ROS Signaling Research Articles

Enrichment characteristics of Cd and Hg and regulation of heavy metal transporter signaling in Pleurotus ostreatus

Currently, heavy metal pollution has emerged as a global issue. Compared with green plants, edible fungi, significant crops cultivated worldwide, present a greater capacity to accumulate heavy metals (HMs). However, the enrichment characteristics and functions of heavy metal transporters (HMATs) in the accumulation of HMs in edible fungi are still unclear. Cadmium (Cd) and mercury (Hg) are the primary HMs enriched in edible fungi. This study focused on Pleurotus ostreatus, the second largest edible mushroom worldwide, to examine the enrichment process. In this study, a series of different concentrations of CdCl2 and HgCl2 (0, 0.01, 0.05, 0.5, 2, 5, 10, and 20 mg/L) were used to mimic HMs pollution. HMs in the experimental concentration range did not affect the mycelial growth rate or fruiting body yield of P. ostreatus. However, in the 20 mg/L treatment group, the HMs were mainly concentrated in the cap, with about 4.4 mg/kg Cd and 2.7 mg/kg Hg, and were predominantly present in the most toxic ion exchange state. Thirteen HMATs were identified in the genome database of P. ostreatus. Using RT-qPCR, seven HMATs (24093, 1066001, 1106787, 1066344, 1079972, 1095088, and 1104877) whose expression levels were more than twice that of the control under most concentrations of HMs were selected for further investigation of their transport functions and their involvement in signal regulation. Among them, gene 24093 was involved in the absorption of Cd and Hg. These transporters are regulated by ROS, Ca2+, and NO signals under HM stress. This study provides target genes for reducing the risk of HM accumulation through molecular means, and serves as a reference for HM remediation using edible fungi.

Roxadustat Regulates the NKA/Src/HIF-1/ROS Signaling Pathway to Improve Kidney Outcomes in Mice with Lupus

Roxadustat Regulates the NKA/Src/HIF-1/ROS Signaling Pathway to Improve Kidney Outcomes in Mice with Lupus

Identification of systemic nitrogen signaling in foxtail millet (Setaria italica) roots based on split-root system and transcriptome analysis.

The study established split-root system (SRS) in foxtail millet, and identified the molecular regulatory mechanisms and metabolic pathways related to systemic nitrogen signaling based on this system and transcriptome analysis. The growth of crops is primarily constrained by the availability of nitrogen (N), an essential nutrient. Foxtail millet (Setaria italica L.) is a significant orphan crop known for its strong tolerance to barren conditions. Despite this, the signaling pathway of nitrogen in foxtail millet remains largely unexplored. Identifying the candidate genes responsible for nitrogen response in foxtail millet is crucial for enhancing its agricultural productivity. This study utilized the split-root system (SRS) in foxtail millet to uncover genes associated with Systemic Nitrogen Signaling (SNS). Transcriptome analysis of the SRS revealed 2158 differentially expressed genes (DEGs) implicated in SNS, including those involved in cytokinin synthesis, transcription factors, E3 ubiquitin ligase, and ROS metabolism. Silencing of SiIPT5 and SiATL31 genes through RNAi in transgenic plants resulted in reduced SNS response, indicating their role in the nitrogen signaling pathway of foxtail millet. Furthermore, the induction of ROS metabolism-related genes in response to KNO3 of the split-root System (Sp.KNO3) suggests a potential involvement of ROS signaling in the SNS of foxtail millet. Overall, this study sheds light on the molecular regulatory mechanisms and metabolic pathways of foxtail millet in relation to SNS.

Building a Human Ovarian Antioxidant ceRNA Network "OvAnOx": A Bioinformatic Perspective for Research on Redox-Related Ovarian Functions and Dysfunctions.

