RESUMO
Traumatic brain injury (TBI) and stroke share a common pathophysiology that worsens over time due to secondary tissue injury caused by sustained inflammatory response. However, studies on pharmacological interventions targeting the complex secondary injury cascade have failed to show efficacy. Here, we demonstrated that low-dose ionizing radiation (LDIR) reduced lesion size and reversed motor deficits after TBI and photothrombotic stroke. Magnetic resonance imaging demonstrated significant reduction of infarct volume in LDIR-treated mice after stroke. Systems-level transcriptomic analysis showed that genes upregulated in LDIR-treated stoke mice were enriched in pathways associated with inflammatory and immune response involving microglia. LDIR induced upregulation of anti-inflammatory- and phagocytosis-related genes, and downregulation of key pro-inflammatory cytokine production. These findings were validated by live-cell assays, in which microglia exhibited higher chemotactic and phagocytic capacities after LDIR. We observed substantial microglial clustering at the injury site, glial scar clearance and reversal of motor deficits after stroke. Cortical microglia/macrophages depletion completely abolished the beneficial effect of LDIR on motor function recovery in stroke mice. LDIR promoted axonal projections (brain rewiring) in motor cortex and recovery of brain activity detected by electroencephalography recordings months after stroke. LDIR treatment delayed by 8 h post-injury still maintained full therapeutic effects on motor recovery, indicating that LDIR is a promising therapeutic strategy for TBI and stroke.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Acidente Vascular Cerebral , Camundongos , Animais , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Acidente Vascular Cerebral/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Microglia/metabolismo , Radiação Ionizante , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: The assessment of skin aging through skin measurements faces limitations, making perceived age evaluation a more valuable and direct tool for assessing skin aging. Given that the aging process markedly affects the appearance of the eye contour, characterizing the eye region could be beneficial for perceived age assessment. This study aimed to analyze age-correlated changes in the eye contour within the Chinese Han female population and to develop, validate, and apply a multiple linear regression model for predicting perceived age. MATERIALS AND METHODS: A naïve panel of 107 Chinese women assessed the perceived ages of 212 Chinese Han women. Instrumental analysis evaluated periorbital parameters, including palpebral fissure width (PFW), palpebral fissure height (PFH), acclivity of palpebral fissure (AX), angle of inner canthal (AEN), and angle of outer canthal (AEX). These parameters were used to construct a multiple linear regression model for predicting the perceived ages of Chinese Han women. A combined treatment using Fotona 4D and an anti-aging eye cream, formulated with plant extracts, peptides, and antioxidants, was conducted to verify the cream's anti-aging efficacy and safety. This eye cream was then tested in a large-scale clinical trial involving 101 participants. The prediction model was employed in this trial to assess the perceived ages of the women after an 8-week application of the eye cream. RESULTS: All parameters were observed to decrease with age. An intergroup comparison indicated that eyelid aging in Chinese Han women accelerates beyond the age of 50. Consequently, a linear regression model was constructed and validated, with the perceived age being calculated as 183.159 - 1.078 * AEN - 4.487 * PFW + 6.061 * PFH - 1.003 * AX - 0.328 * AEX. The anti-aging efficacy and safety of the eye cream were confirmed through combined treatment with Fotona 4D, showing improvements in wrinkles, elasticity, and dark circles under the eyes. In a large-scale clinical evaluation using this eye cream, a perceived age prediction model was applied, suggesting that 8 weeks of use made participants appear 2.25 years younger. CONCLUSION: Our study developed and validated a multiple linear regression model to predict the perceived age of Chinese Han women. This model was successfully utilized in a large-scale clinical evaluation of anti-aging eye cream, revealing that 8 weeks of usage made participants appear 2.25 years younger. This method effectively bridges the gap between clinical research and consumer perceptions, explores the complex factors influencing perceived age, and aims to improve anti-aging formulations.
