RESUMEN
Adventitious root (AR) formation is a limiting factor in the vegetative propagation of tree peony (Paeonia suffruticosa Andr.). PoARRO-1, which encodes an auxin oxidase involved in AR formation, plays a role in the root development of P. ostii, but its associated molecular regulatory mechanisms are not yet understood. In this study, we examined the role of PoARRO-1 in AR formation in P. ostii. The overexpression of PoARRO-1 in P. ostii test-tube plantlets led to a notable enhancement in both the rooting rate and the average number of ARs in vitro, as well as increased activities of peroxidase (POD), superoxide dismutase (SOD), and indoleacetic acid oxidase (IAAO). PoARRO-1 was involved in the conversion of IAA-Asp and IAA-Glu to OxIAA and promoted IAA oxidation. RNA sequencing analysis revealed that PoARRO-1 overexpression led to upregulation of enzyme activity, auxin metabolism related genes. Further analyses showed that PoARRO-1 interacted with the 1-175 aa position of PoIAA27b to regulate the formation of ARs. We therefore propose that PoARRO-1 interacts with PoIAA27b to promote AR formation, and it may be useful targets for enhancing the in vitro propagation of P. ostii.
Asunto(s)
Ácidos Indolacéticos , Paeonia , Proteínas de Plantas , Raíces de Plantas , Paeonia/genética , Paeonia/metabolismo , Paeonia/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ácidos Indolacéticos/metabolismo , Regulación de la Expresión Génica de las Plantas , PeroxidasasRESUMEN
Drought is a major environmental stress that limits plant growth, so it's important to identify drought-responsive genes to understand the mechanism of drought response and breed drought-tolerant roses. Protein phosphatase 2C (PP2C) plays a crucial role in plant abiotic stress response. In this study, we identified 412 putative PP2Cs from six Rosaceae species. These genes were divided into twelve clades, with clade A containing the largest number of PP2Cs (14.1%). Clade A PP2Cs are known for their important role in ABA-mediated drought stress response; therefore, the analysis focused on these specific genes. Conserved motif analysis revealed that clade A PP2Cs in these six Rosaceae species shared conserved C-terminal catalytic domains. Collinearity analysis indicated that segmental duplication events played a significant role in the evolution of clade A PP2Cs in Rosaceae. Analysis of the expression of 11 clade A RcPP2Cs showed that approximately 60% of these genes responded to drought, high temperature, and salt stress. Among them, RcPP2C24 exhibited the highest responsiveness to both drought and ABA. Furthermore, overexpression of RcPP2C24 significantly reduced drought tolerance in transgenic tobacco by increasing stomatal aperture after exposure to drought stress. The transient overexpression of RcPP2C24 weakened the dehydration tolerance of rose petal discs, while its silencing increased their dehydration tolerance. In summary, our study identified PP2Cs in six Rosaceae species and highlighted the negative role of RcPP2C24 on rose's drought tolerance by inhibiting stomatal closure. Our findings provide valuable insights into understanding the mechanism behind rose's response to drought.
Asunto(s)
Sequías , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Proteína Fosfatasa 2C , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Deshidratación/genética , Resistencia a la Sequía , Nicotiana/genética , Nicotiana/fisiología , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Proteína Fosfatasa 2C/genética , Proteína Fosfatasa 2C/metabolismo , Rosaceae/enzimología , Rosaceae/genética , Estrés Fisiológico/genéticaRESUMEN
Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.
Asunto(s)
Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Inmunoterapia Adoptiva/métodos , Microambiente Tumoral/inmunología , Animales , Inmunoterapia/métodosRESUMEN
The use of nanomaterials in gene editing and synthetic biology has emerged as a pivotal strategy in the pursuit of refined treatment methodologies for pulmonary disorders. This review discusses the utilization of nanomaterial-assisted gene editing tools and synthetic biology techniques to promote the development of more precise and efficient treatments for pulmonary diseases. First, we briefly outline the characterization of the respiratory system and succinctly describe the principal applications of diverse nanomaterials in lung ailment treatment. Second, we elaborate on gene-editing tools, their configurations, and assorted delivery methods, while delving into the present state of nanomaterial-facilitated gene-editing interventions for a spectrum of pulmonary diseases. Subsequently, we briefly expound on synthetic biology and its deployment in biomedicine, focusing on research advances in the diagnosis and treatment of pulmonary conditions against the backdrop of the coronavirus disease 2019 pandemic. Finally, we summarize the extant lacunae in current research and delineate prospects for advancement in this domain. This holistic approach augments the development of pioneering solutions in lung disease treatment, thereby endowing patients with more efficacious and personalized therapeutic alternatives.