The ovary is a major determinant of female reproductive health. Ovarian functions are mainly related to the primordial follicle pool, which is gradually lost with aging. Ovarian aging and reproductive dysfunctions share oxidative stress as a common underlying mechanism. ROS signaling is essential for normal ovarian processes, yet it can contribute to various ovarian disorders when disrupted. Therefore, balance in the redox system is crucial for proper ovarian functions. In the present study, by focusing on mRNAs and ncRNAs described in the ovary and taking into account only validated ncRNA interactions, we built an ovarian antioxidant ceRNA network, named OvAnOx ceRNA, composed of 5 mRNAs (SOD1, SOD2, CAT, PRDX3, GR), 10 miRNAs and 5 lncRNAs (XIST, FGD5-AS1, MALAT1, NEAT1, SNHG1). Our bioinformatic analysis indicated that the components of OvAnOx ceRNA not only contribute to antioxidant defense but are also involved in other ovarian functions. Indeed, antioxidant enzymes encoded by mRNAs of OvAnOx ceRNA operate within a regulatory network that impacts ovarian reserve, follicular dynamics, and oocyte maturation in normal and pathological conditions. The OvAnOx ceRNA network represents a promising tool to unravel the complex dialog between redox potential and ovarian signaling pathways involved in reproductive health, aging, and diseases.

Pharmacological Features and Therapeutic Implications of Plumbagin in Cancer and Metabolic Disorders: A Narrative Review.

Plumbagin (PLB) is a naphthoquinone extracted from Plumbago indica. In recent times, there has been a growing body of evidence suggesting the potential importance of naphthoquinones, both natural and artificial, in the pharmacological world. Numerous studies have indicated that PLB plays a vital role in combating cancers and other disorders. There is substantial evidence indicating that PLB may have a significant role in the treatment of breast cancer, brain tumours, lung cancer, hepatocellular carcinoma, and other conditions. Moreover, its potent anti-oxidant and anti-inflammatory properties offer promising avenues for the treatment of neurodegenerative and cardiovascular diseases. A number of studies have identified various pathways that may be responsible for the therapeutic efficacy of PLB. These include cell cycle regulation, apoptotic pathways, ROS induction pathways, inflammatory pathways, and signal transduction pathways such as PI3K/AKT/mTOR, STAT3/PLK1/AKT, and others. This review aims to provide a comprehensive analysis of the diverse pharmacological roles of PLB, examining the mechanisms through which it operates and exploring its potential applications in various medical conditions. In addition, we have conducted a review of the various formulations that have been reported in the literature with the objective of enhancing the efficacy of the compound. However, the majority of the reviewed data are based on in vitro and in vivo studies. To gain a comprehensive understanding of the safety and efficacy of PLB in humans and to ascertain its potential integration into therapeutic regimens for cancer and chronic diseases, rigorous clinical trials are essential. Finally, by synthesizing current research and identifying gaps in knowledge, this review seeks to enhance our understanding of PLB and its therapeutic prospects, paving the way for future studies and clinical applications.

Identifying key genes against rutin on human colorectal cancer cells via ROS pathway by integrated bioinformatic analysis and experimental validation

Colorectal cancer (CRC) poses a significant global health challenge, characterized by substantial prevalence variations across regions. This study delves into the therapeutic potential of rutin, a polyphenol abundant in fruits, for treating CRC. The primary objectives encompass identifying molecular targets and pathways influenced by rutin through an integrated approach combining bioinformatic analysis and experimental validation. Employing Gene Set Enrichment Analysis (GSEA), the study focused on identifying potential differentially expressed genes (DEGs) associated with CRC, specifically those involved in regulating reactive oxygen species, metabolic reprogramming, cell cycle regulation, and apoptosis. Utilizing diverse databases such as GEO2R, CTD, and Gene Cards, the investigation revealed a set of 16 targets. A pharmacological network analysis was subsequently conducted using STITCH and Cytoscape, pinpointing six highly upregulated genes within the rutin network, including TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Gene Ontology (GO) analysis predicted functional categories, shedding light on rutin's potential impact on antioxidant properties. KEGG pathway analysis enriched crucial pathways like metabolic and ROS signaling pathways, HIF1a, and mTOR signaling. Diagnostic assessments were performed using UALCAN and GEPIA databases, evaluating mRNA expression levels and overall survival for the identified targets. Molecular docking studies confirmed robust binding associations between rutin and biomolecules such as TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Experimental validation included inhibiting colorectal cell HT-29 growth and promoting cell growth with NAC through MTT assay. Flow cytometric analysis also observed rutin-induced G1 phase arrest and cell death in HT-29 cells. RT-PCR demonstrated reduced expression levels of target biomolecules in HT-29 cells treated with rutin. This comprehensive study underscores rutin's potential as a promising therapeutic avenue for CRC, combining computational insights with robust experimental evidence to provide a holistic understanding of its efficacy.

Micronutrient deficiency-induced oxidative stress in plants.

