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The wild strawberry (Fragaria vesca L.; F. vesca) represents a resilient and extensively studied model organism. While the AP2/ERF gene family plays a pivotal role in plant development, its exploration within F. vesca remains limited. In this study, we characterized the AP2/ERF gene family in wild strawberries using the recently released genomic data (F. vesca V6.0). We conducted an analysis of the gene family expansion pattern, we examined gene expression in stem segments and leaves under cold conditions, and we explored its functional attributes. Our investigation revealed that the FvAP2/ERF family comprises 86 genes distributed among four subfamilies: AP2 (17), RAV (6), ERF (62), and Soloist (1). Tandem and segmental duplications significantly contributed to the growth of this gene family. Furthermore, predictive analysis identified several cis-acting elements in the promoter region associated with meristematic tissue expression, hormone regulation, and resistance modulation. Transcriptomic analysis under cold stress unveiled diverse responses among multiple FvAP2/ERFs in stem segments and leaves. Real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) results confirmed elevated expression levels of select genes following the cold treatment. Additionally, overexpression of FvERF23 in Arabidopsis enhanced cold tolerance, resulting in significantly increased fresh weight and root length compared to the wild-type control. These findings lay the foundation for further exploration into the functional roles of FvAP2/ERF genes.
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Fragaria , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Proteínas de Plantas , Fragaria/genética , Fragaria/metabolismo , Fragaria/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Genoma de Planta , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Respuesta al Choque por Frío/genética , Regiones Promotoras GenéticasRESUMEN
Plants are often exposed to biotic or abiotic stress, which can seriously impede their growth and development. In recent years, researchers have focused especially on the study of plant responses to biotic and abiotic stress. As one of the most widely planted grapevine rootstocks, 'Beta' has been extensively proven to be highly resistant to stress. However, further research is needed to understand the mechanisms of abiotic stress in 'Beta' rootstocks. In this study, we isolated and cloned a novel WRKY transcription factor, VhWRKY44, from the 'Beta' rootstock. Subcellular localization analysis revealed that VhWRKY44 was a nuclear-localized protein. Tissue-specific expression analysis indicated that VhWRKY44 had higher expression levels in grape roots and mature leaves. Further research demonstrated that the expression level of VhWRKY44 in grape roots and mature leaves was highly induced by salt and cold treatment. Compared with the control, Arabidopsis plants overexpressing VhWRKY44 showed stronger resistance to salt and cold stress. The activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were significantly increased, and the contents of proline, malondialdehyde (MDA) and chlorophyll were changed considerably. In addition, significantly higher levels of stress-related genes were detected in the transgenic lines. The results indicated that VhWRKY44 was an important transcription factor in 'Beta' with excellent salt and cold tolerance, providing a new foundation for abiotic stress research.
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Arabidopsis , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Factores de Transcripción , Vitis , Arabidopsis/genética , Arabidopsis/metabolismo , Vitis/genética , Vitis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Estrés Fisiológico/genética , Frío , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Tolerancia a la Sal/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/genéticaRESUMEN
BACKGROUND: N6-methyladenosine (m6A) methylation is a prevalent RNA modification implicated in various diseases. However, its role in intervertebral disc degeneration (IDD), a common cause of low back pain, remains unclear. RESULTS: In this investigation, we explored the involvement of m6A demethylation in the pathogenesis of IDD. Our findings revealed that ALKBH5 (alkylated DNA repair protein AlkB homolog 5), an m6A demethylase, exhibited upregulation in degenerative discs upon mild inflammatory stimulation. ALKBH5 facilitated m6A demethylation within the three prime untranslated region (3'-UTR) of Runx2 mRNA, consequently enhancing its mRNA stability in a YTHDF1 (YTH N6-methyladenosine RNA binding protein F1)-dependent manner. The subsequent elevation in Runx2 expression instigated the upregulation of ADAMTSs and MMPs, pivotal proteases implicated in extracellular matrix (ECM) degradation and IDD progression. In murine models, subcutaneous administration of recombinant Runx2 protein proximal to the lumbar disc in mice elicited complete degradation of intervertebral discs (IVDs). Injection of recombinant MMP1a and ADAMTS10 proteins individually induced mild to moderate degeneration of the IVDs, while co-administration of MMP1a and ADAMTS10 resulted in moderate to severe degeneration. Notably, concurrent injection of the Runx2 inhibitor CADD522 with recombinant Runx2 protein did not result in IVD degeneration in mice. Furthermore, genetic knockout of ALKBH5 and overexpression of YTHDF1 in mice, along with lipopolysaccharide (LPS) treatment to induce inflammation, did not alter the expression of Runx2, MMPs, and ADAMTSs, and no degeneration of the IVDs was observed. CONCLUSION: Our study elucidates the role of ALKBH5-mediated m6A demethylation of Runx2 mRNA in activating MMPs and ADAMTSs, thereby facilitating ECM degradation and promoting the occurrence of IDD. Our findings suggest that targeting the ALKBH5/Runx2/MMPs/ADAMTSs axis may represent a promising therapeutic strategy for preventing IDD.