Asunto(s)
COVID-19 , Edición Génica , Enfermedades Pulmonares , Nanoestructuras , Biología Sintética , Edición Génica/métodos , Humanos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/terapia , Biología Sintética/métodos , COVID-19/terapia , COVID-19/genética , Animales , Sistemas CRISPR-Cas , SARS-CoV-2/genética , Terapia Genética/métodosRESUMEN
Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.
Asunto(s)
Disbiosis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/microbiología , Disbiosis/metabolismo , Disbiosis/microbiología , Disbiosis/inmunología , Humanos , Ratones , Masculino , Femenino , Animales , Enfermedad del Almacenamiento de Glucógeno Tipo I/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Modelos Animales de Enfermedad , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologíaRESUMEN
Cellular senescence is a significant risk factor for aging and age-related diseases (ARD). The canonical senolytics Dasatinib and Quercetin (DQ) have shown promise in clearing senescent cells (SnCs); however, the lack of selectivity poses a challenge in achieving optimal outcomes. Despite the recent occurrence of nanomaterial-based approaches targeting SnCs, limited therapeutic effects, and potential toxicity still remain a major concern. Herein, a "double locks-like" nanoplatform is developed that integrated Galactan coating and mesoporous polydopamine to encase the senolytic drug DQ. By this way, DQ is only released in SnCs that are featured with higher levels of ß-galactosidase (ß-gal) and low PH. Additionally, the nanoparticles are equipped with 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) to gain enhanced photothermal converting potential. Consequently, the synthesized nanosenolytics demonstrate remarkable specificity and efficacy in eradicating SnCs, and accordingly reverse pulmonary fibrosis in mice without affecting normal tissues. Upon exposure of near-infrared (NIR) light, the nanoparticles demonstrate to efficiently remove senescent tumor cells inducted by chemotherapy, thereby hindering the outgrowth and metastasis or breast cancer. Collectively, the present study develops an "On/Off" switchable nanoplatform in response to SnCs, and produces a more safe, efficient, and feasible way to delay aging or alleviate age-associated diseases.
RESUMEN
Endometrial cancer (EC) is a frequently diagnosed gynecologic cancer. Identifying reliable prognostic genes for predicting EC onset is crucial for reducing patient morbidity and mortality. Here, a comprehensive strategy with transcriptomic and proteomic data was performed to measure EC's characteristics. Based on the publicly available RNA-seq data, death-associated protein kinase 3, recombination signal-binding protein for the immunoglobulin kappa J region, and myosin light chain 9 were screened out as potential biomarkers that affect the EC patients' prognosis. A linear model was further constructed by multivariate Cox regression for the prediction of the risk of being malignant. From further integrative analysis, exosomes were found to have a highly enriched role that might participate in EC occurrence. The findings were validated by qRT-polymerase chain reaction (PCR) and western blotting. Collectively, we constructed a prognostic-gene-based model for EC prediction and found that exosomes participate in EC incidents, revealing significantly promising support for the diagnosis of EC.
RESUMEN
Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.
Asunto(s)
Lesión Pulmonar Aguda , Plantas Medicinales , Neumonía Viral , Neumonía , Ratones , Animales , Macrófagos Alveolares/metabolismo , Pulmón/metabolismo , Neumonía Viral/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Mitocondrias/patología , Ácido gamma-Aminobutírico/metabolismo , Neumonía/metabolismoRESUMEN
Despite accumulating evidence linking defective lysosome function with autoimmune diseases, how the catabolic machinery is regulated to maintain immune homeostasis remains unknown. Late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (Lamtor5) is a subunit of the Ragulator mediating mechanistic target of rapamycin complex 1 (mTORC1) activation in response to amino acids, but its action mode and physiological role are still unclear. Here it is demonstrated that Lamtor5 level is markedly decreased in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE). In parallel, the mice with myeloid Lamtor5 ablation developed SLE-like manifestation. Impaired lysosomal function and aberrant activation of mTORC1 are evidenced in Lamtor5 deficient macrophages and PBMCs of SLE patients, accompanied by blunted autolysosomal pathway and undesirable inflammatory responses. Mechanistically, it is shown that Lamtor5 is physically associated with ATP6V1A, an essential subunit of vacuolar H+-ATPase (v-ATPase), and promoted the V0/V1 holoenzyme assembly to facilitate lysosome acidification. The binding of Lamtor5 to v-ATPase affected the lysosomal tethering of Rag GTPase and weakened its interaction with mTORC1 for activation. Overall, Lamtor5 is identified as a critical factor for immune homeostasis by intergrading v-ATPase activity, lysosome function, and mTOR pathway. The findings provide a potential therapeutic target for SLE and/or other autoimmune diseases.
