Changes In Expression Research Articles

Transcriptomics Reveals Crowding Stress Inhibit the Immune Defense of The Head kidney of The Pearl Gentian Grouper Juvenile through NF-κB Signal Pathway

Crowding stress is a significant welfare factor affecting aquatic animals in recirculating aquaculture systems. Little is known regarding the influence of prolonged crowding stress on the immunity of juvenile pearl gentian groupers. However, research exploring the potential mechanisms through which crowding stress affects fish immune function is limited. Therefore, this study aims to investigate the effect of crowding stress on the immune stress of the pearl gentian grouper juvenile (♀Epinephelus fuscoguttatus × ♂ Epinephelus lanceolatus) under prolonged conditions. We focused on the pearl gentian grouper juvenile and selected low- and high-density groups as the experimental breeding densities. Research shows that crowding stress increases the activities of alkaline acid plum and acid phosphatase, reduces the activities of lysozyme and immunoglobulin M content. RNA sequencing and comparative transcriptomic analyses were employed to explore changes in the gene expression of juvenile pearl gentian groupers subjected to crowding stress. Differential gene expression analyses between the low- and high-density groups identified 5777 unigenes that were differentially expressed following crowding stress, with 3216 and 2561 upregulated and downregulated, respectively. In the GO and KEGG enrichment analyses, many of the enriched signaling pathways related to genes were associated with immunity and oxidative stress. In addition, the combined analyses of enzyme activity and transcriptomics indicated that crowding stress suppressed the immune function of juvenile pearl gentian groupers, reducing their immune ability. Overall, these findings offer new insights into the molecular mechanisms underlying crowding stress tolerance in juvenile pearl gentian grouper, suggesting that the NF-κB pathway plays a crucial role in the immune response of the head kidney of the pearl gentian grouper to long-term crowding stress.

Genes of filter-feeding species as a potential toolkit for monitoring microplastic impacts.

Microplastics (MPs) are ubiquitous in the marine environment and impact organisms at multiple levels. Understanding their actual effects on wild populations is urgently needed. This study develops a toolkit to monitor changes in gene expression induced by MPs in natural environments, focusing on filter-feeding and bioindicator species from diverse ecological and taxonomic groups. Six candidate genes -Caspase, HSP70, HSP90, PK, SOD, and VTG- and nine filter-feeding species -two branchiopods, one copepod, five bivalves and one fish- were selected based on differential expression in response to MPs exposure (mainly the widely used polystyrene and polyethylene polymers) reported in over 30 publications. Some genes are particularly determinant, such as HSP70 and HSP90 (key to managing a wide range of stressors) and SOD (critical for addressing oxidative stress), as they are more directly related to stress. PK is related to carbohydrate metabolism (alterations in energy metabolism); VTG is associated with reproductive problems; Caspase mediates in apoptosis. Each gene in the toolkit plays a role depending on the type of stress assessed, and their combination provides a comprehensive understanding of the impacts of MPs. Differences in gene expressions between species and the exposure thresholds were found. These genes were examined in various scenarios with different types, concentrations, and sizes of MPs, alone or with other stressors. The toolkit offers significant advantages, allowing a comprehensive study of the impact of MPs and focusing on filtering bioindicator species, thus enabling pollution assessment and long-term monitoring. It will outperform traditional methods like tissue counts of MPs where only physical damage is visible, providing a deeper understanding. To our knowledge, this is the first toolkit of its kind.

Dendritic cell activation by iron oxide nanoparticles depends on the extracellular environment.

