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Liver fibrosis/cirrhosis is a pathological state caused by excessive extracellular matrix deposition. Sustained activation of hepatic stellate cells (HSC) is the predominant cause of liver fibrosis, but the detailed mechanism is far from clear. In this study, we found that long noncoding RNA Fendrr is exclusively increased in hepatocytes in the murine model of CCl4- and bile duct ligation-induced liver fibrosis, as well as in the biopsies of liver cirrhosis patients. In vivo, ectopic expression of Fendrr aggravated the severity of CCl4-induced liver fibrosis in mice. In contrast, inhibiting Fendrr blockaded the activation of HSC and ameliorated CCl4-induced liver fibrosis. Our mechanistic study showed that Fendrr binds to STAT2 and enhances its enrichment in the nucleus, which then promote the expression of interleukin 6 (IL-6), and, ultimately, activates HSC in a paracrine manner. Accordingly, disrupting the interaction between Fendrr and STAT2 by ectopic expression of a STAT2 mutant attenuated the profibrotic response inspired by Fendrr in the CCl4-induced liver fibrosis. Notably, the increase of Fendrr in patient fibrotic liver is positively correlated with the severity of fibrosis and the expression of IL-6. Meanwhile, hepatic IL-6 positively correlates with the extent of liver fibrosis and HSC activation as well, thus suggesting a causative role of Fendrr in HSC activation and liver fibrosis. In conclusion, these observations identify an important regulatory cross talk between hepatocyte Fendrr and HSC activation in the progression of liver fibrosis, which might represent a potential strategy for therapeutic intervention.
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Hepatócitos , Interleucina-6 , Cirrose Hepática , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Tetracloreto de Carbono/toxicidade , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Interleucina-6/metabolismo , Interleucina-6/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/patologia , Camundongos Endogâmicos C57BL , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT2/metabolismo , Fator de Transcrição STAT2/genéticaRESUMO
MicroRNAs (miRNAs) are small noncoding RNAs that play a vital role in plant responses to abiotic and biotic stresses. Recently, it has been discovered that some primary miRNAs (pri-miRNAs) encode regulatory short peptides called miPEPs. However, the presence of miPEPs in rice, and their functions in response to abiotic stresses, particularly stress induced by heavy metals, remain poorly understood. Here, we identified a functional small peptide (miPEP156e) encoded by pri-miR156e that regulates the expression of miR156 and its target SPL genes, thereby affecting miR156-mediated cadmium (Cd) tolerance in rice. Overexpression of miPEP156e led to decreased uptake and accumulation of Cd and reactive oxygen species (ROS) levels in plants under Cd stress, resulting in improved rice Cd tolerance, as observed in miR156-overexpressing lines. Conversely, miPEP156e mutants displayed sensitivity to Cd stress due to the elevated accumulation of Cd and ROS. Transcriptome analysis further revealed that miPEP156e improved rice Cd tolerance by modulating Cd transporter genes and ROS scavenging genes. Our study provides insights into the regulatory mechanism of miPEP156e in rice response to Cd stress and demonstrates the potential of miPEPs as an effective tool for improving crop abiotic stress tolerance.
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MicroRNAs , Oryza , MicroRNAs/genética , MicroRNAs/metabolismo , Cádmio/metabolismo , Oryza/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Peptídeos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Circulating tumor DNA (ctDNA) is a highly promising biomarker for the early diagnosis and treatment of gastric cancer (GC). However, there is still a lack of effective and practical ctDNA detection methods. In this work, a simple and economical capillary non-gel sieving electrophoresis-LED induced fluorescence detection (NGCE-LEDIF) platform coupled with catalytic hairpin assembly (CHA) as the signal amplification strategy is proposed for quantitative detection of PIK3CA E542K and TP53 (two types of ctDNA associated with GC). We have reasonably designed two pairs of programmable oligonucleotide hairpin probes for PIK3CA E542K and TP53. Using a one-pot reaction, the presence of ctDNA triggers the cyclic amplification of CHA, forming numerous thermodynamically stable H1/H2 double-strands. The H1/H2 double-stranded DNA catalyzed by PIK3CA E542K and TP53 can be easily separated by NGCE due to their different lengths, enabling simultaneous detection of both ctDNAs. Under optimal experimental conditions, the detection limits of this strategy for detecting GC-related biomarkers PIK3CA E542K and TP53 are 20.35 pM and 19.61 pM, respectively, and can achieve 730-fold signal amplification. This strategy has a good recovery in the serum matrix. The results of this study show that this strategy has significant advantages such as high selectivity, a simple process, no special instruments and equipment, no need for fluorescence modification of hairpin probes in advance, high automation, low cost, and minimal sample consumption. This provides a powerful method for the detection of trace cancer biomarkers in the serum matrix with good application prospects.