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Pt2Ca nanoparticles with a mean size diameter of 6 nm can be prepared by heating K2PtCl6, CaH2, carbon black and KCl at 400-500 °C. A mechanism study suggests that the formation of the Pt2Ca phase at moderate temperature is enabled by the fast ion transport via the vacancies in the KCl-CaH2 solid solution. The Pt2Ca nanoparticles exhibit high performance for the oxygen reduction reaction in acid due to optimal adsorption energy of the oxygen intermediate.
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This study investigated the effect of an edible water-extractable arabinoxylan (WEAX) coating on the postharvest preservation of strawberries and cherries. The WEAX film was prepared using carboxymethyl chitosan (CMCS) film as a control, with thorough characterization of its film properties. Subsequently, strawberry and cherry fruits were submerged in a solution containing edible film-forming materials and left to be stored at room temperature, followed by the analysis of their physicochemical parameters to assess their preservation efficacy. The results show that the WEAX film exhibited enhanced flexibility, superior water vapor permeability, thermal stability, and surface morphology. Furthermore, the implementation of WEAX film effectively mitigated weight loss, decay, color degradation, softening process, ascorbic acid decline, anthocyanin accumulation, and an increase in malondialdehyde content in fruits. Thus, the incorporation of WEAX coating demonstrates its capability in prolonging the shelf life of fruits post-harvest, underscoring its potential in fruit preservation practices.
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The NAC (NAM, ATAF1/2, CUC2) family of transcription factors (TFs) is a vital transcription factor family of plants. It controls multiple parts of plant development, tissue formation, and abiotic stress response. We cloned the FvNAC29 gene from Fragaria vesca (a diploid strawberry) for this research. There is a conserved NAM structural domain in the FvNAC29 protein. The highest homology between FvNAC29 and PaNAC1 was found by phylogenetic tree analysis. Subcellular localization revealed that FvNAC29 is localized onto the nucleus. Compared to other tissues, the expression level of FvNAC29 was higher in young leaves and roots. In addition, Arabidopsis plants overexpressing FvNAC29 had higher cold and high-salinity tolerance than the wild type (WT) and unloaded line with empty vector (UL). The proline and chlorophyll contents of transgenic Arabidopsis plants, along with the activities of the antioxidant enzymes like catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) under 200 mM NaCl treatment or -8 °C treatment, were higher than those activities of the control. Meanwhile, malondialdehyde (MDA) and the reactive oxygen species (ROS) content were higher in the WT and UL lines. FvNAC29 improves transgenic plant resistance to cold and salt stress by regulating the expression levels of AtRD29a, AtCCA1, AtP5CS1, and AtSnRK2.4. It also improves the potential to tolerate cold stress by positively regulating the expression levels of AtCBF1, AtCBF4, AtCOR15a, and AtCOR47. These findings suggest that FvNAC29 may be related to the processes and the molecular mechanisms of F. vesca response to high-salinity stress and LT stress, providing a comprehensive understanding of the NAC TFs.