Micronutrients like iron (Fe), zinc (Zn), copper (Cu), manganese (Mn), boron (B), nickel (Ni), and molybdenum (Mo) perform significant roles in the regulation of plant metabolism, growth, and development. Micronutrients, namely Fe, Zn, Cu, Mn, and Ni, are involved in oxidative stress and antioxidant defense as they are cofactors or activators of various antioxidant enzymes, viz., superoxide dismutase (Fe, Cu/Zn, Mn, and Ni), catalase (Fe), and ascorbate peroxidase (Fe). An effort has been made to incorporate recent advances along with classical work done on the micronutrient deficiency-induced oxidative stress and associated antioxidant responses of plants. Deficiency of a micronutrient produces ROS in the cellular compartments. Enzymatic and non-enzymatic antioxidant defense systems are often modulated by micronutrient deficiency to regulate redox balance and scavenge deleterious ROS for the safety of cellular constituents. ROS can strike cellular constituents such as lipids, proteins, and nucleic acids and can destruct cellular membranes and proteins. ROS might act as a signaling molecule and activate the antioxidant proteins by interacting with signaling partners such as respiratory burst oxidase homolog (RBOH), G-proteins, Ca2+, mitogen activated protein kinases (MAPKs), and various transcription factors (TFs). Opinions on probable ROS signaling under micronutrient deficiency have been described in this review. However, further research is required to decipher micronutrient deficiency-induced ROS generation, perception, and associated downstream signaling events, leading to the development of antioxidant responses in plants.

Structurally Oriented Carbon Dots as ROS Nanomodulators for Dynamic Chronic Inflammation and Infection Elimination.

The selective elimination of cytotoxic ROS while retaining essential ones is pivotal in the management of chronic inflammation. Co-occurring bacterial infection further complicates the conditions, necessitating precision and an efficacious treatment strategy. Herein, the dynamic ROS nanomodulators are rationally constructed through regulating the surface states of herbal carbon dots (CDs) for on-demand inflammation or infection elimination. The phenolic OH containing CDs derived from honeysuckle (HOCD) and dandelion (DACD) demonstrated appropriate redox potentials, ensuring their ability to scavenge cytotoxic ROS such as ·OH and ONOO-, while invalidity toward essential ones such as O2·-, H2O2, and NO. This enables efficient treatment of chronic inflammation without affecting essential ROS signal pathways. The surface C-N/C═N of CDs derived from taxus leaves (TACD) and DACD renders them with suitable band structures, facilitating absorption in the red region and efficient generation of O2·- upon light irradiation for sterilization. Specifically, the facilely prepared DACD demonstrates fascinating dynamic ROS modulating ability, making it highly suitable for addressing concurrent chronic inflammation and infection, such as diabetic wound infection. This dynamic ROS regulation strategy facilitates the realization of the precise and efficient treatment of chronic inflammation and infection with minimal side effects, holding immense potential for clinical practice.

MdBAM17, a novel member of the β-amylase gene family, positively regulates starch degradation in ALA-induced stomatal opening in apple (Malus × domestica)

5-Aminolevulinic acid (ALA) is a novel plant growth regulator that has shown outstanding capability to promote stomatal opening. Starch degradation, catalyzed by β-amylase (EC3.2.1.2, BAM), plays an important role in stomatal opening. However, whether the starch breakdown is involved in ALA-regulating stomatal movement is unclear. In the current study, we found that exogenous ALA effectively stimulated the starch breakdown in guard cells, increased β-amylase activity and promoted stomatal opening in leaves of apple (Malus × domestica). Based on genome-wide identification, we identified a total of 119 members of BAM gene family in ten commonly Rosaceae crops. Analyses of gene structure, motif identification, and gene pair collinearity revealed relative conservation among members within the same group or subgroup. Among these genes, MdBAM17 and other 12 genes were identified as the orthologous genes of AtBAM1, which is responsible for starch degradation to modulate the stomatal movement in Arabidopsis. RT-qPCR analysis revealed a positive correlation between the expressions of MdBAM17 and stomatal aperture, as well as β-amylase activity, whereas a negative correlation was observed with the starch content. Subcellular localization analysis confirmed that MdBAM17 is a chloroplast protein, consistent with the AtBAM1. MdBAM17 was mainly expressed in guard cells and responsive to exogenous ALA. Overexpressing MdBAM17 increased β-amylase activity and promoted starch breakdown, leading to stomatal opening, which was further strengthened by ALA. RNA-interfering MdBAM17 decreased β-amylase activity, resulting in starch accumulation, and impairing the stomatal opening by ALA. However, modulation of MdBAM17 expression did not affect the levels of flavonols and H2O2 in guard cells, suggesting that MdBAM17-promoted starch degradation may function at downstream of ROS signaling in the ALA-regulated stomatal opening. Our findings provide new insights into the mechanisms of ALA-regulated stomatal movement.