Nanoparticles can exert immune modulating effects in a host depending on composition, mode of administration, and type of disease. Although the specific mechanisms of nanoparticle-induced immune responses remain unclear, their uptake by macrophages and other phagocytic innate immune cells is considered to be a key event. Our objective here was to ascertain if nanoparticle-mediated activation of dendritic cells (DCs) occurs in vitro or in vivo when exposed to hydroxyethyl starch-coated iron oxide nanoparticles. For the present studies, our choice of nanoparticles, animal model, and experimental design is motivated by our previously published observations that systemic exposure can induce antitumor adaptive immune responses in mouse models of metastatic breast cancer. Here, we began by assessing the potential toxicity of systemic exposure to commercially available starch-coated Bionized Nanoferrite® nanoparticles (BP) by measuring body weight, complete blood count, and enzyme parameters in healthy FVB/NJ mice after repeated BP dosing. We observed no evidence of toxicity at doses up to 25 mg Fe per mouse, five-fold higher than those used in subsequent in vivo experiments. We then measured the expression of surface maturation markers (CD86, MHC II) in DCs incubated with BP in vitro. Although DCs cultured with BP revealed high levels of nanoparticle uptake, neither JAWSII dendritic cells nor bone marrow derived dendritic cells (BMDCs) showed significant changes in marker expression to indicate stimulation of maturation and effector function. To assess whether BP interactions in vivo produced different effects, we analyzed CD80, CD86, and MHC II expression of DCs recovered from the livers, spleens, bone marrows, and lymph nodes of mice injected once with BP (5 mg Fe). Interestingly, only DCs in spleens and bone marrow cells responded to BP exposure. DCs recovered from other organs showed no evidence of increased activation. These findings highlight complex interactions between living systems and nanoparticles, and their potential to mediate context-specific and selective activation of innate immune cells. Our study also emphasizes that results obtained from in vitro experiments must be interpreted with caution, as they may not faithfully represent responses in living systems.

Impact of LITAF on Mitophagy and Neuronal Damage in Epilepsy via MCL-1 Ubiquitination.

This study aims to investigate how the E3 ubiquitin ligase LITAF influences mitochondrial autophagy by modulating MCL-1 ubiquitination, and its role in the development of epilepsy. Employing single-cell RNA sequencing (scRNA-seq) to analyze brain tissue from epilepsy patients, along with high-throughput transcriptomics, we identified changes in gene expression. This was complemented by invivo and invitro experiments, including protein-protein interaction (PPI) network analysis, western blotting, and behavioral assessments in mouse models. Neuronal cells in epilepsy patients exhibited significant gene expression alterations, with increased activity in apoptosis-related pathways and decreased activity in neurotransmitter-related pathways. LITAF was identified as a key upregulated factor, inhibiting mitochondrial autophagy by promoting MCL-1 ubiquitination, leading to increased neuronal damage. Knockdown experiments in mouse models further confirmed that LITAF facilitates MCL-1 ubiquitination, aggravating neuronal injury. Our findings demonstrate that LITAF regulates MCL-1 ubiquitination, significantly impacting mitochondrial autophagy and contributing to neuronal damage in epilepsy. Targeting LITAF and its downstream mechanisms may offer a promising therapeutic strategy for managing epilepsy.

Systemic and immunotoxicity induced by topical application of perfluoroheptane sulfonic acid (PFHpS) or perfluorooctane sulfonic acid (PFOS) in a murine model

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic surfactants of over 12,000 compounds that are incorporated into numerous products for their chemical and physical properties. Studies have associated PFAS with adverse health effects. Although there is a high potential for dermal exposure, these studies are lacking. The present study evaluated the systemic and immunotoxicity of subchronic 28- or 10-days of dermal exposure, respectively, to PFHpS (0.3125–2.5% or 7.82–62.5 mg/kg/dose) or PFOS (0.5% or 12.5 mg/kg/dose) in a murine model. Elevated levels of PFHpS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. PFHpS induced significantly increased relative liver weight, significantly decreased relative spleen and thymus weight, altered serum chemistries, and altered histopathology. Additionally, PFHpS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen of genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells and CD11b+ monocyte and/or macrophages in the spleen along with decreases in eosinophils and dendritic cells in the skin. These findings support PFHpS absorption through the skin leading to liver damage and immune suppression.

The crosstalk between efflux pump and resistance gene mutation in Helicobacter pylori

ABSTRACT Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in Helicobacter pylori. Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.

Astrocyte-derived extracellular matrix proteins regulate synapse remodeling in stress-induced depression.