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Arabidopsis , Fragaria , Arabidopsis/genética , Fragaria/genética , Filogenia , Peroxidasas , AntioxidantesRESUMEN
MYB (myoblast) protein comes in large quantities and a wide variety of types and plays a role in most eukaryotes in the form of transcription factors (TFs). One of its important functions is to regulate plant responses to various stresses. However, the role of MYB TFs in regulating stress tolerance in strawberries is not yet well understood. Therefore, in order to investigate the response of MYB family members to abiotic stress in strawberries, a new MYB TF gene was cloned from Fragaria vesca (a diploid strawberry) and named FvMYB108 based on its structural characteristics and evolutionary relationships. After a bioinformatics analysis, it was determined that the gene belongs to the R2R3-MYB subfamily, and its conserved domain, phylogenetic relationships, predicted protein structure and physicochemical properties, subcellular localization, etc. were analyzed. After qPCR analysis of the expression level of FvMYB108 in organs, such as the roots, stems, and leaves of strawberries, it was found that this gene is more easily expressed in young leaves and roots. After multiple stress treatments, it was found that the target gene in young leaves and roots is more sensitive to low temperatures and salt stimulation. After these two stress treatments, various physiological and biochemical indicators related to stress in transgenic Arabidopsis showed corresponding changes, indicating that FvMYB108 may be involved in regulating the plant's ability to cope with cold and high-salt stress. Further research has found that the overexpression of this gene can upregulate the expression of AtCBF1, AtCOR47, AtERD10, and AtDREB1A related to low-temperature stress, as well as AtCCA1, AtRD29a, AtP5CS1, and AtSnRK2.4 related to salt stress, enhancing the ability of overexpressed plants to cope with stress.
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Arabidopsis , Fragaria , Arabidopsis/metabolismo , Tolerancia a la Sal/genética , Fragaria/genética , Fragaria/metabolismo , Filogenia , Genes myb , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
'Beta' is a hybrid of Vitis riparia L. and V. labrusca and has a strong ability to adapt to adverse growth environments and is mainly cultivated and used as a resistant rootstock. At present, the most extensively studied MYB TFs are R2R3-type, which have been found to be involved in plant growth, development, and stress response processes. In the present research, VhMYB15, a key transcription factor for abiotic stress tolerance, was screened by bioinformatics in 'Beta' rootstock, and its function under salinity and drought stresses was investigated. VhMYB15 was highly expressed in roots and mature leave under salinity and drought stresses. Observing the phenotype and calculating the survival rate of plants, it was found that VhMYB15-overexpressing plants exhibited relatively less yellowing and wilting of leaves and a higher survival rate under salinity and drought stresses. Consistent with the above results, through the determination of stress-related physiological indicators and the expression analysis of stress-related genes (AtSOS2, AtSOS3, AtSOS1, AtNHX1, AtSnRK2.6, AtNCED3, AtP5CS1, and AtCAT1), it was found that transgenic Arabidopsis showed better stress tolerance and stronger adaptability under salinity and drought stresses. Based on the above data, it was preliminarily indicated that VhMYB15 may be a key factor in salinity and drought regulation networks, enhancing the adaptability of 'Beta' to adverse environments.
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Arabidopsis , Arabidopsis/metabolismo , Resistencia a la Sequía , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Salinidad , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las Plantas , Sequías , Estrés Fisiológico/genéticaRESUMEN
INTRODUCTION: Osteoarthritis (OA) is a degenerative disease common in the elderly and is characterized by joint pain, swelling, and restricted movement. In recent years, heparanase has been reported to play an important role in the development of osteoarthritic cartilage. PG545 is a heparan sulfate mimetic with heparanase inhibitory activity. In this study, the therapeutic effects and possible mechanisms of PG545 were investigated in a chondrocyte injury model induced by interleukin-1ß (IL -1ß). METHODS: Following treatment with PG545 or the autophagy inhibitor 3-methyladenine (3-MA), chondrocyte viability was detected using Cell Counting Kit-8 and fluorescein diacetate/propidium iodide double staining. The apoptosis rate of chondrocytes was determined by flow cytometry. Expression of light chain 3 and P62 was monitored by immunofluorescence labeling. Western blot, lentivirus infection with red fluorescent protein and green fluorescent protein, and quantitative real-time polymerase chain reaction were used to determine the expression levels of chondrocyte markers, apoptosis-related factors, autophagy proteins, and key proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. The expression and activity of stress-specific enzymes such as malondialdehyde, superoxide dismutase, and catalase (CAT) were investigated. Chondrocytes with ATG5 knockdown were used to investigate the relationship between the therapeutic effect of PG545 and autophagy. The therapeutic effect of PG545 was verified in vivo. RESULTS: PG545 had a significant protective effect on chondrocytes by reducing oxidative stress, apoptosis, and degradation of chondrocytes and increasing chondrocyte proliferation. PG545 was effective in inducing autophagy in IL-1ß-treated cells, while 3-MA attenuated the effect. The PI3K/Akt/mTOR pathway may be involved in the promotion of autophagy and OA treatment by PG545. CONCLUSION: PG545 was able to restore impaired autophagy and autophagic flux via the PI3K/Akt/mTOR pathway, thereby delaying the progression of OA, suggesting that PG545 may be a novel therapeutic approach for OA.
