2-fold differences in expression values. Eighty such proteins were subjected to LC–tandem MS/MS analyses that led to the identification of 48 stress-responsive proteins (SRPs) presumably involved in a variety of functions, including metabolism, signal transduction, protein biogenesis and degradation, and cell defense and rescue. While 33 proteins were responsive to all three treatments, 15 proteins were expressed in stress-specific manner. Further, we explored the possible role of ROS in triggering the stress-induced degradation of large subunit (LSU) of ribulose-1,5-bisphosphate carboxylase (Rubisco). These results might help in understanding the spectrum of stress-regulated proteins and the biological processes they control as well as having implications for strategies to improve stress adaptation in plants. [Copyright &y& Elsevier]

Simple Summary: Renal cell carcinoma (RCC) is the eighth leading malignancy in the world, accounting for 4% of all cancers with poor outcome when metastatic. Protein kinases are highly druggable proteins, which are often aberrantly activated in cancers. The aim of our study was to identify candidate targets for metastatic clear cell renal cell carcinoma therapy, using chemo-genomic-based high-throughput screening. We found that the combined inhibition of the CK2 and ATM kinases in renal tumor cells and patient-derived tumor samples induces synthetic lethality. Mechanistic investigations unveil that this drug combination triggers apoptosis through HIF-2α-(Hypoxic inducible factor HIF-2α) dependent reactive oxygen species (ROS) overproduction, giving a new option for patient care in metastatic RCC. Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). A multiplexed assay was used to study the cellular fitness of a panel of engineered ccRCC isogenic 786-O VHL− cell lines in response to a collection of targeted cancer therapeutics including kinase inhibitors, allowing the interrogation of over 2880 drug–gene pairs. Among diverse patterns of drug sensitivities, investigation of the mechanistic effect of one selected drug combination on tumor spheroids and ex vivo renal tumor slice cultures showed that VHL-defective ccRCC cells were more vulnerable to the combined inhibition of the CK2 and ATM kinases than wild-type VHL cells. Importantly, we found that HIF-2α acts as a key mediator that potentiates the response to combined CK2/ATM inhibition by triggering ROS-dependent apoptosis. Importantly, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for a mechanism-based use of combined CK2/ATM inhibitors for improved patient care in metastatic VHL-ccRCC. [ABSTRACT FROM AUTHOR]

Chitosan is an environmentally-friendly active molecule that has been explored for numerous agricultural uses. Its use in crop protection is well-known, however, other properties, such as bioactivity, deserve attention. Moreover, the modes of actions of chitosan remain to be elucidated. The present study assessed the levels of total phenolic compounds, the antioxidant potential, and the expression of reactive oxygen species (ROS) scavenging genes in the berries (skins and seeds), leaves, cluster stems, and shoots upon chitosan application on two red grapevine varieties (Touriga Franca and Tinto Cão). The application of chitosan on the whole vine before and after veraison led to the increased levels of polyphenols, anthocyanins, and tannins in Tinto Cão berries, and polyphenols and tannins in Touriga Franca berries, respectively. CUPric Reducing Antioxidant Capacity (CUPRAC) and Ferric Reducing Antioxidant Power (FRAP) assays indicated an increase in the antioxidant potential of berries. With the exception of ascorbate peroxidase (APX), all the ROS pathway genes tested, i.e., iron-superoxide dismutase (Fe-SOD), copper-zinc-superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione reductase (GR), glutaredoxin (Grx), respiratory burst oxidase (Rboh), amine oxidase (AO), peroxidase (POD) and polyphenol oxidase (PPO), were found up-regulated in chitosan-treated berries. Results from the analyses of leaves, stems, and shoots revealed that chitosan not only induced the synthesis of phenolic compounds but also acted as a facilitator for the transfer of polyphenols from the leaves to the berries. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) secrete exosomes that are capable of modifying the tumor environment through different mechanisms including changes in the cancer-cell secretome. This activity depends on their cargo content that is largely defined by their cellular origin. Endometrial cells are fine regulators of the angiogenic process during the menstrual cycle that includes an angiostatic condition that is associated with the end of the cycle. Hence, we studied the angiogenic activity of menstrual stem cells (MenSCs)-secreted exosomes on prostate PC3 tumor cells. Our results showed that exosomes induce a reduction in VEGF secretion and NF-κB activity. Lower reactive oxygen species (ROS) production in exosomes-treated cells was detected by the DCF method, suggesting that the inhibition of the intracellular ROS impacts both NF-κB and VEGF pathways. We confirmed using tubule formation and plug transplantation assays that MenSCs-exosomes suppress the secretion of pro-angiogenic factors by the PC3 cells in a ROS-dependent manner. The inhibition of the tumor angiogenesis and, consequently, the tumor growth was also confirmed using a xenograft mouse model. Additionally, the anti-tumoral effect was associated with a reduction of tumor hemoglobin content, vascular density and inhibition of VEGF and HIF-1α expression. Importantly, we demonstrate that the exosomes anti-angiogenic effect is specific to the menstrual cell source, as bone marrow MSCs-derived exosomes showed an opposite effect on the VEGF and bFGF expression in tumor cells. Altogether, our results indicate that MenSCs-derived exosomes acts as blockers of the tumor-induced angiogenesis and therefore could be suitable for anti-cancer therapies., Competing Interests: MK is the chief science officer of Cells for Cells and Consorcio Regenero. FA-M, PLG, and ML-V received stipends from Cells for Cells. The other authors declare that they have no competing interests.