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Técnicas Biossensoriais , DNA Tumoral Circulante , DNA Catalítico , DNA Tumoral Circulante/genética , DNA/genética , Espectrometria de Fluorescência/métodos , Eletroforese Capilar , Classe I de Fosfatidilinositol 3-Quinases/genética , Técnicas Biossensoriais/métodos , Limite de DetecçãoRESUMO
The electrosynthesis of hydrogen peroxide (H2O2) offers a sustainable and viable option for generating H2O2 directly, as an alternative to the anthraquinone oxidation method. This study focuses on the comparative study of Co nanoparticles and single-atomic Co sites (Co SACs) that were encapsulated into nitrogen-doped carbon for the electrosynthesis of H2O2, which has been synthesized by direct pyrolysis of Zn/Co-ZIF or Co-based zeolitic imidazolate frameworks (ZIF-67). The electrochemical measurement results demonstrate that the coexistence of Co nanoparticles and single-atomic Co sites in the CoNC catalyst is more conducive for H2O2 production compared to Co SACs only, possessing better H2O2 selectivity of 73.3% and higher faradaic efficiency of 87%. The improved performance of CoNC with SACs can be attributed to the presence of additional Co nanoparticles in the nitrogen-doped carbon layers.
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KEY MESSAGE: CmMYB308 was identified as a key regulator in chrysanthemum flower color variation from purple to pink by conducting transcriptome and metabolome analysis. CmMYB308 can inhibit anthocyanin biosynthesis by suppressing the expression of CmPAL, CmC4H, and Cm4CL. Flower color variation is a widespread natural occurrence that plays a significant role in floral breeding. We discovered a variation in the flower of the chrysanthemum cultivar 'Dante Purple' (abbreviated as 'DP'), where the flower color shifted from purple to pink. We successfully propagated these pink flowers through tissue culture and designated them as DPM. By conducting transcriptome and metabolome analysis, we identified a reduction in the expression of critical genes involved in anthocyanin biosynthesis-CmPAL, CmC4H, and Cm4CL-in the DPM. This downregulation led to an accumulation of phenylalanine and cinnamic acid within the general phenylpropanoid pathway (GPP), which prevented their conversion into cyanidin and cyanidin 3-glucoside. As a result, the flowers turned pink. Additional transformation and biochemical experiments confirmed that the upregulation of CmMYB308 gene expression in the DPM directly suppressed CmPAL-1 and CmC4H genes, which indirectly affected Cm4CL-3 expression and ultimately inhibited anthocyanin biosynthesis in the DPM. This study offers a preliminary insight into the molecular mechanism underlying chrysanthemum flower color mutation, paving the way for genetic improvements in chrysanthemum flower color breeding.
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Antocianinas , Chrysanthemum , Flores , Regulação da Expressão Gênica de Plantas , Pigmentação , Proteínas de Plantas , Chrysanthemum/genética , Chrysanthemum/metabolismo , Flores/genética , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Antocianinas/metabolismo , Pigmentação/genética , Transcriptoma/genética , Metabolômica/métodos , Metaboloma/genética , Perfilação da Expressão Gênica , Cor , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Cyclic N-sulfonyl aldimines are well-known aza-[2C]-synthons for various [2 + n] annulation reactions. Herein we describe a novel base mediated [2 + 1] annulation and a regioselective aziridine ring-opening reaction cascade, which provides an efficient and distinct synthetic strategy from readily available cyclic N-sulfonyl aldimines and α-carbonyl sulfonium salts leading to ß-amino ketone derivatives through the corresponding fused tri-substituted aziridines. This one-pot, two-step process involves formation of C-C and C-N bonds and subsequent cleavage of a C-N bond. The features of the developed reaction include the use of mild reaction conditions, broad substrate scope, and excellent yields. The synthetic utility of this approach was demonstrated by gram-scale operation and further product derivatizations.