Assuntos
Povo Asiático , Envelhecimento da Pele , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , China/etnologia , População do Leste Asiático , Olho , Modelos Lineares , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/fisiologia , Envelhecimento da Pele/etnologia , Creme para a Pele/administração & dosagemRESUMO
OBJECTIVES: To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder (CFD). METHODS: A retrospective analysis was conducted on the clinical data of 16 children with CFD. Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA, FGB, and FGG genes, and sequencing was performed to analyze mutation characteristics. RESULTS: Among the 16 children, there were 9 boys (56%) and 7 girls (44%), with a median age of 4 years at the time of attending the hospital. Among these children, 9 (56%) attended the hospital due to bleeding events, and 7 (44%) were diagnosed based on preoperative examination. The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events (P<0.05). Genetic testing was conducted on 12 children and revealed a total of 12 mutations, among which there were 4 novel mutations, i.e., c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene. There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene, with relatively severe bleeding symptoms. There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes, and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding. CONCLUSIONS: The clinical phenotypes of children with CFD are heterogeneous, and the severity of bleeding is associated with the level of fibrinogen activity, but there is a weak association between clinical phenotype and genotype.
Assuntos
Afibrinogenemia , Fibrinogênio , Genótipo , Mutação , Fenótipo , Humanos , Masculino , Feminino , Afibrinogenemia/genética , Pré-Escolar , Criança , Fibrinogênio/genética , Lactente , Estudos Retrospectivos , Adolescente , Hemorragia/genética , Hemorragia/etiologiaRESUMO
Covering: up to 202216.19% of reported natural products (NPs) in the Dictionary of Natural Products (DNP) are glycosides. As one of the most important NPs' structural modifications, glycosylation can change the NPs' polarity, making the aglycones more amphipathic. However, until now, little is known about the general distribution profile of the natural glycosides in different biological sources or structural types. The reason, structural or species preferences of the natural glycosylation remain unclear. In this highlight, chemoinformatic methods were employed to analyze the natural glycosides from DNP, the most comprehensively annotated NP database. We found that the glycosylation ratios of NPs from plants, bacteria, animals and fungi decrease successively, which are 24.99%, 20.84%, 8.40% and 4.48%, respectively. Echinoderm-derived NPs (56.11%) are the most frequently glycosylated, while those produced by molluscs (1.55%), vertebrates (2.19%) and Rhodophyta (3.00%) are the opposite. Among the diverse structural types, a large proportion of steroids (45.19%), tannins (44.78%) and flavonoids (39.21%) are glycosides, yet aminoacids and peptides (5.16%), alkaloids (5.66%) are comparatively less glycosylated. Even within the same biological source or structural type, their glycosylation rates fluctuate drastically between sub- or cross-categories. The substitute patterns of flavonoid and terpenoid glycosides and the most frequently glycosylated scaffolds were identified. NPs with different glycosylation levels occupy different chemical spaces of physicochemical property and scaffold. These findings could help us to interpret the preference of NPs' glycosylation and investigate how NP glycosylation could aid NP-based drug discovery.
Assuntos
Produtos Biológicos , Glicosídeos , Animais , Glicosídeos/química , Quimioinformática , Flavonoides/química , Plantas , Extratos Vegetais , Produtos Biológicos/químicaRESUMO
The genus Culicoides includes biting midges, some of which are vectors for viruses that cause diseases in humans and animals. Knowledge of the roles of Culicoides in viral ecology is inadequate. We collected ~300 000 samples of Culicoides and mosquitoes in 15 representative regions within Yunnan, China. Using mosquitoes as reference vectors, we designed a comparative virome strategy to study the viral composition, diversity, hosts and spatiotemporal distribution of Culicoides. A map of viromes in Culicoides and mosquitoes in Yunan province, China, was constructed. At the same locations, Culicoides and mosquitoes usually share a similar viral diversity. At least 10 important pathogenic viruses were detected from Culicoides. Many novel viruses were discovered, including 21 segmented viruses of Flaviviridae, 180 viruses of Monjiviricetes and 130 viruses of Bunyavirales. The findings demonstrate that Culicoides is an important part of viral ecology and should be studied and monitored for potentially emerging viruses.