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Osteoartritis , Proteínas Proto-Oncogénicas c-akt , Humanos , Anciano , Proteínas Proto-Oncogénicas c-akt/metabolismo , Condrocitos , Fosfatidilinositol 3-Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/prevención & control , Osteoartritis/metabolismo , Fosfatidilinositol 3-Quinasa , Inhibidores de la Angiogénesis/farmacología , Autofagia , ApoptosisRESUMEN
PURPOSE: In the context of the current comfort medicine and enhanced recovery after surgery, there is a demand for a new anesthesia method to reduce adverse reactions and accelerate recovery after surgery. This randomized controlled trial aimed to compare the efficacy and safety between opioid-free anesthesia (OFA) combined with ultrasound-guided intermediate cervical plexus block (ICPB) and opioid-based anesthesia in patients after thyroid surgery. METHODS: In this study, 75 patients scheduled for thyroid surgery under general anesthesia were randomly allocated into two groups. The primary outcome included the incidence of nausea within 24 h after surgery. The main secondary outcomes included the incidence of vomiting and the visual analog score (VAS) scores within 24 h after surgery as well as the quality of recovery 40 questionnaires (QoR-40) scores 24 h after surgery. RESULTS: In the OFA group, the incidence of postoperative nausea was 6.1%, compared to 39.4% in the control group (p = 0.001). No patient presented with postoperative vomiting in the OFA group, while 15.2% of patients suffered from postoperative vomiting in the control group (p = 0.063). The VAS scores of patients in the postanesthetic care unit (PACU) and 2 h, 4 h, and 6 h after surgery were lower in the OFA group, and the difference is statistically significant. Besides, the VAS scores of patients at rest (p = 1.000) and during swallowing (p = 1.000) 24 h after surgery were comparable. CONCLUSION: Compared with opioid-based anesthesia, the OFA combined with the ultrasound-guided ICPB can better improve patients' postoperative recovery, reduce nausea, and decrease pain scores. TRIAL REGISTRATION: Chinese Clinical Trial Regisrty, ChiCTR2200056344, https://www.chictr.org.cn.
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Analgésicos Opioides , Bloqueo del Plexo Cervical , Humanos , Analgésicos Opioides/uso terapéutico , Bloqueo del Plexo Cervical/efectos adversos , Bloqueo del Plexo Cervical/métodos , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/epidemiología , Glándula Tiroides/cirugía , Anestesia General/métodos , Ultrasonografía Intervencional/métodosRESUMEN
ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be a tumor suppressor. Recently, loss-of-function of ARID1A gene has been shown to cause intellectual disability. Here we generate Arid1a conditional knockout mice and investigate Arid1a function in the hippocampus. Disruption of Arid1a in mouse forebrain significantly decreases neural stem/progenitor cells (NSPCs) proliferation and differentiation to neurons within the dentate gyrus (DG), increasing perinatal and postnatal apoptosis, leading to reduced hippocampus size. Moreover, we perform single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and reveal that Arid1a is necessary for the maintenance of the DG progenitor pool and survival of post-mitotic neurons. Transcriptome and ChIP-seq analysis data demonstrate that ARID1A specifically regulates Prox1 by altering the levels of histone modifications. Overexpression of downstream target Prox1 can rescue proliferation and differentiation defects of NSPCs caused by Arid1a deletion. Overall, our results demonstrate a critical role for Arid1a in the development of the hippocampus and may also provide insight into the genetic basis of intellectual disabilities such as Coffin-Siris syndrome, which is caused by germ-line mutations or microduplication of Arid1a.