Major depressive disorder (MDD) is a common mood condition affecting multiple brain regions and cell types. Changes in astrocyte function contribute to depressive-like behaviors. However, while neuronal mechanisms driving MDD have been studied in some detail, molecular mechanisms by which astrocytes promote depression have not been extensively explored. To uncover astrocyte contributions to MDD, we subjected male mice to chronic social defeat stress precipitated by encounters with a dominant male. Animals exposed to this treatment exhibit symptoms indicative of MDD, including reduced social interactions, anxiety, despair, and anhedonia. We then measured astrocyte translating mRNA expression changes in mice that underwent chronic social defeat and control animals using ribosome affinity purification. Bioinformatic analyses reveal significant alterations in the prefrontal cortex (PFC), consistent with previous studies implicating this brain region in MDD. Expression of genes encoding extracellular matrix (ECM) proteins, cell-cell interaction proteins, and proteins controlling glutamatergic synaptic function are significantly altered. These changes correlate with perturbation of glutamatergic transmission, measured by electrophysiology, and increased synaptic cleft size. Among ECM genes, increased expression of mRNA encoding the synaptic remodeling protein s ecreted p rotein a cidic and r ich in c ysteine ( Sparc ) correlates the most with the depressive phenotype. Furthermore, presence of SPARC and other ECM proteins in synaptosomes is also increased and overexpressing Sparc in PFC partially alleviates stress symptoms. Our results raise the possibility that increased expression of Sparc may be a natural protective mechanism against stress-induced synaptic dysfunction in depression.

Alterations in Cellular Gene Expression Due to Co‐Infection With Kaposi's Sarcoma‐Associated Herpesvirus and SARS‐CoV‐2: Implications for Disease Severity

ABSTRACTAn outbreak of the novel coronavirus SARS‐CoV‐2, the causative agent of COVID‐19 pandemic, has resulted in over 7 million confirmed deaths. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal outcomes. Therefore, it is essential to investigate the impact of COVID‐19 on pre‐existing conditions in patients, such as cancer and other infectious diseases. Recent clinical studies have reported the reactivation of human herpesviruses, including Kaposi's sarcoma‐associated herpesvirus (KSHV), in severe COVID‐19 patients or vaccinated individuals. To support these clinical observations, we established a KSHV/SARS‐CoV‐2 co‐infection system in A549‐hACE2 cells. Our findings indicate that co‐infection with live SARS‐CoV‐2 sharply induces KSHV lytic reactivation. Transcriptomic analysis revealed significant changes in global cellular gene expression in KSHV‐infected A549‐hACE2 cells, both with and without SARS‐CoV‐2 co‐infection. These data provide a molecular basis for understanding whether patients with pre‐existing oncogenic herpesvirus infections are at increased risk for more severe COVID‐19 or for developing virus‐associated cancers even after full recovery from COVID‐19.

Enhanced Growth of Cucumber (Cucumis sativus L.) Through Amino Acids and Seaweed Extracts for the Use in Organic Agriculture

AbstractThe increasing consumer interest in organic products is driving the rise of the agricultural sector. However, organic farming productivity was lower than conventional due to the reduction of external inputs, synthetic fertilizers, and pesticides. In this context, the use of organic biostimulant emerged as a promising solution. The aim of this study was to evaluate the efficacy of three doses (0.1, 0.2, 0.3 mL per plant) of an innovative organic biostimulant based on amino acids and seaweed extract (Lombrico® ARREL), on cucumber (Cucumis sativus L.) under hydroponic conditions in a plant growth chamber. The results demonstrated that the root application of the biostimulant promoted plant growth development. In the shoot, there was an increase in height, number of leaves, fresh and dry weight and leaf area compared to the control. In the root, there was an increase in volume (66.2, 83.2, and 165%), fresh weight (45.0, 61.0 and 97.3%) and dry weight (7.0, 23.0 and 53.7%) as escalating the product dose (low, medium and high, respectively) compared to the control. Furthermore, the root length decreased, triggering a significant modification of the root system architecture. Transcriptome analysis in the root revelated that this biostimulant induced change in the gene expression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEEG) analysis showed stimulation of the cell division, biosynthesis and remodeling of the cell wall, increasing plant metabolism and hormone signal transduction, as well as activating the phenylpropanoid biosynthesis. This study showed the benefit of integrating the biostimulant uses in organic agriculture management to improve plant development, thereby enhancing crop productivity.

Miniaturized Liver Disease Mimics to Gain Insights into MMP Expression during Disease Progression.

