Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) originates from the nasopharynx epithelium, and luteolin is recognized as an important anti-cancer agent. This study investigated the effects of luteolin on ferroptosis in NPC cells. NPC cells were cultured and exposed to varying concentrations of luteolin. Cell viability, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione (GSH) levels, Fe2+ concentration, and glutathione peroxidase 4 (GPX4) protein level were assessed. Additionally, SRY-related high-mobility-group box 4 (SOX4) expression was measured. Subsequently, the binding of SOX4 to the growth differentiation factor-15 (GDF15) promoter and GDF15 mRNA levels were evaluated. The impact of the SOX4/GDF15 axis on luteolin-induced ferroptosis in NPC cells was assayed. Luteolin treatment induced cell ferroptosis, evidenced by decreased cell viability, increased MDA and Fe2+ levels, and reduced SOD, GSH, and GPX4 levels. Furthermore, luteolin downregulated SOX4 expression, while overexpression of SOX4 reversed luteolin's pro-ferroptotic effects in NPC cells. SOX4 was found to up-regulate GDF15 transcription by directly binding to its promoter. Conversely, overexpression of GDF15 mitigated the ferroptotic effects induced by luteolin in NPC cells. Therefore, luteolin induces ferroptosis in NPC cells via modulation of the SOX4/GDF15 axis. In conclusion, luteolin reduces the binding of SOX4 to the GDF15 promoter by suppressing SOX4 expression, thereby down-regulating GDF15 transcription levels and inducing ferroptosis in NPC cells.

Do SOD2 and SOD3 gene polymorphisms impact the oral health-related quality of life in Para athletes?

The aim of this study was to evaluate whether polymorphisms in SOD2 and SOD3 genes modulate the oral health-related quality of life (OHRQoL) of Para athletes with dental caries experience. The cross-sectional study included 264 Para athletes (143 in athletics, 61 in weightlifting and 60 in swimming). A trained and calibrated team recorded the decayed, missing and filled teeth index (DMFT). The Brazilian version of the Oral Health Impact Profile (OHIP-14) was used to measure OHRQoL. Genomic DNA was extracted from the athletes' saliva, and genetic polymorphisms in the SOD2 (rs5746136 and rs10370) and SOD3 (rs2855262 and rs13306703) genes were analyzed by real-time polymerase chain reaction. Univariate and multivariate analyses were performed. A multivariate General Linear Model analysis, adjusted for sex, revealed that the SOD3 gene polymorphism (rs2855262) had a significant effect on the psychological disability domain [codominant (p = 0.045) and recessive (p=0.038) models]. The SOD2 gene polymorphism (rs5746136) had a significant effect on the total OHIP-14 score [dominant model (p = 0.038)] and the psychological discomfort [dominant model (p = 0.034)] and physical disability [codominant model (p=0.037)] domains. Presence of the SOD2 rs10370 polymorphism led to statistical differences in the total score [codominant (p = 0.026) and dominant (p = 0.023) models] and the handicap domain scores [codominant (p = 0.027) and dominant (p = 0.032) models]. Polymorphisms of the SOD2 and SOD3 genes may be important biomarkers of OHRQoL in Para athletes with dental caries experience.

Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons in the central nervous system (CNS). Mutations in the metalloenzyme SOD1 are associated with inherited forms of ALS and cause a toxic gain of function thought to be mediated by dimer destabilization and misfolding. SOD1 binds two Cu and two Zn ions in its homodimeric form. We have applied native ambient mass spectrometry imaging to visualize the spatial distributions of intact metal-bound SOD1G93A complexes in SOD1G93A transgenic mouse spinal cord and brain sections and evaluated them against disease pathology. The molecular specificity of our approach reveals that metal-deficient SOD1G93A species are abundant in CNS structures correlating with ALS pathology whereas fully metalated SOD1G93A species are homogenously distributed. Monomer abundance did not correlate with pathology. We also show that the dimer-destabilizing post-translational modification, glutathionylation, has limited influence on the spatial distribution of SOD1 dimers.

Function and mechanism of the human SOD2 gene in mice cerebral ischemia/ reperfusion injury.