Asunto(s)
Autoinmunidad , Lupus Eritematoso Sistémico , Lisosomas , ATPasas de Translocación de Protón Vacuolares , Animales , Femenino , Humanos , Ratones , Autoinmunidad/inmunología , Autoinmunidad/genética , Modelos Animales de Enfermedad , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Lisosomas/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , ATPasas de Translocación de Protón Vacuolares/metabolismo , ATPasas de Translocación de Protón Vacuolares/genética , ATPasas de Translocación de Protón Vacuolares/inmunologíaRESUMEN
Non-antibiotic strategies are desperately needed to treat post-traumatic osteomyelitis (PTO) due to the emergence of superbugs, complex inflammatory microenvironments, and greatly enriched biofilms. Previously, growing evidence indicated that quorum sensing (QS), a chemical communication signal among bacterial cells, can accelerate resistance under evolutionary pressure. This study aims to develop a medical dressing to treat PTO by inhibiting QS and regulating the inflammatory microenvironment, which includes severe oxidative stress and acid abscesses, through a reactive oxygen species (ROS)-responsive bond between N1- (4-borobenzoyl)-N3-(4-borobenzoyl)-the N1, the N1, N3, N3-tetramethylpropane-1,3-diamine (TSPBA) and polyvinyl alcohol (PVA), and the amino side chain of hyperbranched polylysine (HBPL). Physically enclosed QS inhibitors subsequently exerted the antibacterial effects. This hydrogel can scavenge hydrogen peroxide (H2O2), superoxide anion free radical (·O2 -), hydroxyl radicals (·OH) and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) to reduce oxidative stress and inhibit "bacteria-to-bacteria communication", thus clearing planktonic bacteria and biofilms, accelerating bacterial plasmolysis, reducing bacterial virulence and interfering with membrane transport. After in vivo treatment with hydrogel, nearly all bacteria are eliminated, inflammation is effectively inhibited, and osteogenesis and bone repair are promoted to facilitate recovery from PTO. The work demonstrates the clinical translational potential of the hydrogel in the treatment of drug-resistant bacteria induced PTO.
Asunto(s)
Hidrogeles , Osteomielitis , Percepción de Quorum , Percepción de Quorum/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Animales , Ratones , Modelos Animales de Enfermedad , Antibacterianos/farmacología , Estrés Oxidativo/efectos de los fármacos , Biopelículas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Ratas , MasculinoRESUMEN
The 2D materials exhibit numerous technological applications, but their scalable production is a core challenge. Herein, ball milling exfoliation in supercritical carbon dioxide (scCO2) and polystyrene (PS) is demonstrated to completely exfoliate hexagonal boron nitride nanosheets (BNNSs), graphene, molybdenum disulfide (MoS2), and tungsten disulfide (WS2). The exfoliation yield of 91%, 93%, 92%, and 92% and average aspect ratios of 743, 565, 564, and 502 for BNNSs, graphene, MoS2, and WS2, respectively, are achieved. Integrating exfoliated BNNSS in the polystyrene matrix, 3768 % thermal conductivity in the axial direction and 316% in the cross-plane direction at 12 wt.% loading is increased. Also, the in-plane and cross-plane electrical conductivity of 6.3 × 10-4 S m-1 and 6.6 × 10-3 S m-1, respectively, and the electromagnetic interference (EMI) of 63.3 dB is achieved by exfoliated graphene nanosheets based composite. High thermal and electrical conductivities and EMI shielding are attributed to the high aspect ratio and ultrathin morphology of the exfoliated nanosheets, which exert high charge mobility and form better the percolation network in the composite films due to their high surface area. The process demonstrate herein can produce substantial quantities of diverse 2D nanosheets for widespread commercial utilization.