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions, ranging from hepatic steatosis to steatohepatitis, fibrosis, and severe outcomes such as cirrhosis or cancer. The progression from hepatic steatosis to fibrosis involves significant extracellular matrix (ECM) remodeling, characterized by increased collagen deposition and cross-linking of ECM proteins, causing increased tissue stiffness and altered MMP expression patterns. Dysregulated MMP expression and extracellular acidosis are key contributors to NAFLD progression. Unlike other MMPs, which may be relevant only at specific disease stages, MMP-9 serves as a universal marker, allowing for monitoring of its expression in relation to disease states and ECM parameters. Understanding dysregulated MMP-9 expression across different NAFLD stages can provide crucial insights into disease progression and serve as both a diagnostic and a prognostic biomarker, identifying potential therapeutic targets. This study introduces a three-dimensional (3D) collagen/alginate-based liver disease model designed to investigate how matrix collagen content, elasticity, and diseased cell conditions influence MMP expression and pH levels in situ using nanoprobes. The platform offered an understanding of the relationships between these factors and their role in NAFLD progression, offering valuable insights into disease progression and potential resolution. To examine how various physicochemical and biological factors, particularly MMP expression and collagen deposition, drive NAFLD progression, three 3D NAFLD models were developed, simulating healthy (HL), steatotic (SL), and fibrotic (FL) liver matrices. Additionally, the role of collagenase treatment in the FL matrix in enhancing MMP expression and potentially mitigating fibrosis was also explored. By employing dual-sensitive fluorescent nanoprobes to monitor real-time in situ changes in MMP-9 expression and pH levels, this platform offers a novel approach to understanding the in vitro roles of matrix stiffness, collagen deposition, and diseased cell conditions in NAFLD pathogenesis.

The effect of biosynthesized zinc oxide nanoparticles on gene expression and apoptosis in triple-negative breast cancer cells.

Some forms of breast cancer such as triple-negative phenotype, are serious challenge because of high metastatic cases, high mortality and resistance to conventional therapy motivated the search for alternative treatment approaches. Nanomaterials are promising candidates and suitable alternatives for improving tumor and cancer cell treatments. Biosynthesis of ZnO NPs by help of Berberis integerrima fruit extract, has been done. Analysis of Zinc Oxide NPs using DLS, FTIR, SEM, and EDS techniques have been performed. Moreover, biological activities of ZnO NPs evaluated through MTT method, Flow cytometry, and real time PCR methods. Biocatalytic and apoptotic activity of ZnO NPs on healthy HFF (human fibroblast cell line), MDA-MB 231, and MDA-MB 468 (triple negative breast cancer cell lines, (TNBC)) evaluated. Furthermore, Bax, Bcl-2 and caspase-3 apoptotic genes expression changes in cancer cells assessed in compare to GAPDH as a house keeping gene. Physico-chemical investigation demonstrated ZnO NPs were confirmed by Berberis integerrima fruit extract for the first time. The MTT assay and Flow cytometry results indicated biocompatibility of the ZnO NPs in normal cell line and high anticancer potential against TNBC MDA-MB-231 and MDA-MB-468 cell lines. The IC50 of ZnO NPs were 104.4 and 44.86, 20.96 after 24 hours for HFF, MDA-MB-231 and MDA-MB-468 cells, respectively. The current research showed a fast, cost effective and ecofriendly method for ZnO NPs nanoparticle synthesis. Furthermore, In vitro data analysis demonstrated biocompatibility and highly anticancer effects of biosynthesized ZnO NPs against TNBC cancerous cells.

Changes in MicroRNAs expression mediate molecular mechanism underlying the effect of MeJA on the biosynthesis of podophyllotoxin in Linum album cells

Podophyllotoxin (PTOX), produced by Linum album, is a monolignol that participates in plant defense strategies. Our previous study established that methyl jasmonate (MeJA) significantly stimulates PTOX production in L. album cells. However; the mechanisms by which MeJA regulates PTOX biosynthesis are uncovered. In the present study, we demonstrated that MeJA induces a time-dependent hydrogen peroxide (H2O2) and salicylic acid (SA) accumulation but reduces nitric oxide (NO) generation in L. album cells. PTOX biosynthetic genes such as PAL, CCR, CAD, and PLR were upregulated in response to MeJA exposure. Furthermore, the results of RT-qPCR revealed a positive correlation between the expression of PTOX biosynthetic genes and MeJA-induced upregulation of four miRNAs such as miR156, miR159, miR172, and miR396 at 12 h. Generally, this study revealed that MeJA mediates PTOX biosynthesis in L. album cells by inducing H2O2 and SA formation, which can probably upregulate the expression level of some miRNAs and biosynthetic genes in a redox balance-dependent manner.