PURPOSE: To investigate the neuroprotective effects of the SOD2 gene in cerebral ischemia reperfusion injury function and the underlying mechanisms in a mice model of middle cerebral artery ischemia reperfusion. METHODS: SOD2 transgenic mice were engineered using transcription activator-like effector nucleases, and the genotype was identified using PCR after every three generations. Transgenic and C57BL/6J wild type mice were simultaneously subjected to the middle cerebral artery occlusion model. RESULTS: SOD2 expression in the brain, heart, kidney, and skeletal muscle of transgenic mice was significantly higher than that in the wild type. Following ischemia reperfusion, the infarct volume of wild type mice decreased after treatment with fenofibrate compared to the CMC group. Infarction volume in SOD2 transgenic mice after CMC and fenofibrate treatment was significantly reduced. The recovery of cerebral blood flow in wild type mice treated with fenofibrate was significantly enhanced compared with that in the CMC group. CONCLUSIONS: The expression of SOD2 in transgenic mice was significantly higher than that in wild type mice, the neuroprotective role of fenofibrate depends on an increase in SOD2 expression.

CX43 and oxidative stress are the targets of BCB staining to predict the developmental potential of buffalo oocytes.

This study used the brilliant cresyl blue (BCB) staining method to group buffalo oocytes (BCB+ and BCB-) and perform in vitro maturation, in vitro fertilization and embryo culture. At the same time, molecular biology techniques were used to detect gap junction protein expression and oxidative stress-related indicators to explore the molecular mechanism of BCB staining to predict oocyte developmental potential. The techniques of buffalo oocytes to analyse their developmental potential and used immunofluorescence staining to detect the expression level of CX43 protein, DCFH-DA probe staining to detect ROS levels and qPCR to detect the expression levels of the antioxidant-related genes SOD2 and GPX1. Our results showed that the in vitro maturation rate, embryo cleavage rate and blastocyst rate of buffalo oocytes in the BCB+ group were significantly higher than those in the BCB- group and the control group (p < .05). The expression level of CX43 protein in the BCB+ group was higher than that in the BCB- group both before and after maturation (p < .05). The intensity of ROS in the BCB+ group was significantly lower than that in the BCB- group (p < .05), and the expression levels of the antioxidant-related genes SOD2 and GPX1 in the BCB+ group were significantly higher than those in the BCB- group (p < .05). Brilliant cresyl blue staining could effectively predict the developmental potential of buffalo oocytes. The results of BCB staining were positively correlated with the expression of gap junction protein and antioxidant-related genes and negatively correlated with the reactive oxygen species level, suggesting that the mechanism of BCB staining in predicting the developmental potential of buffalo oocytes might be closely related to antioxidant activity.

RBM5 induces motor neuron apoptosis in hSOD1G93A-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by gradual depletion of motor neurons. RNA binding motif protein 5 (RBM5), an abundantly expressed RNA-binding protein, plays a critical role in the process of cellular death. However, little is known about the role of RBM5 in the pathogenesis of ALS. Here, we found that RBM5 was upregulated in ALS hSOD1G93A-NSC34 cell models and hSOD1G93A mice due to a reduction of miR-141-5p. The upregulation of RBM5 increased the apoptosis of motor neurons by inhibiting Rac1-mediated neuroprotection. In contrast, genetic knockdown of RBM5 rescued motor neurons from hSOD1G93A-induced degeneration by activating Rac1 signaling. The neuroprotective effect of RBM5-knockdown was significantly inhibited by the Rac1 inhibitor, NSC23766. These findings suggest that RBM5 could potentially serve as a therapeutic target in ALS by activating the Rac1 signalling.

Muscle-derived IL-1ß regulates EcSOD expression via the NBR1-p62-Nrf2 pathway in muscle during cancer cachexia.