Assuntos
Ceratopogonidae/virologia , Culicidae/virologia , Vírus de RNA de Cadeia Positiva/classificação , Viroma , AnimaisRESUMO
Vancomycin (VAN), meropenem (MER), and valproate (VPA) are commonly used to treat intracranial infection post-craniotomy and prevent associated epilepsy. To monitor their levels, we developed a novel bioassay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous determination of these three drugs in human serum and cerebrospinal fluid (CSF). Sample preparation by protein precipitation using acetonitrile was followed by HPLC on a Zorbax 300SB-C8 column (150 mm × 4.6 mm, 5 µm) maintained at 40 °C. The lower limit of quantification (LLOQ) was 5 ng/mL for MER, 0.1 µg/mL for VAN, and 1 µg/mL for VPA in serum and 50 ng/mL for MER, 1 µg/mL for VAN, and 2 µg/mL for VPA in CSF. This method was validated with satisfactory linearity, sensitivity, precision, accuracy, recovery, matrix effects, and stability for all analytes. The assay was then successfully applied to evaluate VPA, MER, and VAN levels in serum and CSF from patients with intracranial infection administrated by intrathecal injection. Compared with intravenous injections, an intrathecal injection can provide sufficient therapeutic effects even if the CSF levels did not reach the effective concentration reported. Our method provided a detection tool to study the effective concentrations of these three drugs in CSF from patients administered via intrathecal injection.
Assuntos
Ácido Valproico , Vancomicina , Humanos , Ácido Valproico/química , Cromatografia Líquida de Alta Pressão/métodos , Meropeném , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Limite de Detecção , Reprodutibilidade dos TestesRESUMO
Electrobiocorrosion, the process in which microbes extract electrons from metallic iron (Fe0 ) through direct Fe0 -microbe electrical connections, is thought to contribute to the costly corrosion of iron-containing metals that impacts many industries. However, electrobiocorrosion mechanisms are poorly understood. We report here that electrically conductive pili (e-pili) and the conductive mineral magnetite play an important role in the electron transfer between Fe0 and Geobacter sulfurreducens, the first microbe in which electrobiocorrosion has been rigorously documented. Genetic modification to express poorly conductive pili substantially diminished corrosive pitting and rates of Fe0 -to-microbe electron flux. Magnetite reduced resistance to electron transfer, increasing corrosion currents and intensifying pitting. Studies with mutants suggested that the magnetite promoted electron transfer in a manner similar to the outer-surface c-type cytochrome OmcS. These findings, and the fact that magnetite is a common product of iron corrosion, suggest a potential positive feedback loop of magnetite produced during corrosion further accelerating electrobiocorrosion. The interactions of e-pili, cytochromes, and magnetite demonstrate mechanistic complexities of electrobiocorrosion, but also provide insights into detecting and possibly mitigating this economically damaging process.
Assuntos
Óxido Ferroso-Férrico , Geobacter , Oxirredução , Elétrons , Corrosão , Transporte de Elétrons , Citocromos/metabolismo , Ferro , Geobacter/genética , Geobacter/metabolismoRESUMO
Giant axonal neuropathy (GAN) is a progressive disease that involves the peripheral and central nervous systems. This neurodegenerative disease is caused by variants in the GAN gene encoding gigaxonin, and is inherited in an autosomal recessive manner. Herein, we performed whole-exome sequencing on a 8-year-old child with dense, curly hair, weakness in both lower limbs, and abnormal MRI. The child was born to consanguineous parents. Our results revealed that the child carried the c.1373+1G>A homozygous pathogenic variant of the GAN gene, while both parents were heterozygous carriers. According to the validation at the cDNA levels, the splicing variant led to the skipping of exon 8 and affected the Kelch domain's formation. Unlike the previously reported cases of GAN, the child's clinical manifestations revealed peripheral nervous system involvement, no vertebral signs, cerebellar signs, and spasticity, but only MRI abnormalities. These results suggested that the patient's central nervous system was mildly involved, which may be related to the genotype. In order to further clarify the correlation between GAN genotype and phenotype, combined with this patient, 54 cases of reported homozygous variants of the GAN gene were merged for the analysis of genotype and phenotype. The results revealed a certain correlation between the GAN gene variant domain and the patient's clinical phenotype, such as central nervous system involvement and age of onset.