Statistical Analysis of Microarray Data to Identify Key Gene Expression Patterns in Primary Hyperoxaluria

This study aims to utilize microarray data deposited by Romero et al. and conduct bioinformatic analysis for identifying differentially expressed genes (DEGs) associated with a novel method involving gene correction at the Alanine–Glyoxylate Aminotransferase (AGXT) locus and direct conversion of fibroblasts from primary hyperoxaluria type 1 (PH1) patients into healthy induced hepatocytes (iHeps) using Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated protein 9 (CRISPR-Cas9) technology. Additionally, the study aims to elucidate the molecular mechanisms underlying hyperoxaluria compared to oxalate crystal formation. Romero et al.'s GSE226019 microarray data was retrieved from Gene Expression Omnibus. Statistical analysis was done in R and Bioconductor, utilizing rigorous methods to ensure robust and reproducible results. The limma program compared gene expression levels across groups. Pathway analysis, protein-protein interaction (PPI) network creation, and miRNA-target interaction network analysis were constructed. The top ten DEGs included ANGPTL3, SLC38A3, KNG1, BDH1, GC, ADH1C, ARG1, CYP3A4, AMBP, and CYP2C9. Enrichment analysis revealed significant associations with various biological pathways, including Linoleic acid metabolism and Retinol metabolism. Volcano plots and mean difference plots highlighted significant gene expression changes between different sample groups. Protein-protein interaction networks and miRNA-target interaction networks provided insights into molecular interactions and regulatory mechanisms. The top ten differentially expressed genes include ANGPTL3, SLC38A3, KNG1, BDH1, GC, ADH1C, ARG1, CYP3A4, AMBP, and CYP2C9—emerge as key players with strong associations to critical biological pathways like Linoleic acid metabolism and drug metabolism-cytochrome P450. Understanding the regulatory role of specific miRNAs (hsa-miR-4501, hsa-miR-5692c, hsa-miR-6731-3p, hsa-miR-6867-5p, hsa-miR-616-3p, hsa-miR-4468, hsa-miR-3692-3p, hsa-miR-4277, hsa-miR-4763-5p, hsa-miR-4797-5p) in gene expression could provide further insights into disease mechanisms and potential therapeutic avenues. The statistical findings provide a foundation for predictive modeling, hypothesis testing, and exploring personalized therapeutic strategies.

Paroxetine promotes longevity via ser-7-dop-4-IIS axis in Caenorhabditis elegans.

Paroxetine, a selective serotonin reuptake inhibitor, is widely used in the clinical treatment of depression. While several antidepressants show promise as geroprotectors, the role of paroxetine in aging remains unclear. In this study, we evaluated the lifespan extension effect of paroxetine in Caenorhabditis elegans (C. elegans) and elucidated the underlying mechanisms. The results showed that paroxetine can prolong lifespan concomitant extension of healthspan as indicated by increasing mobility and reducing lipofuscin accumulation, as well as confer protection to nematodes against different abiotic stresses. Paroxetine upregulated ser-7 expression and downregulated dop-4 expression. dop-4 RNA interference (RNAi) mimicked the beneficial effect of paroxetine on lifespan. Conversely, ser-7 RNAi abolished paroxetine-induced lifespan extension and the expression changes of dop-4 and genes related to insulin/insulin-like growth factor 1 signaling (IIS). Moreover, paroxetine exhibited a comparable lifespan extension effect to that observed in daf-2 or age-1 mutants; however, this effect was abolished in daf-16 mutant. Taken together, these results suggest that paroxetine promotes health and longevity in C. elegans through the ser-7-dop-4-IIS pathway, underscoring its potential as a geroprotector.

Tralokinumab Treatment of Atopic Dermatits Induces A Progressive Transcriptomic Response.