Oxidative stress contributes to the loss of skeletal muscle mass and function in cancer cachexia. However, this outcome may be mitigated by an improved endogenous antioxidant defence system. Here, using the well-established oxidative stress-inducing muscle atrophy model of Lewis lung carcinoma (LLC) in 13-week-old male C57BL/6J mice, we demonstrate that extracellular superoxide dismutase (EcSOD) levels increase in the cachexia-prone extensor digitorum longus muscle. LLC transplantation significantly increased interleukin-1ß (IL-1ß) expression and release from extensor digitorum longus muscle fibres. Moreover, IL-1ß treatment of C2C12 myotubes increased NBR1, p62 phosphorylation at Ser351, Nrf2 nuclear translocation and EcSOD protein expression. Additional studies in vivo indicated that intramuscular IL-1ß injection is sufficient to stimulate EcSOD expression, which is prevented by muscle-specific knockout of p62 and Nrf2 (i.e. in p62 skmKO and Nrf2 skmKO mice, respectively). Finally, since an increase in circulating IL-1ß may lead to unwanted outcomes, we demonstrate that targeting this pathway at p62 is sufficient to drive muscle EcSOD expression in an Nrf2-dependent manner. In summary, cancer cachexia increases EcSOD expression in extensor digitorum longus muscle via muscle-derived IL-1ß-induced upregulation of p62 phosphorylation and Nrf2 activation. These findings provide further mechanistic evidence for the therapeutic potential of p62 and Nrf2 to mitigate cancer cachexia-induced muscle atrophy. KEY POINTS: Oxidative stress plays an important role in muscle atrophy during cancer cachexia. EcSOD, which mitigates muscle loss during oxidative stress, is upregulated in 13-week-old male C57BL/6J mice of extensor digitorum longus muscles during cancer cachexia. Using mouse and cellular models, we demonstrate that cancer cachexia promotes muscle EcSOD protein expression via muscle-derived IL-1ß-dependent stimulation of the NBR1-p62-Nrf2 signalling pathway. These results provide further evidence for the potential therapeutic targeting of the NBR1-p62-Nrf2 signalling pathway downstream of IL-1ß to mitigate cancer cachexia-induced muscle atrophy.

SoDCoD: a comprehensive database of Cu/Zn superoxide dismutase conformational diversity caused by ALS-linked gene mutations and other perturbations.

A structural alteration in copper/zinc superoxide dismutase (SOD1) is one of the common features caused by amyotrophic lateral sclerosis (ALS)-linked mutations. Although a large number of SOD1 variants have been reported in ALS patients, the detailed structural properties of each variant are not well summarized. We present SoDCoD, a database of superoxide dismutase conformational diversity, collecting our comprehensive biochemical analyses of the structural changes in SOD1 caused by ALS-linked gene mutations and other perturbations. SoDCoD version 1.0 contains information about the properties of 188 types of SOD1 mutants, including structural changes and their binding to Derlin-1, as well as a set of genes contributing to the proteostasis of mutant-like wild-type SOD1. This database provides valuable insights into the diagnosis and treatment of ALS, particularly by targeting conformational alterations in SOD1. Database URL: https://fujisawagroup.github.io/SoDCoDweb/.

Arbuscular mycorrhizal fungi enhance drought resistance in Bombax ceiba by regulating SOD family genes.

The physiological activity facilitated by arbuscular mycorrhizal fungi (AMF) contributes to plants' ability to tolerate drought. Nevertheless, it is unclear if AMF colonization affects the expression of genes in the host plant that encode antioxidant enzymes in the superoxide dismutase (SOD) family, which help alleviate drought stress in plants. Here, we conducted a pot trial to determine whether colonization by the AMF Rhizophagus irregularis improves drought resistance in Bombax ceiba. We comprehensively analyzed the SOD gene family and evaluated genome-wide expression patterns of SODs and SOD activity in AMF-colonized and non-mycorrhizal plants under simulated drought. We identified a total of 13 SODs in the genome of B. ceiba, including three FeSODs (BcFSDs), three MnSODs (BcMSDs), and seven Cu/ZnSODs (BcCSDs). Phylogenetic analysis based on binding domain revealed that SOD genes from B. ceiba and various other plant species can be divided into three separate groups, showing significant bootstrap values. Our examination of gene composition and patterns suggests that most BcSOD genes in these three subgroups are significantly conserved. Additionally, it was noted that hormones and stress-responsive cis-regulatory elements were found in all BcSOD promoters. Expression profiling by qRT-PCR demonstrated that AMF increased relative expression levels of Cu/Zn-SODs in both roots and shoots under drought stress, except for BcCSD3 in roots. Furthermore, AMF colonization increased the relative expression of BcMSD1a and BcMSD1b in roots, augmenting SOD activities and increasing ROS scavenging during drought. In general, this work offers molecular evidence in support of the beneficial effect of AMF colonization on drought tolerance in B. ceiba. It also elucidates the expression patterns of SOD genes, which will support efforts to optimize mycorrhizal seedling cultivation under stressful conditions.