Assuntos
Neuropatia Axonal Gigante , Doenças Neurodegenerativas , Consanguinidade , Proteínas do Citoesqueleto/genética , Neuropatia Axonal Gigante/genética , Neuropatia Axonal Gigante/patologia , Homozigoto , HumanosRESUMO
The scarcity of water resources has led to widespread interest in the treatment of oily wastewater. This study prepared a novel superhydrophilic/underwater superoleophobic polysulfonamide (PSA)/polyvinylpyrrolidone (PVP) nanofibrous membrane through electrostatic spinning for efficient oil-water emulsion separation. The surface morphology, fiber diameter distribution, wettability properties, and oil-water emulsion separation performance of the membranes were investigated. Results showed that the addition of PVP increases the diameter of the fibers, which led to a loose, large, porous structure and improved the permeability of the membranes. A high pure-water flux of 2057 L·m-2·h-1 was obtained for membranes with PVP addition of 3 wt%, providing an 835% increase in pure-water flux compared with a pure PSA nanofibrous membrane (220 L·m-2·h-1). For n-hexane-in-water emulsions, the optimum membrane obtained a high separation efficiency of 99.7%, in which flux was 1.5 times greater than that of the pure PSA nanofibrous membrane. Moreover, the optimum membrane exhibited good recycling stability and solvent resistance. The as-prepared PSA/PVP nanofibrous membrane displayed high permeability, an outstanding rejection rate, resistance to organic solvents, and reusability for oil-water separation, providing great potential in practical membrane separation applications.
RESUMO
A novel fluorescence platform was fabricated for enrofloxacin determination by using cDNA-modified dipeptide fluorescence nanoparticles (FDNP-cDNA) and aptamer-modified magnetic Fe3O4 nanoparticles (Fe3O4-Apt). The FDNP were prepared via tryptophan-phenylalanine self-assembling. When magnetic Fe3O4-Apt incubated with standard solution or sample extracts, the target enrofloxacin was selectively captured by the aptamer on the surface of the Fe3O4 nanoparticles. After removing interference by washing with phosphate-buffered saline, the FDNP-cDNA was added, which can bind to the aptamer on the surface of the Fe3O4 nanoparticles not occupied by the analyte. The higher the concentration of the target enrofloxacin in the standard or sample solution is, the less the FDNP-cDNA can be bound with the Fe3O4 nanoparticles, and the more the FDNP-cDNA can be observed in the supernatant. Fluorescence intensity (Ex/Em = 310/380 nm) increased linearly in the enrofloxacin concentration range 0.70 to 10.0 ng/mL with a detection limit of 0.26 ng/mL (S/N = 3). Good recoveries (88.17-99.30%) were obtained in spiked lake water, chicken, and eel samples with relative standard deviation of 2.7-6.2% (n = 3).
Assuntos
Aptâmeros de Nucleotídeos/química , Dipeptídeos/química , Enrofloxacina/análise , Corantes Fluorescentes/química , Nanopartículas/química , Poluentes Químicos da Água/análise , Animais , Técnicas Biossensoriais , Galinhas , DNA Complementar/química , Enguias , Lagos , Espectrometria de FluorescênciaRESUMO
Twelve novel cordycepin derivatives were designed and synthesized with modification at positions of 2', 5'-hydroxyl and N6 amino groups of cordycepin. The results showed that the inhibitory activities of 3, 4b, 6c and 6d on A549 were comparable to the positive control gefitinib, and the inhibitory activity of 6a on A549 was better than that of gefitinib. Also, the inhibitory activities of twelve cordycepin derivatives against E. coli 1924, S. aureus 4220 and S. mutans 3289 were studied. Among them, 4b showed certain inhibitory on S. mutans 3289, while 6b showed certain inhibition on S. aureus 4220.