Atopic dermatitis (AD) is characterized by a complex epidermal barrier deficiency and exaggerated immune responses dominated by type-2-mechanisms with variable contributions of additional immune axes. Interleukin (IL)-13 is overexpressed in AD skin and a key driver of both barrier dysfunction and inflammation. We here prospectively studied the effects of IL-13 inhibition with tralokinumab on cutaneous transcriptome profiles using RNA sequencing of biopsies from 16 moderate-to-severe AD patients obtained at baseline, week 2 and week 16. Tralokinumab therapy induced early and delayed expression changes, and progressively shifted the transcriptomic profile of lesional towards non-lesional skin by modulating both genes associated with keratinocyte proliferation and differentiation, itch signaling, and downstream inflammatory responses. At week 16, 751 genes were still significantly dysregulated as compared to healthy control skin, reinforcing the need for long-term immunomodulatory therapy of moderate to severe AD to achieve deep responses. The study was registered with ClinicalTrials.gov (NCT04556461).

CD38 Coordinates with NF-κB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.

Noise exposure is one of the most common causes of sensorineural hearing loss. Although many studies considered inflammation to be a major contributor to noise-induced hearing loss, the process of cochlear inflammation is still unclear. Studies have found that activation of the NF-κB signaling pathway results in the accumulation of macrophages in the inner ear plays an important role in hair cell damage. In this study, tandem mass tag (TMT) technique was used to analyze the changes in basilar membrane proteome expression before and after acoustic injury. After noise exposure, the nicotinamide adenine dinucleotide (NAD) metabolism level was decreased, and the NF-κB signaling pathway was activated. The expression of CD38, the main NAD hydrolase in mammals, may directly lead to inflammation onset. Then, anakinra, an IL-1 receptor blocker, and apigenin, a CD38 inhibitor, were administered to animals to protect against noise-induced hearing loss. Our results showed that anakinra had little influence on the hearing threshold shift, while apigenin significantly reduce the threshold shift of hearing by inhibiting the expression of NF-κB and CD38 can be a promising target for protecting against noise-induced hearing loss.

Adaptive remodeling of rat adrenomedullary stimulus-secretion coupling in a chronic hypertensive environment

Chronic elevated blood pressure impinges on the functioning of multiple organs and therefore harms body homeostasis. Elucidating the protective mechanisms whereby the organism copes with sustained or repetitive blood pressure rises is therefore a topical challenge. Here we address this issue in the adrenal medulla, the master neuroendocrine tissue involved in the secretion of catecholamines, influential hormones in blood pressure regulation. Combining electrophysiological techniques with catecholamine secretion assays on acute adrenal slices from spontaneously hypertensive rats, we show that chromaffin cell stimulus-secretion coupling is remodeled, resulting in a less efficient secretory function primarily upon sustained cholinergic challenges. The remodeling is supported by revamped both cellular and tissular mechanisms. This first includes a decrease in chromaffin cell excitability in response to sustained electrical stimulation. This hallmark was observed both experimentally and in a computational chromaffin cell model, and occurs with concomitant changes in voltage-gated ion channel expression. The cholinergic transmission at the splanchnic nerve-chromaffin cell synapses and the gap junctional communication between chromaffin cells are also weakened. As such, by disabling its competence to release catecholamines in response sustained stimulations, the hypertensive medulla has elaborated an adaptive shielding mechanism against damaging effects of redundant elevated catecholamine secretion and associated blood pressure.

Genome-wide identification, classification, and expression profiling of LAC gene family in sesame

BackgroundLaccases (LACs) are vital plant growth and development enzymes, participating in lignin biopolymerization and responding to stress. However, the role of LAC genes in plant development as well as stress tolerance, is still not well understood, particularly in sesame (Sesamum indicum L.), an important oilseed crop.ResultsIn this study, 51 sesame LAC genes (SiLACs) were identified, which were unevenly distributed across different chromosomes. The phylogeny of Arabidopsis LAC (AtLACs) subdivided the SiLAC proteins into seven subgroups (Groups I-VII), of which Group VII contained only sesame LACs. Within the same subgroup, SiLACs exhibit comparable structures and conserved motifs. The promoter region of SiLACs harbors various cis-acting elements that are related to plant growth, phytohormones, and stress responses. Most SiLACs were expressed in the roots and stems, whereas some were expressed specifically in flowers or seeds. RNA-seq analysis revealed that 19 SiLACs exhibited down-regulation and three showed up-regulation in response to drought stress, while 15 SiLACs were down-regulated and four up-regulated under salt stress. Additionally, qRT-PCR analysis showcased that certain SiLAC expression was significantly upregulated as a result of osmotic and salt stress. SiLAC5 and SiLAC17 exhibited the most significant changes in expression under osmotic and salt stresses, indicating that they may serve as potential targets for improving sesame resistance to various stresses.ConclusionsOur study offers a thorough comprehension of LAC gene structure, classification, evolution, and abiotic stress response in sesame plants. Furthermore, we provide indispensable genetic resources for sesame functional characterization to enhance its tolerance to various abiotic stresses.