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Anomalías Múltiples , Neoplasias , Animales , Femenino , Ratones , Embarazo , Anomalías Múltiples/genética , Cromatina , Ensamble y Desensamble de Cromatina , Giro Dentado , Proteínas Nucleares/metabolismoRESUMEN
Arabinoxylan (AX) is a dietary fiber that has been proven to have a significant antidiabetic effect. Liver metabolic disorders frequently coincide with the development of type 2 diabetes, but research on the hepatoprotective effects of AX in type 2 diabetic mice is lacking. As AX is abundant in the wastewater produced during vital wheat gluten protein production, this study used it as a raw material to evaluate its protective effect on liver function. The study employed an AX intervention in type 2 diabetic mice induced by a high-fat diet combined with streptozotocin and collected serum and liver tissue samples after 4 weeks. Serum and liver function indicators were measured using an automatic biochemistry analysis apparatus, and liver fat accumulation was observed using oil red O staining. Nontargeted metabolomics analysis of liver tissues was conducted using UHPLC-MS/MS. The results showed that AX significantly improved liver function indicators and histopathological damage, and regulated liver metabolic disorders by improving the differential metabolites of pantothenate and CoA biosynthesis, as well as purine metabolism. This study demonstrated that AX may exert a significant hepatoprotective effect by regulating metabolic disorders.
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Internet healthcare is a crucial component of the healthcare industry's digital transformation and plays a vital role in achieving China's Healthy China strategy and promoting universal health. To ensure the development of internet healthcare is guided by scientifically sound policies, this study analyzes and assesses current policy texts, aiming to identify potential issues and inadequacies. By examining 134 national-level policy documents, utilizing multiple research methods, including policy bibliometrics, content analysis, and the PMC Index Model, the study investigates policy characteristics, distribution of policy instruments, and evaluation outcomes related to internet healthcare. The study findings reveal that internet healthcare policies place emphasis on enhancing service quality, driving technological innovation, and promoting management standardization. Although policy instruments align with the current stage of internet healthcare development in China, they are plagued by imbalances in implementation. While policies are generally well-formulated, there are discernible discrepancies among them, necessitating the reinforcement and refinement of certain provisions. Hence, it is imperative to strategically optimize the amalgamation and implementation of policy instruments while concurrently endeavoring to achieve a dynamic equilibrium in policy combinations. Furthermore, policymakers should diligently refine the policy content pertaining to its nature and effectiveness in order to fully maximize policy utility.
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In viticulture, the highly resistant rootstock 'Beta' is widely used in Chinese grape production to avoid the effects of soil salinization and drought on grape growth. However, the mechanism of high resistance to abiotic stress in the 'Beta' rootstock is not clear. In this study, we demonstrated that VhMYB2 as a transcription factor made a significant contribution to salinity and drought stress, which was isolated from the 'Beta' rootstock. The coding sequence of the VhMYB2 gene was 858 bp, encoding 285 amino acids. The subcellular localization of VhMYB2 was located in the nucleus of tobacco epidermal cells. Moreover, RT-qPCR found that VhMYB2 was predominantly expressed in the mature leaf and root of the grape. Under salinity and drought stress, overexpressing VhMYB2 showed a higher resistant phenotype and survival rates in A. thaliana while the transgenic lines had a survival advantage by measuring the contents of proline, chlorophyll, and MDA, and activities of POD, SOD, and CAT, and expression levels of related stress response genes. The results reveal that VhMYB2 may be an important transcription factor regulating 'Beta' resistance in response to abiotic stress.