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Background: Mobile phone addiction has adverse influences on the physical and mental health of college students. However, few studies shed light on the effect of fear of missing out on mobile phone addiction and the underlying mechanisms among college students. Methods: To explore their associations, the present study used the Fear of Missing Out Scales (FoMOS), Loneliness Scale (USL-8), Mobile Phone Addiction Index Scale (MPAI), and Depression-Anxiety-Stress Questionnaire (DASS-21) to investigate 750 college students. Results: The results suggested that fear of missing out significantly positively predicted mobile phone addiction. This direct effect could be mediated by depression, and the indirect effect of fear of missing out on mobile phone addiction could be moderated by loneliness. Specifically, the indirect effect was stronger for students with high levels of loneliness. Conclusion: This study provides a theoretical basis for developing future interventions for mobile phone addiction in higher education students.
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Depressão , Solidão , Humanos , Medo , Estudantes , Dependência de TecnologiaRESUMO
ABSTRACT: Cerebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture. Patients with cerebral palsy are often only capable of limited activity, resulting from non-progressive disturbances in the fetal or neonatal brain. These disturbances severely impact the child's daily life and impose a substantial economic burden on the family. Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes, the understanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity. This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development. It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development, which can be further influenced by environmental factors. Despite continuous research endeavors, the underlying factors contributing to cerebral palsy remain are still elusive. However, significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development. Moreover, these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping, including thrombosis, angiogenesis, mitochondrial and oxidative phosphorylation function, neuronal migration, and cellular autophagy. Furthermore, exploring targeted genotypes holds potential for precision treatment. In conclusion, advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy. These breakthroughs have the potential to pave the way for new treatments and therapies, consequently shaping the future of cerebral palsy research and its clinical management. The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies. By elucidating the underlying cellular mechanisms, we can develop targeted interventions to optimize outcomes. A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.
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Aluminum toxicity poses a significant constraint on crop production in acidic soils. While phytohormones are recognized for their pivotal role in mediating plant responses to aluminum stress, the specific involvement of gibberellin (GA) in regulating aluminum tolerance remains unexplored. In this study, we demonstrate that external GA exacerbates the inhibitory impact of aluminum stress on root growth of rice seedlings, concurrently promoting reactive oxygen species (ROS) accumulation. Furthermore, rice plants overexpressing the GA synthesis gene SD1 exhibit enhanced sensitivity to aluminum stress. In contrast, the slr1 gain-of-function mutant, characterized by impeded GA signaling, displays enhanced tolerance to aluminum stress, suggesting the negative regulatory role of GA in rice resistance to aluminum-induced toxicity. We also reveal that GA application suppresses the expression of crucial aluminum tolerance genes in rice, including Al resistance transcription factor 1 (ART1), Nramp aluminum transporter 1 (OsNramp4), and Sensitive to Aluminum 1 (SAL1). Conversely, the slr1 mutant exhibits up-regulated expression of these genes compared to the wild type. In summary, our results shed light on the inhibitory effect of GA in rice resistance to aluminum stress, contributing to a theoretical foundation for unraveling the intricate mechanisms of plant hormones in regulating aluminum tolerance.