RESUMEN
Tree peony (Paeonia suffruticosa) is a significant medicinal plant. However, the low rooting number is a bottleneck problem in the micropropagation protocols of P. ostii 'Fengdan'. The activity of superoxide dismutase (SOD) is closely related to root development. But research on the SOD gene's impact on rooting is still lacking. In this study, RNA sequencing (RNA-seq) was used to analyze the four crucial stages of root development in P. ostii 'Fengdan' seedlings, including the early root primordium formation stage (Gmfq), root primordium formation stage (Gmf), root protrusion stage (Gtq), and root outgrowth stage (Gzc). A total of 141.77 GB of data were obtained; 71,718, 29,804, and 24,712 differentially expressed genes (DEGs) were identified in the comparison groups of Gmfq vs. Gmf, Gmf vs. Gtq, and Gtq vs. Gzc, respectively. Among the 20 most highly expressed DEGs in the three comparison groups, only the CuZnSOD gene (SUB13202229, PoSOD) was found to be significantly expressed in Gtq vs. Gzc. The overexpression of PoSOD increased the number of adventitious roots and promoted the activities of peroxidase (POD) and SOD in P. ostii 'Fengdan'. The gene ADVENTITIOUS ROOTING RELATED OXYGENASE1 (PoARRO-1), which is closely associated with the development of adventitious roots, was also significantly upregulated in overexpressing PoSOD plants. Furthermore, PoSOD interacted with PoARRO-1 in yeast two-hybrid (Y2H) and biomolecular luminescence complementation (BiFC) assays. In conclusion, PoSOD could interact with PoARRO-1 and enhance the root development of tube plantlets in P. ostii 'Fengdan'. This study will help us to preliminarily understand the molecular mechanism of adventitious root formation and improve the root quality of tree peony and other medicinal plants.
RESUMEN
As a fungicide with the characteristics of high effectiveness, internal absorption and broad spectrum, imazalil is widely used to prevent and treat in fruits and vegetables. Here, pregnant C57BL/6 mice were exposed to imazalil at dietary levels of 0, 0.025, and 0.25 through drinking water during pregnancy and lactation. We then analyzed the phenotype, metabolome, and expression of related genes and proteins in the livers of mice. There was a marked decrease in the body and liver weights of male offspring mice after maternal imazalil exposure, while this effect on the dam and female offspring was slight. Metabolomics analyses revealed that imazalil significantly altered the metabolite composition of liver samples from both dams and offspring. The preliminary results of the analysis indicated that glucolipid metabolism was the pathway most significantly affected by imazalil. We performed a coabundance association analysis of metabolites with significant changes in the pathway of glycolipid metabolism, and IMZ altered the networks of both dams and offspring compared with the network in control mice, especially in male offspring. The hepatic triglyceride, non-esterified fatty acid and glucose levels were increased significantly in the dams but decreased significantly in male offspring after maternal imazalil exposure. Furthermore, the expression levels of genes associated with glycolipid metabolism and m6A RNA methylation were significantly affected by maternal intake of imazalil. Imazalil-induced glucolipid metabolism disturbance was highly correlated with m6A RNA methylation. In conclusion, maternal imazalil exposure resulted in glucolipid metabolism disturbance and abnormal m6A RNA methylation in the livers of dams and offspring mice. We expected that the information acquired in this study will provide novel evidence for understanding the effect of maternal imazalil exposure on potential health risks.
Asunto(s)
Imidazoles , Hígado , Metilación de ARN , Embarazo , Ratones , Masculino , Femenino , Animales , Ratones Endogámicos C57BL , Hígado/metabolismo , Glucolípidos/metabolismoRESUMEN
Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.
Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/metabolismo , Caspasa 1/metabolismo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Unión Proteica , SumoilaciónRESUMEN
BACKGROUND: Regulatory T cells (Tregs) can alleviate the development of autoimmune and inflammatory diseases, thereby proposing their role as a new therapeutic strategy. Parasitic helminths have co-evolved with hosts to generate immunological privilege and immune tolerance through inducing Tregs. Thus, constructing a "Tregs-induction"-based discovery pipeline from parasitic helminth is a promising strategy to control autoimmune and inflammatory diseases. METHODS: The gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC) were used to isolate immunomodulatory components from the egg extracts of Schistosoma japonicum. The extracted peptides were evaluated for their effects on Tregs suppressive functions using flow cytometry, ELISA and T cell suppression assay. Finally, we carried out colitis and psoriasis models to evaluate the function of Tregs induced by helminth-derived peptide in vivo. FINDINGS: Here, based on target-driven discovery strategy, we successfully identified a small 3 kDa peptide (SjDX5-53) from egg extracts of schistosome, which promoted both human and murine Tregs production. SjDX5-53 presented immunosuppressive function by arresting dendritic cells (DCs) at an immature state and augmenting the proportion and suppressive capacity of Tregs. In mouse models, SjDX5-53 protected mice against autoimmune-related colitis and psoriasis through inducing Tregs and inhibiting inflammatory T-helper (Th) 1 and Th17 responses. INTERPRETATION: SjDX5-53 exhibited the promising therapeutic effects in alleviating the phenotype of immune-related colitis and psoriasis. This study displayed a screening and validation pipeline of the inducer of Tregs from helminth eggs, highlighting the discovery of new biologics inspired by co-evolution of hosts and their parasites. FUNDING: This study was supported by the Natural Science Foundation of China (82272368) and Natural Science Foundation of Jiangsu Province (BK20211586).