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Arabidopsis , Vitis , Arabidopsis/metabolismo , Resistencia a la Sequía , Vitis/genética , Vitis/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Salinidad , Estrés Fisiológico/genética , Sequías , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: Intervertebral disc degeneration (IDD) naturally occurs during the aging process. Its occurrence is closely related to chronic inflammation; however, the causal relationship between them is controversial. This study aimed to investigate if inflammation would promote IDD incidence and explore the underlying mechanism. METHODS: A chronic inflammation mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Enzyme-linked immunosorbent assay was performed to determine proinflammatory cytokines in serum. Histological staining was used to evaluate the degeneration of IVDs. Immunoblots and RT-qPCR analyses were performed to measure protein and mRNA expression levels. Immunoprecipitation, mass spectrometry, and co-immunoprecipitation assays were used to determine the assembly of protein complex. RESULTS: We found that an inflammatory microenvironment activated p38 kinase, which phosphorylated the Runx2 transcription factor at the Ser28 site. The phosphorylated Runx2 (pRunx2) then recruited a deubiquitinase, ubiquitin-specific peptidase 24 (USP24), which stabilized pRunx2 and protected it from ubiquitin-dependent proteasomal degradation. The stabilized pRunx2 recruited histone acetyltransferase p300 and nuclear receptor coactivator 3 (NCOA3) to assemble a complex. This NCOA3-p300-pRunx2 complex then transactivated the expression of 13 ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) genes, thereby promoting the degradation of extracellular matrix (ECM) in intervertebral discs (IVDs) and causing IDD. Administration of either a p38 inhibitor (doramapimod), a NCOA3 inhibitor (bufalin), or a p300 inhibitor (EML425) significantly decreased the expression of the 13 ADAMTS genes and slowed the degeneration of IVDs. CONCLUSION: In summary, our results demonstrate that USP24 protects pRunx2 from proteasomal degradation under chronic inflammation conditions, enabling pRunx2 to transactivate ADAMTS genes and degrade ECM. Our findings provide direct evidence that chronic inflammation triggers IDD and offer a therapeutic strategy for retarding IDD in patients with chronic inflammation.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Ratones , Animales , Coactivador 3 de Receptor Nuclear/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Inflamación/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismoRESUMEN
BACKGROUND: There are no studies that have shown the role and underlying mechanism of Polyphyllin I (PPI)-mediated anti-apoptosis activity in nucleus pulposus cells (NPCs). The research aimed to evaluate the effects of PPI in interleukin (IL)-1ß-induced NPCs apoptosis in vitro. METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability, and cell apoptosis was evaluated by double-stained flow cytometry (FITC Annexin V/PI). The expression of miR-503-5p was quantified by real-time quantitative PCR (qRT-PCR), and the expression of Bcl-2, Bax, and cleaved caspase-3 was quantified by Western blot. Dual-luciferase reporter gene assay was used to detect the targeting relationship between miR-503-5p and Bcl-2. RESULTS: PPI at 40 µg·mL-1 markedly promoted the viability of NPCs (P < 0.01). Also, PPI inhibited apoptosis and reduction in proliferative activity induced by IL-1ß in the NPCs (P < 0.001, 0.01). PPI treatment significantly inhibited the expression of apoptosis-related protein Bax, cleaved caspase-3 (P < 0.05, 0.01), and enhanced the level of anti-apoptotic protein Bcl-2 (P < 0.01). The proliferative activity of NPCs was significantly decreased and the apoptosis rate of NPCs was increased under IL-1ß treatment (P < 0.01, 0.001). Moreover, miR-503-5p was highly expressed in IL-1ß-induced NPCs (P < 0.001). Furthermore, the effect of PPI on NPCs viability and apoptosis in IL-1ß treatment was dramatically reversed by the overexpression of miR-503-5p (P < 0.01, 0.01). The targeted binding of miR-503-5p to the 3'UTR of Bcl-2 mRNA was confirmed by dual-luciferase reporter gene assays (P < 0.05). In further experiments, compared with miR-503-5p mimics, the effects of PPI on IL-1ß-induced NPCs viability and apoptosis were greatly reversed by the co-overexpression of miR-503-5p and Bcl-2 (P < 0.05, 0.05). CONCLUSION: PPI suppressed the apoptosis of intervertebral disk (IVD) NPCs induced by IL-1ß via miR-503-5p/Bcl-2 molecular axis.