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OBJECTIVE: We created a novel, high sensitivity immunochromatographic assay that allows for clear and precise quantitative analysis by employing innovative bimetallic nanoparticles with peroxide-like activity as markers for the preparation of the test strip. METHODS: Initially, we synthesized Pt-Pd bimetallic nanoparticles through the reduction of K2PtCl4 and Na2PdCl4 using ascorbic acid (AA) in an ultrasonic water bath. These bimetallic nanoparticles were then utilized to label purified antigens from the foot-and-mouth disease virus (FMDV) type O (FMDV-146S), resulting in the creation of antigen-captured nanomarkers. Upon completion of the antigen-antibody reaction, we introduced a color-developing agent (3,3',5,5'-tetramethylbenzidine) for cascade amplification, significantly enhancing detection sensitivity while ensuring clear and accurate quantitative analysis. RESULTS: The quantitative detection sensitivity achieved was 1:28/test, with a linear range spanning from 1:26 â¼ 1:29 /test. For FMDV type O positive serum, the detection sensitivity reached 96.7 %. Furthermore, this method exhibited a 95 % detection sensitivity for FMDV negative serum, FMDV type A and type Asiaâ positive sera, as well as sera positive for other common viral diseases in animals. In comparison to the OIE-recommended LPB-ELISA, this approach displayed higher correlation (correlation coefficient = 0.909). Innovation was at the core of establishing this immunochromatographic assay based on Pt-Pd bimetallic nanoparticles for the detection of FMDV antibodies. CONCLUSION: The findings revealed a striking 24-fold improvement in sensitivity when compared to colloidal gold, accompanied by a strong correlation coefficient (R2 > 0.9). This suggests a robust and consistent linear association in the results. This method represents a significant advancement in the field of rapid immunochromatographic assays, offering a promising alternative application for bimetallic nanoparticles.
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Vírus da Febre Aftosa , Febre Aftosa , Animais , Febre Aftosa/diagnóstico , Sorogrupo , Imunoensaio/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Sensibilidade e EspecificidadeRESUMO
As the incidence of precocious puberty has risen in recent years and the age at puberty onset is younger, children may be at increased risk for health consequences associated with the early onset of puberty. Bisphenol A (BPA) is recognized as an endocrine disruptor chemical that is reported to induce precocious puberty. The effect of BPA exposure modes, times, and doses (especially low dose) were controversial. In the present study, we evaluated the potential effects of maternal exposure to low-dose BPA on the hypothalamus, particularly on the arcuate (ARC) nucleus and anteroventral periventricular (AVPV) nucleus during peri-puberty in offspring of BPA-treated rats. Pregnant rats were exposed to corn oil vehicle, 0.05 mg·kg-1·day-1 BPA, or 5 mg·kg-1·day-1 from gestation day 1 (GD1) to postnatal day 21 (PND21) by daily gavage. Body weight (BW), vaginal opening (VO), ovarian follicular luteinization, and relevant hormone concentrations were measured; hypothalamic Kiss1 and GnRH1 levels by western immunoblot analysis were also assessed as indices of puberty onset. During or after exposure, low-dose BPA restricted BW after birth (at PND1 and PND5), and subsequently accelerated puberty onset by promoting the expression of prepubertal Kiss1 and GnRH1 in the AVPV nucleus on PND30, leading to advanced VO, an elevation in LH and FSH concentrations (on PND30). We also noted increased BW on PND30 and PND35. Maternal oral exposure to low-dose BPA altered the BW curve during the neonatal and peripubertal periods, and subsequently accelerated puberty onset by promoting prepubertal Kiss1 expression in the AVPV nucleus.
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Compostos Benzidrílicos , Exposição Materna , Fenóis , Puberdade Precoce , Gravidez , Criança , Ratos , Feminino , Animais , Humanos , Kisspeptinas/metabolismo , PuberdadeRESUMO
AIMS: Neuropathic pain is a common chronic pain disorder, which is largely attributed to spinal central sensitization. Calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) activation in the spinal dorsal horn (SDH) is a major contributor to spinal sensitization. However, the exact way that CaMKIIα-positive (CaMKIIα+) neurons in the SDH induce neuropathic pain is still unclear. This study aimed to explore the role of spinal CaMKIIα+ neurons in neuropathic pain caused by chronic constriction injury (CCI) and investigate the potential epigenetic mechanisms involved in CaMKIIα+ neuron activation. METHODS: CCI-induced neuropathic pain mice model, Sirt1loxP/loxP mice, and chemogenetic virus were used to investigate whether the activation of spinal CaMKIIα+ neurons is involved in neuropathic pain and its involved mechanism. Transcriptome sequence, western blotting, qRT-PCR, and immunofluorescence analysis were performed to assay the expression of related molecules and activation of neurons. Co-immunoprecipitation was used to observe the binding relationship of protein. Chromatin immunoprecipitation (ChIP)-PCR was applied to analyze the acetylation of histone H3 in the Scn3a promoter region. RESULTS: The expression of sodium channel Nav1.3 was increased and the expression of SIRT1 was decreased in the spinal CaMKIIα+ neurons of CCI mice. CaMKIIα neurons became overactive after CCI, and inhibiting their activation relieved CCI-induced pain. Overexpression of SIRT1 reversed the increase of Nav1.3 and alleviated pain, while knockdown of SIRT1 or overexpression of Nav1.3 promoted CaMKIIα+ neuron activation and induced pain. By knocking down spinal SIRT1, the acetylation of histone H3 in the Scn3a (encoding Nav1.3) promoter region was increased, leading to an increased expression of Nav1.3. CONCLUSION: The findings suggest that an aberrant reduction of spinal SIRT1 after nerve injury epigenetically increases Nav1.3, subsequently activating CaMKIIα+ neurons and causing neuropathic pain.