Modifiable risk factors, oxidative stress markers, and SOD2 rs4880 SNP in coronary artery disease: an association study.

BACKGROUND: Coronary artery disease (CAD) has been linked to single nucleotide polymorphism (SNP) in superoxide dismutase 2 (SOD 2) gene. Additionally, several modifiable risk factors are also known to influence the CAD risk. AIM: To investigate the association between selected modifiable risk factors and oxidative stress markers with the SOD2 rs4880 SNP in CAD patients. METHODS: A cohort of 150 angiographically confirmed CAD patients, and 100 control subjects in the same geographic area were enrolled. SOD levels and lipid peroxidation were assessed in the blood samples using standard protocols. The genotyping of the SOD2 gene was conducted through the PCR-sequencing method. RESULTS: This study indicated that CAD patients with the rs4880 SNP having heterozygous AG and mutated homozygous GG genotypes have increased oxidative stress, decreased SOD activity, and a positive association with CAD risk (OR 2.85) in comparison with control individuals. The investigation among CAD patients was then carried out based on modifiable risk factors. The risk factors selected were clinical characteristics, physical habits, nutritional status, and body mass index. In all the cases, MDA levels showed a positive association, and SOD activity showed a negative association with the selected polymorphism. CONCLUSIONS: The study suggests that the selected modifiable risk factors have an important role in the higher oxidative stress found in patients, which may lead to SOD2 polymorphism. It also suggests that the SOD2 locus can be identified as a marker gene for CAD susceptibility.

Identification of spontaneous age-related cataract in Microtus fortis. / ä¸œæ–¹ç”°é¼ è‡ªå‘æ€§å¹´é¾„ç›¸å ³æ€§ç™½å† éšœçš„é‰´å®š.

OBJECTIVES: Age-related cataract is the most common type of adult cataract and a leading cause of blindness. Currently, there are few reports on the establishment of animal models for age-related cataract. During the experimental breeding of Microtus fortis (M. fortis), we first observed that M. fortis aged 12 to 15 months could naturally develop cataracts. This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M. fortis. METHODS: The 12-month-old healthy M. fortis were served as a control group and 12-month-old cataractous M. fortis were served as an experimental group. The lens transparency was observed using the slit-lamp biomicroscope. Hematoxylin and eosin staining was used to detect pathological changes in the lens. Biochemical detection methods were applied to detect blood routine, blood glucose levels, the serum activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in both groups. Finally, real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. RESULTS: Compared with the control group, the lens of cataract M. fortis showed severely visible opacity, the structure of lens was destroyed seriously, and some pathological damage, such as swelling, degeneration/necrosis, calcification, hyperplasia, and fiber liquefaction were found in lens epithelial cells (LECs). The fibrous structure was disorganized and irregularly distributed with morgagnian globules (MGs) aggregated in the degenerated lens fibers. There was no statistically significant difference in blood glucose levels between the experimental and control groups (P>0.05). However, white blood cell (WBC) count (P<0.05), lymphocyte count (P<0.01), and lymphocyte ratio (P<0.05) were significantly decreased, while neutrophil percentage (P<0.05) and monocyte ratio (P<0.01) were significantly increased. The serum activities of SOD and GSH-Px (both P<0.05) were both reduced. The mRNAs of cataract-related genes, including CRYAA, CRYBA1, CRYBB3, Bsfp1, GJA3, CRYBA2, MIP, HspB1, DNase2B, and GJA8, were significantly downregultaed in the lenses of the experimental group (all P<0.05). CONCLUSIONS: There are significant differences in lens pathological changes, peroxidase levels, and cataract-related gene expression between cataract and healthy M. fortis. The developed cataract spontaneously in M. fortis is closely related to age, the cataract M. fortis might be an ideal animal model for the research of age-related cataract.

Antifungal Activity and Mechanism of Physcion against Sclerotium rolfsii, the Causal Agent of Peanut Southern Blight.