Asunto(s)
Enfermedades Autoinmunes , Colitis , Psoriasis , Schistosoma japonicum , Ratones , Humanos , Animales , Linfocitos T Reguladores , Enfermedades Autoinmunes/terapiaRESUMEN
Paeonia ostii is a worldwide ornamental flower and an emerging oil crop. Zyotic embryogenesis is a critical process during seed development, and it can provide a basis for improving the efficiency of somatic embryogenesis (SE). In this study, transcriptome sequencing of embryo development was performed to investigate gene expression profiling in P. ostii and identified Differentially expressed genes (DEGs) related to transcription factors, plant hormones, and antioxidant enzymes. The results indicated that IAA (Indole-3-acetic acid), GA (Gibberellin), BR (Brassinosteroid) and ETH (Ethylene) were beneficial to early embryonic morphogenesis, while CTK (Cytokinin) and ABA (Abscisic Acid) promoted embryo morphogenesis and maturation. The antioxidant enzymes' activity was the highest in early embryos and an important participant in embryo formation. The high expression of the genes encoding fatty acid desaturase was beneficial to fast oil accumulation. Representative DEGs were selected and validated using qRT-PCR. Protein-protein interaction network (PPI) was predicted, and six central node proteins, including AUX1, PIN1, ARF6, LAX3, ABCB19, PIF3, and PIF4, were screened. Our results provided new insights into the formation of embryo development and even somatic embryo development in tree peonies.
Asunto(s)
Paeonia , Transcriptoma , Humanos , Paeonia/genética , Paeonia/metabolismo , Antioxidantes/metabolismo , Perfilación de la Expresión Génica , Desarrollo Embrionario/genética , Regulación de la Expresión Génica de las Plantas , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismoRESUMEN
INTRODUCTION: Epidemiological evidences reveal that populations with psychological stress have an increased likelihood of respiratory viral infection involving influenza A virus (IAV) and SARS-CoV-2. OBJECTIVES: This study aims to explore the potential correlation between psychological stress and increased susceptibility to respiratory viral infections and how this may contribute to a more severe disease progression. METHODS: A chronic restraint stress (CRS) mouse model was used to infect IAV and estimate lung inflammation. Alveolar macrophages (AMs) were observed in the numbers, function and metabolic-epigenetic properties. To confirm the central importance of the gut microbiome in stress-exacerbated viral pneumonia, mice were conducted through microbiome depletion and gut microbiome transplantation. RESULTS: Stress exposure induced a decline in Lactobacillaceae abundance and hence γ-aminobutyric acid (GABA) level in mice. Microbial-derived GABA was released in the peripheral and sensed by AMs via GABAAR, leading to enhanced mitochondrial metabolism and α-ketoglutarate (αKG) generation. The metabolic intermediator in turn served as the cofactor for the epigenetic regulator Tet2 to catalyze DNA hydroxymethylation and promoted the PPARγ-centered gene program underpinning survival, self-renewing, and immunoregulation of AMs. Thus, we uncover an unappreciated GABA/Tet2/PPARγ regulatory circuitry initiated by the gut microbiome to instruct distant immune cells through a metabolic-epigenetic program. Accordingly, reconstitution with GABA-producing probiotics, adoptive transferring of GABA-conditioned AMs, or resumption of pulmonary αKG level remarkably improved AMs homeostasis and alleviated severe pneumonia in stressed mice. CONCLUSION: Together, our study identifies microbiome-derived tonic signaling tuned by psychological stress to imprint resident immune cells and defensive response in the lungs. Further studies are warranted to translate these findings, basically from murine models, into the individuals with psychiatric stress during respiratory viral infection.