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Neuralgia , Neurônios , Sirtuína 1 , Animais , Masculino , Camundongos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Camundongos Endogâmicos C57BL , Neuralgia/metabolismo , Neurônios/metabolismo , Sirtuína 1/metabolismo , Sirtuína 1/genética , Medula Espinal/metabolismoRESUMO
A facile and efficient strategy for modular access to furo[3,2-c]chromen-4-ones using 4-hydroxycoumarin and ß-nitroalkenes via Lewis acid-catalyzed formal [3 + 2] annulation protocol is described. This reaction proceeds via cascade Michael addition/nucleophilic addition/elimination in the presence of Yb(OTf)3, which involves the formation of two new σ (C-C and C-O) bonds for the construction of a novel furan ring in a single operation. This protocol affords a variety of functional groups, thereby providing a practical and efficient method for the fabrication of a furo[3,2-c]chromen-4-one framework.
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Three iridium(III) complexes were designed with the purpose of elucidating the photo-physicochemical properties of iridium(III) complexes with narrow band gap at the electronic level. This study indicates that increasing the ligand rigidity and electron delocalization of the compounds can suppress the ring-stretching vibrations of the iridium(III) complex, thus improving their photo-chemical activity and photocytotoxicity.
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Enterococcus faecium (E. faecium) and Bacillus subtilis (B. subtilis) are widely used as probiotics to improve performance in animal production, but there have been few reports of their impacts on pigeon milk. In this study, twenty-four pairs of parental pigeons were randomly divided into four groups, with six replicates, and each pair feeding three squabs. The control group drank normal water. The E. faecium group, B. subtilis group, and mixed group drank water supplemented with 3 × 106 CFU/mL E. faecium, 2 × 107 CFU/mL B. subtilis, and a mixture of these two probiotics, respectively. The experiment lasted 19 days. The results demonstrated that the IgA and IgG levels were significantly higher in the milk of Group D pigeons than in the other groups. At the phylum level, Fimicutes, Actinobacteria, and Bacteroidetes were the three main phyla identified. At the genus level, Lactobacillus, Bifidobacterium, Veillonella, and Enterococcus were the four main genera identified. In conclusion, drinking water supplemented with E. faecium and B. subtilis could improve immunoglobulin levels in pigeon milk, and this could increase the ability of squabs to resist disease. E. faecium and B. subtilis could be used as probiotics in the pigeon industry.