Peanut southern blight, caused by the soil-borne pathogen Sclerotium rolfsii, is a widespread and devastating epidemic. Frequently, it is laborious to effectively control by labor-intensive foliar sprays of agrochemicals due to untimely find. In the present study, seed treatment with physcion (PHY) at doses of 0.08, 0.16, and 0.32 g AI kg-1 seed significantly improved the growth and photosynthetic activity of peanuts. Furthermore, PHY seed treatment resulted in an elevated enzymatic activity of key enzymes in peanut roots, including peroxidase, superoxide dismutase, polyphenol oxidase, catalase, lipoxygenase, and phenylalanine ammonia-lyase, as well as an increase in callus accumulation and lignin synthesis at the infection site, ultimately enhancing the root activity. This study revealed that PHY seed treatment could promote the accumulation of reactive oxygen species, salicylic acid (SA), and jasmonic acid (JA)/ethylene (ET) in peanut roots, while also decreasing the content of malondialdehyde levels in response to S. rolfsii infection. The results were further confirmed by transcriptome data and metabolomics. These findings suggest that PHY seed treatment activates the plant defense pathways mediated by SA and JA/ET in peanut roots, enhancing the resistance of peanut plants to S. rolfsii. In short, PHY is expected to be developed into a new plant-derived immunostimulant or fungicide to increase the options and means for peanut disease control.

Heavy metals and elderly kidney health: A multidimensional study through Enviro-target Mendelian Randomization.

Chronic Kidney Disease (CKD), closely linked to environmental factors, poses a significant public health challenge. This study, based on 529 triple-repeated measures from key national environmental pollution area and multiple gene-related public databases, employs various epidemiological and bioinformatics models to assess the impact of combined heavy metal exposure (Chromium [Cr], Cadmium [Cd], and Lead [Pb]) on early renal injury and CKD in the elderly. Introducing the novel Enviro-Target Mendelian Randomization method, our research explores the causal relationship between metals and CKD. The findings indicate a positive correlation between increased levels of metal and renal injury, with combined exposure caused renal damage more significantly than individual exposure. The study reveals that metals primarily influence CKD development through oxidative stress and metal ion resistance pathways, focusing on three related genes (SOD2, MPO, NQO1) and a transcription factor (NFE2L2). Metals were found to regulate oxidative stress levels in the body by increasing the expression of SOD2, MPO, NQO1, and decreasing NFE2L2, leading to CKD onset. Our research establishes a new causal inference framework linking environmental pollutants-pathways-genes-CKD, assessing the impact and mechanisms of metal exposure on CKD. Future studies with more extensive in vitro evidence and larger population are needed to validate.

GPCR-Gα13 Involvement in Mitochondrial Function, Oxidative Stress, and Prostate Cancer.

Gα13 and Gα12, encoded by the GNA13 and GNA12 genes, respectively, are members of the G12 family of Gα proteins that, along with their associated Gßγ subunits, mediate signaling from specific G protein-coupled receptors (GPCRs). Advanced prostate cancers have increased expression of GPCRs such as CXC Motif Chemokine Receptor 4 (CXCR4), lysophosphatidic acid receptor (LPAR), and protease activated receptor 1 (PAR-1). These GPCRs signal through either the G12 family, or through Gα13 exclusively, often in addition to other G proteins. The effect of Gα13 can be distinct from that of Gα12, and the role of Gα13 in prostate cancer initiation and progression is largely unexplored. The oncogenic effect of Gα13 on cell migration and invasion in prostate cancer has been characterized, but little is known about other biological processes such as mitochondrial function and oxidative stress. Current knowledge on the link between Gα13 and oxidative stress is based on animal studies in which GPCR-Gα13 signaling decreased superoxide levels, and the overexpression of constitutively active Gα13 promoted antioxidant gene activation. In human samples, mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason grade. However, overexpression of SOD2 in prostate cancer cells yielded conflicting results on cell growth and survival under basal versus oxidative stress conditions. Hence, it is necessary to explore the effect of Gα13 on prostate cancer tumorigenesis, as well as the effect of Gα13 on SOD2 in prostate cancer cell growth under oxidative stress conditions.

Metabolic and Transcriptional Analysis Reveals Flavonoid Involvement in the Drought Stress Response of Mulberry Leaves.