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MicroARNs , Núcleo Pulposo , Caspasa 3 , Proteína X Asociada a bcl-2 , MicroARNs/genéticaRESUMEN
Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologically active compounds in immuno-oncology may open new avenues for more effective cancer therapies. In this review, we explore how natural compounds modulate the epigenetic machinery to shape antitumor immune response, highlighting the promise offered by the Mother Nature that could be exploited therapeutically to improve outcomes for cancer patients.
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Epigénesis Genética , Neoplasias , Humanos , Inmunoterapia , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Microambiente TumoralRESUMEN
Iron is involved in various metabolic pathways of plants. Stress from iron deficiency and toxicity in the soil adversely affects plant growth. Therefore, studying the mechanism of iron absorption and transport by plants is of important for resistance to iron stress and to increase crop yield. In this study, Malus xiaojinensis (a Fe-efficient Malus plant) was used as research material. A ferric reduction oxidase (FRO) family gene member was cloned and named MxFRO4. The MxFRO4 encoded a protein of 697 amino acid residues with a predicted molecular weight of 78.54 kDa and a theoretical isoelectric point of 4.90. A subcellular localization assay showed that the MxFRO4 protein was localized on the cell membrane. The expression of MxFRO4 was enriched in immature leaves and roots of M. xiaojinensis, and was strongly affected by low-iron, high-iron, and salt treatments. After introduction of MxFRO4 into Arabidopsis thaliana, the iron and salt stress tolerance of transgenic A. thaliana was greatly improved. Under exposure to low-iron and high-iron stresses, the primary root length, seedling fresh weight, contents of proline, chlorophyll, and iron, and iron(III) chelation activity of the transgenic lines were significantly increased compared with the wild type. The contents of chlorophyll and proline, and the activities of the antioxidant enzymes superoxide dismutase, peroxidase, and catalase were significantly higher in transgenic A. thaliana overexpressing MxFRO4 under salt stress compared with the wild type, whereas the malondialdehyde content was decreased. These results suggest that MxFRO4 contributes to alleviating the effects of low-iron, high-iron, and salinity stresses in transgenic A. thaliana.
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Antioxidantes , Arabidopsis , Antioxidantes/metabolismo , Arabidopsis/metabolismo , Hierro/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Tolerancia a la Sal/genética , Prolina/metabolismo , Clorofila/metabolismo , Estrés Fisiológico , Regulación de la Expresión Génica de las PlantasRESUMEN
Heat Shock Factor 1 (HSF1) is a master regulator of heat shock responsive signaling. In addition to playing critical roles in cellular heat shock response, emerging evidence suggests that HSF1 also regulates a non-heat shock responsive transcriptional network to handle metabolic, chemical, and genetic stress. The function of HSF1 in cellular transformation and cancer development has been extensively studied in recent years. Due to important roles for HSF1 for coping with various stressful cellular states, research on HSF1 has been very active. New functions and molecular mechanisms underlying these functions have been continuously discovered, providing new targets for novel cancer treatment strategies. In this article, we review the essential roles and mechanisms of HSF1 action in cancer cells, focusing more on recently discovered functions and their underlying mechanisms to reflect the new advances in cancer biology. In addition, we emphasize new advances with regard to HSF1 inhibitors for cancer drug development.
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Neoplasias , Factores de Transcripción , Humanos , Factores de Transcripción/metabolismo , Factores de Transcripción del Choque Térmico/genética , Factores de Transcripción del Choque Térmico/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Transformación Celular Neoplásica , Respuesta al Choque TérmicoRESUMEN
Methanol steam reforming (MSR) and hydrolysis of metal hydrides are two important hydrogen generation reactions with complementary characteristics. Coupling of the above two reactions leads to better hydrogen generation performance. The CO2 generated from MSR can be absorbed by the hydroxide generated from hydrolysis, leading to higher H2 purity. The hydrolysis heat can be utilized to drive the endothermic MSR reaction. By carrying out MSR on a CaH2-CuO composite, a hydrogen density of 6.56 wt% based on all the reactants with H2 purity higher than 99% can be obtained at 250 °C.