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Background: Precocious puberty (PP) involves early activation of the hypothalamic gonadotropin-releasing hormone (GnRH) generator. The RFamide-related peptide/G protein-coupled receptor 147 (RFRP3/GPR147) signaling pathway is vital in inhibiting GnRH and delaying puberty onset. The nourishing Yin-removing fire (NYRF) herbal mixture has shown promising results in treating PP. Objective: This study aimed to assess the impact of the NYRF herbal mixture on the RFRP3/GPR147 signaling pathway in the hypothalamus and its potential in alleviating PP in female rats. Materials and Methods: In a controlled experiment, 24 female Sprague-Dawley rats (11.20 ± 0.69 gr, postnatal day [PD5]) were divided into normal, model, normal saline, and NYRF groups (n = 6/each). PP was induced in the model, normal saline, and NYRF groups by subcutaneous injection of danazol at PD5. The NYRF herbal mixture or normal saline was administered from PD15. Serum sex hormone levels and hypothalamic samples were collected for mRNA and protein expression at PD30. Results: In the model group, hypothalamic GnRH and kisspeptin levels increased, while RFRP3 and GPR147 levels decreased, luteinizing hormone levels elevated, reproductive organ coefficients increased, and the vagina opened earlier compared to the normal group. Conversely, the NYRF group exhibited lower GnRH and kisspeptin levels but higher RFRP3 levels in the hypothalamus. Serum luteinizing hormone levels were reduced, reproductive organ coefficients were reduced, and the vaginal opening was delayed compared to the model and normal saline groups. Conclusion: The NYRF herbal mixture delayed sexual development in rats with PP by hypothalamic upregulating RFRP3 and downregulating GnRH and kisspeptin.
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Egg production is an economically important trait in poultry breeding and production. Follicular development was regulated by several hormones released and genes expressed in the granulosa cells, impacting the egg production and fecundity of hens. However, the molecular functions of these candidate genes that modulate these processes remain largely unknown. In the present study, bioinformatics analyses were performed to identify the candidate genes related to egg production in the ovarian tissue of White Leghorns with high egg production and Beijing You chicken with low egg production during sexual maturity and peak laying periods. The ovarian granulosa cells were used to assess the function of CYP21A1 by transfecting with CYP21A1-specific small interfering RNAs (siRNAs) and overexpression plasmids. We identified 514 differentially expressed genes (|Log2(fold change) | >1, P <0.05) between the 2 chicken breeds in both laying periods. Among these genes, CYP21A1, which is involved in the steroid hormone biosynthesis pathway was consistently upregulated in White Leghorns. Weighted gene co-expression network analysis (WGCNA) further suggested that CYP21A1 was a hub gene, which could positively respond to treatment with follicle stimulation hormone (FSH), affecting egg production. The interference of CYP21A1 significantly inhibited cell proliferation and promoted cell apoptosis. Overexpression of CYP21A1 promotes cell proliferation and inhibits cell apoptosis. Furthermore, the interference with CYP21A1 significantly downregulated the expression of STAR, CYP11A1, HSD3B1, and FSHR and also decreased the synthesis of progesterone (P4) and estradiol (E2) in granulosa cells. Overexpression of CYP21A1 increased the synthesis of P4 and estradiol E2 and the expression of steroid hormone synthesis-related genes in granulosa cells. Our findings provide new evidence for the biological role of CYP21A1 on granulosa cell proliferation, apoptosis, and steroid hormone synthesis, which lays the theoretical basis for improving egg production.
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Galinhas , Perfilação da Expressão Gênica , Células da Granulosa , Animais , Feminino , Galinhas/genética , Galinhas/fisiologia , Células da Granulosa/metabolismo , Células da Granulosa/fisiologia , Perfilação da Expressão Gênica/veterinária , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Ovário/metabolismo , Hormônios Esteroides Gonadais/biossíntese , Hormônios Esteroides Gonadais/metabolismo , Transcriptoma , Folículo Ovariano/metabolismo , Folículo Ovariano/fisiologiaRESUMO
Trichomonas gallinae (T. gallinae) is a globally distributed protozoan parasite and could cause serious damage to the pigeon industry. MiRNAs have important roles in regulating parasite infection, but its impacts on T. gallinae resistance have rarely been reported. In the present study, we identified a new miRNA (novel-miR-741) and its predicted target OTU deubiquitinase 1 (OTUD1) that might be associated with immunity to T. gallinae in pigeon. Novel-miR-741 and OTUD1 over-expression vectors and interference vectors were constructed. Results from dual luciferase activity assay demonstrated that OTUD1 was a downstream target of novel-miR-741. The Cell Counting Kit-8 and apoptosis assays showed that novel-miR-741 inhibited the proliferation and promoted apoptosis of pigeon crop fibroblasts. Meanwhile, mRNA levels of OTUD1 were significantly reduced in novel-miR-741 mimic-transfected fibroblasts, while mRNA levels of OTUD1 were significantly increased in the novel-miR-741 inhibitor-transfected fibroblasts. The regulatory roles of si-OTUD1 on fibroblasts proliferation, apoptosis, and migration were similar to novel-miR-741 mimic. Our findings demonstrated that novel-miR-741 inhibited the proliferation, and migration of crop fibroblasts, while OTUD1 promoted the proliferation and migration of crop fibroblasts. Therefore, the regulation of OTUD1 by novel-miR-741 was proposed as a potential therapeutic strategy for T. gallinae.