Impact of a biostimulant enriched in betalain degradation products on ROS signaling, proline accumulation, and phytohormone homeostasis

This study investigates the potential of a biostimulant derived from Selenicereus undatus peel waste and enriched in betalain degradation products (BDP), to influence Arabidopsis thaliana seedling development. Notably, lower BDP concentrations enhanced seedling development, while higher dosages exhibited adverse effects. Assessment of mitochondrial activity in both seeds and purified organelles showed that the tested biostimulant did not affect mitochondrial activity or integrity, highlighting its independence from mitochondrial performance. Mechanistically, BDP-enriched biostimulant modulated ROS-signaling, diminishing H2O2 by regulating the enzymatic activity and gene expression of SOD, CAT, GPX, and GR. Particularly, analyzing their different isoform via qRT-PCR, the primary cellular compartment where detoxification occurred were identified. Furthermore, biostimulant was able to influence proline-accumulation, altering both the expression of metabolism (PC5S, P5CR and OAT) and catabolism (PDH and P5CDH) related genes. Finally, the BDP-enriched biostimulant altered phytohormone levels, mainly affecting ABA/ABA-glu, tZea/tZea-rib, and tZea/IAA. Concerning GAs, the increase in GA4 and GA7 suggested an involvement of GA13ox, a hypothesis encouraged by qRT-PCR analysis. In summary, this study underscores the potential of BDP-based biostimulant as sustainable promoters of plant growth, influencing critical regulatory pathways during germination. Further research is necessary to explore their extensive applications in agricultural practices.

Emamectin benzoate exposure induced carp kidney injury by triggering mitochondrial oxidative stress to accelerate ferroptosis and autophagy

Emamectin benzoate (EMB), commonly used as an insecticide in fishery production, inevitably leaves residual chemicals in aquatic environments. High-level EMB exposure can cause severe damage to multiple systems of marine animals, potentially through mechanisms involving severe mitochondrial damage and oxidative stress. However, it is not clear yet how EMB exposure at a certain level can cause damage to fish kidney tissue. In this study, we exposed carps to an aquatic environment containing 2.4 μg/L of EMB and cultured carp kidney cells in vitro, established a cell model exposed to EMB. Our findings revealed that EMB exposure resulted in severe kidney tissue damage in carp and compromised the viability of grass carp kidney cells (CIK cells). By RNA-seq analysis, EMB exposure led to significant differences in mitochondrial homeostasis, response to ROS, ferroptosis, and autophagy signals in carp kidney tissue. Mechanistically, EMB exposure induced mitochondrial oxidative stress by promoting the generation of mitochondrial superoxide and reducing the activity of antioxidant enzymes. Additionally, EMB exposure triggered loss of mitochondrial membrane potential, an imbalance in mitochondrial fusion/division homeostasis, and dysfunction in oxidative phosphorylation, ultimately impairing ATP synthesis. Notably, EMB exposure also accelerated excessive autophagy and ferroptosis of cells by contributing to the formation of lipid peroxides and autophagosomes, and the deposition of Fe2+. However, N-acetyl-L-cysteine (NAC) treatment alleviated the damage and death of CIK cells by inhibiting oxidative stress. Overall, our study demonstrated that EMB exposure induced mitochondrial oxidative stress, impaired mitochondrial homeostasis, and function, promoted autophagy and ferroptosis of kidney cells, and ultimately led to kidney tissue damage in carp. Our research enhanced the toxicological understanding on EMB exposure and provides a model reference for comparative medicine.

Genome-wide analysis of MYB transcription factor family and AsMYB1R subfamily contribution to ROS homeostasis regulation in Avena sativa under PEG-induced drought stress

BackgroundThe myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress.ResultsIn this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage.ConclusionThe results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

Unique regulatory network of dragon fruit simultaneously mitigates the effect of vanadium pollutant and environmental factors.