Abiotic stress, especially drought stress, poses a significant threat to terrestrial plant growth, development, and productivity. Although mulberry has great genetic diversity and extensive stress-tolerant traits in agroforestry systems, only a few reports offer preliminary insight into the biochemical responses of mulberry leaves under drought conditions. In this study, we performed a comparative metabolomic and transcriptomic analysis on the "drooping mulberry" (Morus alba var. pendula Dippel) under PEG-6000-simulated drought stress. Our research revealed that drought stress significantly enhanced flavonoid accumulation and upregulated the expression of phenylpropanoid biosynthetic genes. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content were elevated. In vitro enzyme assays and fermentation tests indicated the involvement of flavonol synthase/flavanone 3-hydroxylase (XM_010098126.2) and anthocyanidin 3-O-glucosyltransferase 5 (XM_010101521.2) in the biosynthesis of flavonol aglycones and glycosides, respectively. The recombinant MaF3GT5 protein was found to recognize kaempferol, quercetin, and UDP-glucose as substrates but not 3-/7-O-glucosylated flavonols and UDP-rhamnose. MaF3GT5 is capable of forming 3-O- and 7-O-monoglucoside, but not di-O-glucosides, from kaempferol. This implies its role as a flavonol 3, 7-O-glucosyltransferase. The findings from this study provided insights into the biosynthesis of flavonoids and could have substantial implications for the future diversified utilization of mulberry.

Synthetic lethal CRISPR screen identifies a cancer cell-intrinsic role of PD-L1 in regulation of vulnerability to ferroptosis.

Despite the success of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition in tumor therapy, many patients do not benefit. This failure may be attributed to the intrinsic functions of PD-L1. We perform a genome-wide CRISPR synthetic lethality screen to systematically explore the intrinsic functions of PD-L1 in head and neck squamous cell carcinoma (HNSCC) cells, identifying ferroptosis-related genes as essential for the viability of PD-L1-deficient cells. Genetic and pharmacological induction of ferroptosis accelerates cell death in PD-L1 knockout cells, which are also more susceptible to immunogenic ferroptosis. Mechanistically, nuclear PD-L1 transcriptionally activates SOD2 to maintain redox homeostasis. Lower reactive oxygen species (ROS) and ferroptosis are observed in patients with HNSCC who have higher PD-L1 expression. Our study illustrates that PD-L1 confers ferroptosis resistance in HNSCC cells by activating the SOD2-mediated antioxidant pathway, suggesting that targeting the intrinsic functions of PD-L1 could enhance therapeutic efficacy.

MiR398b Targets Superoxide Dismutase Genes in Soybean in Defense Against Heterodera glycines via Modulating Reactive Oxygen Species Homeostasis.

MicroRNAs play crucial roles in plant defense responses. However, the underlying mechanism by which miR398b contributes to soybean responses to soybean cyst nematode (Heterodera glycines) remains elusive. In this study, by using Agrobacterium rhizogenes-mediated transformation of soybean hairy roots, we observed that miR398b and target genes GmCCS and GmCSD1b played vital functions in soybean-H. glycines interaction. The study revealed that the abundance of miR398b was downregulated by H. glycines infection, and overexpression of miR398b enhanced the susceptibility of soybean to H. glycines. Conversely, silencing of miR398b improved soybean resistance to H. glycines. Detection assays revealed that miR398b rapidly senses stress-induced reactive oxygen species, leading to the repression of target genes GmCCS and GmCSD1b and regulating the accumulation of plant defense genes against nematode infection. Moreover, exogenous synthetic ds-miR398b enhanced soybean sensitivity to H. glycines by modulating H2O2 and O2- levels. Functional analysis demonstrated that overexpression of GmCCS and GmCSD1b in soybean enhanced resistance to H. glycines. RNA interference-mediated repression of GmCCS and GmCSD1b in soybean increased susceptibility to H. glycines. RNA sequencing revealed that a majority of differentially expressed genes in overexpressed GmCCS were associated with oxidative stress. Overall, the results indicate that miR398b targets superoxide dismutase genes, which negatively regulate soybean resistance to H. glycines via modulating reactive oxygen species levels and defense signals.

Exploring Genetic Diversity of SOD2 and POU5F1 for Congenital Heart Disease in the Southwest Chinese Population.

Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies, with atrial septal defect (ASD) and ventricular septal defect (VSD) being the most common forms of simple CHD, which involve a large number of susceptibility genes. However, despite extensive research, the etiology of ASD and VSD remains unclear. Yunnan Province has advantages in exploring CHD pathogenesis due to its unique genetic background. Therefore, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of genes and susceptibility to simple CHD in a specific population by means of a case-control study. A total of 337 healthy controls and 767 patients with simple CHD (501 ASD and 266 VSD) from China were recruited. Candidate SNPs were identified through whole-genome sequencing of pooled CHD patients and controls (pool-seq). Genotyping from 1,104 samples was performed, and stratified analysis was conducted to explore the association between positive SNPs and CHD subtypes. χ2 tests and logistic regression were used to analyze the relationship between each SNP and simple CHD. Of 11 SNPs identified, SOD2 rs62437333 (P = 0.005) and POU5F1 rs3130504 (P = 0.017) showed differences between the control and ASD cohorts. In the dominant inheritance model hypothesis, rs62437333 allele C carriers had increased ASD (odds ratio (OR) = 2.04, P = 0.005) and combined simple CHD risk (OR = 2.33, P = 0.012) compared to DD genotype, while rs3130504 allele C carriers had increased ASD risk (OR = 1.121, P = 0.045) compared to DD genotype.

The hard life of an octopus embryo is seen through gene expression, energy metabolism, and its ability to neutralize radical oxygen species.

The reproductive process in Octopus maya was analyzed to establish the amount of reactive oxygen species that the embryos inherit from females, during yolk synthesis. At the same time, respiratory metabolism, ROS production, and the expression of some genes of the antioxidant system were monitored to understand the ability of embryos to neutralize maternal ROS and those produced during development. The results indicate that carbonylated proteins and peroxidized lipids (LPO) were transferred from females to the embryos, presumably derived from the metabolic processes carried out during yolk synthesis in the ovary. Along with ROS, females also transferred to embryos glutathione (GSH), a key element of the antioxidant defense system, thus facilitating the neutralization of inherited ROS and those produced during development. Embryos are capable of neutralizing ROS thanks to the early expression of genes such as catalase (CAT) and superoxide dismutase (SOD), which give rise to the synthesis of enzymes when the circulatory system is activated. Also, it was observed that the levels of the routine metabolic rate of embryos are almost as high as those of the maximum activity metabolism, which leads, on the one hand, to the elevated production of ROS and suggests that, at this stage of the life cycle in octopuses, energy production is maximum and is physically limited by the biological properties inherent to the structure of embryonic life (oxygen transfer through the chorion, gill surface, pumping capacity, etc.). Due to its role in regulating vascularization, a high expression of HIf-1A during organogenesis suggests that circulatory system development has begun in this phase of embryo development. The results indicate that the routine metabolic rate and the ability of O. maya embryos to neutralize the ROS are probably the maximum possible. Under such circumstances, embryos cannot generate more energy to combat the free radicals produced by their metabolism, even when environmental factors such as high temperatures or contaminants could demand excess energy.

Induction of necrosis symptoms by potato virus X in AGO2-silenced tomato plants associates with reduced transcript accumulation of copper chaperon for superoxide dismutase gene.

RNA silencing is a prominent antiviral defense mechanism in plants. When infected with a virus, RNA silencing-deficient plants tend to show exacerbated symptoms along with increased virus accumulation. However, how symptoms are exacerbated is little understood. Here, we investigated the role of the copper chaperon for superoxide dismutase (CCS) 1, in systemic necrosis observed in Argonaute (AGO)2-silenced tomato plants infected with potato virus X (PVX). While infection with the UK3 strain of PVX induced mosaic symptoms in tomato plants, systemic necrosis occurred when AGO2 was silenced. The CCS1 mRNA level was reduced and micro RNA398 (miR398), which potentially target CCS1, was increased in AGO2-knockdown tomato plants infected with PVX-UK3. Ectopic expression of CCS1 using recombinant PVX attenuated necrosis, suggesting that CCS1 alleviates systemic necrosis by activating superoxide dismutases to scavenge reactive oxygen species. Previous reports have indicated a decrease in the levels of CCS1 and superoxide dismutases along with an increased level of miR398 in plants infected with other viruses and viroids, and thus might represent shared regulatory mechanisms that exacerbate symptoms in these plants.