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Apoptose , Proliferação de Células , Columbidae , Fibroblastos , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Fibroblastos/fisiologia , Columbidae/fisiologia , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismoRESUMO
Quercetin (Quer) is a natural flavonoid known for its inhibitory effects against various cancers. However, the mechanism by which Quer inhibits gastric cancer (GC) has not yet been fully elucidated. Ferroptosis, a mode of programmed cell death resulting from lipid peroxidation, is regulated by abnormalities in the antioxidant system and iron metabolism. Through flow cytometry and other detection methods, we found that Quer elevated lipid peroxidation levels in GC cells. Transmission electron microscopy confirmed an increase in ferroptosis in Quer-induced GC. We demonstrated that Quer inhibits SLC1A5 expression. Molecular docking revealed Quer's binding to SLC1A5 at SER-343, SER-345, ILE-423, and THR-460 residues. Using immunofluorescence and other experiments, we found that Quer altered the intracellular ROS levels, antioxidant system protein expression levels, and iron content. Mechanistically, Quer binds to SLC1A5, inhibiting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), resulting in decreased xCT/GPX4 expression. Quer/SLC1A5 signaling activated p-Camk2, leading to upregulated p-DRP1 and enhanced ROS release. Additionally, Quer increased the intracellular iron content by inhibiting SLC1A5. These three changes collectively led to ferroptosis in GC cells. In conclusion, Quer targets SLC1A5 in GC cells, inhibiting the NRF2/xCT pathway, activating the p-Camk2/p-DRP1 pathway, and accelerating iron deposition. Ultimately, Quer promotes ferroptosis in GC cells, inhibiting GC progression. Overall, our study reveals that Quer can potentially impede GC progression by targeting SLC1A5, offering novel therapeutic avenues through the modulation of ferroptosis and iron homeostasis.
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Ferroptose , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Quercetina/farmacologia , Fator 2 Relacionado a NF-E2/genética , Antioxidantes , Ferroptose/genética , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio , Ferro , Antígenos de Histocompatibilidade Menor , Sistema ASC de Transporte de AminoácidosRESUMO
Heterosis has been widely utilized in chickens. The nonadditive inheritance of genes contributes to this biological phenomenon. However, the role of circRNAs played in the heterosis is poorly determined. In this study, we observed divergent heterosis for residual feed intake (RFI) between 2 crossbreds derived from a reciprocal cross between White Leghorns and Beijing You chickens. Then, circRNA landscape for 120 samples covering the hypothalamus, liver, duodenum mucosa and ovary were profiled to elucidate the regulatory mechanisms of heterosis. We detected that a small proportion of circRNAs (7.83-20.35%) were additively and non-additively expressed, in which non-additivity was a major inheritance of circRNAs in the crossbreds. Tissue-specific expression of circRNAs was prevalent across 4 tissues. Weighted gene co-expression network analysis revealed circRNA-mRNA co-expression modules associated with feed intake and RFI in the hypothalamus and liver, and the co-expressed genes were enriched in oxidative phosphorylation pathway. We further identified 8 nonadditive circRNAs highly correlated with 16 nonadditive genes regulating negative heterosis for RFI in the 2 tissues. Circ-ITSN2 was validated in the liver tissue for its significantly positive correlation with PGPEP1L. Moreover, the bioinformatic analysis indicated that candidate circRNAs might be functioned by binding the microRNAs and interacting with the RNA binding proteins. The integration of multi-tissue transcriptome firstly linked the association between tissue-specific circRNAs and the heterosis for feed intake and efficiency in chicken, which provide novel insights into the molecular mechanism underlying heterosis for feed efficiency. The validated circRNAs can act as potential biomarkers for predicting RFI and its heterosis.