Under changing climatic conditions, plants are simultaneously facing conflicting stresses in nature. Plants can sense different stresses, induce systematic ROS signals, and regulate transcriptomic, hormonal, and stomatal responses. We performed transcriptome analysis to reveal the integrative stress response regulatory mechanism underlying heavy metal stress alone or in combination with heat and drought conditions in pitaya (dragon fruit). A total of 70 genes were identified from 31,130 transcripts with conserved differential expression. Furthermore, weighted gene co-expression network analysis (WGCNA) identified trait-associated modules. By integrating information from three modules and protein-protein interaction (PPI) networks, we identified 10 interconnected genes associated with the multifaceted defense mechanism employed by pitaya against co-occurring stresses. To further confirm the reliability of the results, we performed a comparative analysis of 350 genes identified by three trait modules and 70 conserved genes exhibiting their dynamic expression under all treatments. Differential expression pattern of genes and comparative analysis, have proven instrumental in identifying ten putative structural genes. These ten genes were annotated as PLAT/LH2, CAT, MLP, HSP, PB1, PLA, NAC, HMA, and CER1 transcription factors involved in antioxidant activity, defense response, MAPK signaling, detoxification of metals and regulating the crosstalk between the complex pathways. Predictive analysis of putative candidate genes, potentially governing single, double, and multifactorial stress response, by several signaling systems and molecular patterns. These findings represent a valuable resource for pitaya breeding programs, offering the potential to develop resilient "super pitaya" plants.

Pathogen resistance was negatively regulated by the NAC transcription factor ScATAF1 in sugarcane

The NAC (NAM, ATAF, and CUC) is one of the largest transcription factor gene families in plants. In this study, 180, 141, and 131 NAC family members were identified from Saccharum complex, including S. officinarum, S. spontaneum, and Erianthus rufipilus. The Ka/Ks ratio of ATAF subfamily was all less than 1. Besides, 52 ATAF members from 12 representative plants were divided into three clades and there was only a significant expansion in maize. Surprisingly, ABA and JA cis-elements were abundant in hormonal response factor, followed by transcriptional regulator and abiotic stressor. The ATAF subfamily was differentially expressed in various tissues, under low temperature and smut pathogen treatments. Further, the ScATAF1 gene, with high expression in leaves, stem epidermis, and buds, was isolated. The encoded protein, lack of self-activation activity, was situated in the cell nucleus. Moreover, SA and JA stresses down-regulated the expression of this gene, while ABA, NaCl, and 4°C treatments led to its up-regulation. Interestingly, its expression in the smut susceptible sugarcane cultivars was much higher than the smut resistant ones. Notably, the colors presented slight brown in tobacco transiently overexpressing ScATAF1 at 1 d after DAB staining, while the symptoms were more obvious at 3 d after inoculation with Ralstonia solanacearum, with ROS, JA, and SA signaling pathway genes significantly up-regulated. We thus speculated ScATAF1 gene could negatively mediate hypersensitive reactions and produce ROS by JA and SA signaling pathways. These findings lay the groundwork for in-depth investigation on the biological roles of ATAF subfamily in sugarcane.

Linking astrocyte metabolism with ROS signalling

Linking astrocyte metabolism with ROS signalling

Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis.

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Exogenous curcumin mitigates As stress in spinach plants: A biochemical and metabolomics investigation

The spinach (S. oleracea L.) was used as a model plant to investigate As toxicity on physio-biochemical processes, exploring the potential mitigation effect of curcumin (Cur) applied exogenously at three concentrations (1, 10, and 20 μM Cur). The employment of Cur significantly mitigated As-induced stress in spinach photosynthetic performance (Fv/Fm, Fo/Fm, and Fv/Fo). Moreover, the co-incubation of Cur with As improved physiological processes mainly associated with plant water systems affected by As stress by recovering the leaf's relative water content (RWC) and osmotic potential (ψπ) nearly to the control level and increasing the transpiration rate (E; 39–59%), stomatal conductivity (gs; 86–116%), and carbon assimilation rate (A; 84–121%) compared to As stressed plants. The beneficial effect of Cur in coping with As-induced stress was also assessed at the plant's oxidative level by reducing oxidative stress biomarkers (H2O2 and MDA) and increasing non-enzymatic antioxidant capacity.Untargeted metabolomics analysis was adopted to investigate the main processes affected by As and Cur application. A multifactorial ANOVA discrimination model (AMOPLS-DA) and canonical correlation analysis (rCCA) were employed to identify relevant metabolic changes and biomarkers associated with Cur and As treatments. The results highlighted that Cur significantly determined the accumulation of glucosinolates, phenolic compounds, and an increase in glutathione redox cycle activities, suggesting an overall elicitation of plant secondary metabolisms. Specifically, the correlation analysis reported a strong and positive correlation between (+)-dihydrokaempferol, L-phenylalanine (precursor of phenolic compounds), and serotonin-related metabolites with antioxidant activities (ABTS and DPPH), suggesting the involvement of Cur application in promoting a cross-talk between ROS signaling and phytohormones, especially melatonin and serotonin, working coordinately to alleviate As-induced oxidative stress. The modulation of plant metabolism was also observed at the level of amino acids, fatty acids, and secondary metabolites synthesis, including N-containing compounds, terpenes, and phenylpropanoids to cooperate with As-induced stress response.