Comparative analysis of the LEA gene family in seven Ipomoea species, focuses on sweet potato (Ipomoea batatas L.)

Late Embryogenesis Abundant (LEA) proteins are extensively distributed among higher plants and are crucial for regulating growth, development, and abiotic stress resistance. However, comprehensive data regarding the LEA gene family in Ipomoea species remains limited. In this study, we conducted a genome-wide comparative analysis across seven Ipomoea species, including sweet potato (I. batatas), I. trifida, I. triloba, I. nil, I. purpurea, I. cairica, and I. aquatica, identifying 73, 64, 77, 62, 70, 70, and 74 LEA genes, respectively. The LEA genes were divided into eight subgroups: LEA_1, LEA_2, LEA_3, LEA_4, LEA_5, LEA_6, SMP, and Dehydrin according to the classification of the LEA family in Arabidopsis. Gene structure and protein motif analyses revealed that genes within the same phylogenetic group exhibited comparable exon/intron structures and motif patterns. The distribution of LEA genes across chromosomes varied among the different Ipomoea species. Duplication analysis indicated that segmental and tandem duplications significantly contributed to the expansion of the LEA gene family, with segmental duplications being the predominant mechanism. The analysis of the non-synonymous (Ka) to synonymous (Ks) ratio (Ka/Ks) indicated that the duplicated Ipomoea LEA genes predominantly underwent purifying selection. Extensive cis-regulatory elements associated with stress responses were identified in the promoters of LEA genes. Expression analysis revealed that the LEA gene exhibited widespread expression across diverse tissues and showed responsive modulation to various abiotic stressors. Furthermore, we selected 15 LEA genes from sweet potatoes for RT-qPCR analysis, demonstrating that five genes responded to salt stress in roots, while three genes were responsive to drought stress in leaves. Additionally, expression changes of seven genes varied at different stages of sweet potato tuber development. These findings enhanced our understanding of the evolutionary dynamics of LEA genes within the Ipomoea genome and may inform future molecular breeding strategies for sweet potatoes.

Prolyl hydroxylase domain inhibitors prevent kidney crystal formation by suppressing inflammation.

The early stages of kidney crystal formation involve inflammation and hypoxia-induced cell injury; however, the role of the hypoxic response in kidney crystal formation remains unclear. This study investigated the effects of a prolyl hydroxylase domain inhibitor (roxadustat) on renal calcium oxalate (CaOx) crystal formation through in vitro and in vivo approaches. In the in vitro experiment, murine renal tubular cells (RTCs) were exposed to varying roxadustat concentrations and CaOx crystals. CaOx monohydrate (COM) crystal adhesion was evaluated using fluorescent labels, whereas western blotting was used to examine protein expression. Quantitative real-time polymerase chain reaction was used to analyze gene expression changes. Macrophage responses were investigated by co-culturing them with RTCs treated with COM. In the in vivo experiment, C57BL/6J mice were injected with roxadustat or saline for 2days, followed by glyoxylate for 6days to induce renal crystal deposition. Biochemical measurements recorded plasma erythropoietin, urinary data, and pH levels. Roxadustat suppressed the adhesion of COM crystals to RTCs and the expression of proinflammatory genes, such as chemokine (C-C motif) ligand 2 (Ccl2) and secreted phosphoprotein 1 (Spp1). Roxadustat decreased the expression levels of Ccl2, tumor necrosis factor (Tnf), and interleukin6 (Il6) in co-cultured macrophages. In the in vivo experiment, the amount of renal CaOx crystal deposits was significantly lower in the roxadustat-treated group than in the vehicle group. Roxadustat treatment decreased Ccl2, Tnf, and adheision G protein-coupled receptor E1 (Adgre1) expression in the kidneys. Roxadustat reduced kidney inflammation and CaOx crystal deposition, suggesting its potential as a therapeutic option for kidney stone prevention.