The role of CBL-CIPK signaling in plant responses to biotic and abiotic stresses.

Plants have a variety of regulatory mechanisms to perceive, transduce, and respond to biotic and abiotic stress. One such mechanism is the calcium-sensing CBL-CIPK system responsible for the sensing of specific stressors, such as drought or pathogens. CBLs perceive and bind Calcium (Ca2+) in response to stress and then interact with CIPKs to form an activated complex. This leads to the phosphorylation of downstream targets, including transporters and ion channels, and modulates transcription factor levels and the consequent levels of stress-associated genes. This review describes the mechanisms underlying the response of the CBL-CIPK pathway to biotic and abiotic stresses, including regulating ion transport channels, coordinating plant hormone signal transduction, and pathways related to ROS signaling. Investigation of the function of the CBL-CIPK pathway is important for understanding plant stress tolerance and provides a promising avenue for molecular breeding.

A comparative study on the protective effects of cuminaldehyde, thymoquinone, and gallic acid against carbon tetrachloride-induced pulmonary and renal toxicity in rats by affecting ROS and NF-κB signaling

CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-ҡB, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.

Abstract 1000: Platelets Act As Circulating Reservoir Of Tgfβ1: Role In Abdominal Aortic Aneurysms

Introduction: Transforming Growth Factor-Beta1 (TGFβ1) signaling plays a crucial role in the development and maintenance of the vasculature by orchestrating vascular remodeling signaling cascades. Aberrant TGFβ1 leads to aortic aneurysms, yet there is a persistent conflict in its role in driving or protecting against the degradation of the extracellular matrix (ECM) in abdominal aortic aneurysms (AAA). Notably, limited studies have delved into its cell-specific actions. This ambiguity highlights the need for an improved understanding of the TGFβ1 cell-specific role in AAA. Aims: To elucidate the role of platelet-derived TGFβ1 in AAA development thereon expanding our knowledge on the role of TGFβ1 in vascular remodeling. Methods and Results: Single-cell epitope and transcriptome analysis by using cellular-indexing of transcriptomes and epitopes by sequencing (CITE-seq) of the blood of patients with AAA revealed that platelets were enriched with TGFβ1 compared to healthy individuals. Comparative pathway analysis of the platelet populations showed the association of this cluster with ROS, platelet activation and chemokine signaling pathways that promote AAA pathogenesis. These results were validated in the Apolipoprotein E deficient (ApoE -/- ) mice treated with Angiotensin II for 28 days. To delve into the direct role of platelet-derived TGFβ1 in AAA, we generated mice with conditional knock-down of TGFβ1 in platelets (Tgfb1 flox/flox Pf4 Cre+ ) and subjected these mice to AAA. Remarkably, these mice exhibited reduced aneurysm development and preserved elastin microstructure compared to controls. The expression of phosphorylated smad2/3, one of the downstream TGFβ1-canonical signaling pathways, as well as matrix metalloproteinase, were repressed in the aorta of Tgfb1 flox/flox Pf4 Cre+ mice, suggesting the platelets could supplement Tgfb1 to the aortic tissue sufficient to fuel matrix degradation. These results were recapitulated when the platelets were depleted from the circulation using an anti-GP1b antibody. Conclusion: Our findings reveal that platelets represent an important reservoir of Tgfb1, clarify its cell-specific role in ECM remodeling and underscore its detrimental role in sustaining matrix degradation during AAA.