Assuntos
Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Desoxiadenosinas , Gefitinibe , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Subtype-selective drugs are of great therapeutic importance as they are expected to be more effective and with less side-effects. However, discovery of subtype selective inhibitors was hampered by the high similarity of the binding sites within subfamilies. In this study, we further evaluated the applicability of "Three-Dimensional Biologically Relevant Spectrum (BRS-3D)" for the identification of subtype-selective inhibitors. A case study was performed on monoamine oxidase, which has two subtypes related to distinct diseases. The inhibitory activity against MAO-A/B of 347 compounds experimentally tested in this research was reported. Compound M124 (5H-thiazolo[3,2-a]pyrimidin-5-one) with IC50 less than 100 nM (SI = 23) was selected as a probe to investigate the structure selectivity relationship. Similarity search led to the identification of compound M229 and M249 with IC50 values of 7.4 nM, 4 nM and acceptable selectivity index over MAO-A (M229 SI > 1351, M249 SI > 2500). The molecular basis for subtype selectivity was explored through docking study and attention based DNN model. Additionally, in silico ADME properties were characterized. Accordingly, it is found that BRS-3D is a robust method for subtype selectivity in the early stage of drug discovery and the compounds reported here can be promising leads for further experimental analysis.
Assuntos
Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Máquina de Vetores de Suporte , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Inibidores da Monoaminoxidase/química , Relação Estrutura-AtividadeRESUMO
The Hippo pathway, an evolutionarily conserved protein kinase cascade, tightly regulates cell growth and survival. Activation of yes-associated protein (YAP), a downstream effector of the Hippo pathway, has been shown to modulate tissue inflammation. However, it remains unknown as to whether and how the Hippo-YAP signaling may control NLR family pyrin domain containing 3 (NLRP3) activation in mesenchymal stem cell (MSC)-mediated immune regulation during liver inflammation. In a mouse model of ischemia/reperfusion (IR)-induced liver sterile inflammatory injury, we found that adoptive transfer of MSCs reduced hepatocellular damage, shifted macrophage polarization from M1 to M2 phenotype, and diminished inflammatory mediators. MSC treatment reduced mammalian Ste20-like kinase 1/2 and large tumor suppressor 1 phosphorylation but augmented YAP and ß-catenin expression with increased prostaglandin E2 production in ischemic livers. However, disruption of myeloid YAP or ß-catenin in MSC-transferred mice exacerbated IR-triggered liver inflammation, enhanced NLRP3/caspase-1 activity, and reduced M2 macrophage phenotype. Using MSC/macrophage coculture system, we found that MSCs increased macrophage YAP and ß-catenin nuclear translocation. Importantly, YAP and ß-catenin colocalize in the nucleus while YAP interacts with ß-catenin and regulates its target gene X-box binding protein 1 (XBP1), leading to reduced NLRP3/caspase-1 activity after coculture. Moreover, macrophage YAP or ß-catenin deficiency augmented XBP1/NLRP3 while XBP1 deletion diminished NLRP3/caspase-1 activity. Increasing NLRP3 expression reduced M2 macrophage arginase1 but augmented M1 macrophage inducible nitric oxide synthase expression accompanied by increased interleukin-1ß release. Conclusion: MSCs promote macrophage Hippo pathway, which in turn controls NLRP3 activation through a direct interaction between YAP and ß-catenin and regulates XBP1-mediated NLRP3 activation, leading to reprograming macrophage polarization toward an anti-inflammatory M2 phenotype. Moreover, YAP functions as a transcriptional coactivator of ß-catenin in MSC-mediated immune regulation. Our findings suggest a therapeutic target in MSC-mediated immunotherapy of liver sterile inflammatory injury.
Assuntos
Fígado/irrigação sanguínea , Células-Tronco Mesenquimais/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Traumatismo por Reperfusão/imunologia , Transdução de Sinais/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Proteínas de Ciclo Celular/fisiologia , Células Cultivadas , Macrófagos/fisiologia , Camundongos , Proteínas de Sinalização YAPRESUMO
BACKGROUND & AIMS: Recently, the variant rs72613567:TA in the 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) has been associated with reduced levels of ALT and AST and a reduced risk of alcohol-related liver disease (ALD) in the European population. Therefore, the aim of this study was to investigate the association between the polymorphisms of HSD17B13 and ALD, liver serum markers and patatin-like phospholipase domain-containing protein 3 (PNPLA3) p.I148M in the Chinese Han population. METHODS: A case-control study was performed from five centres and included 769 ALD patients and 767 healthy controls. Two SNPs (rs72613567 and rs6834314) in HSD17B13 were genotyped using the Sequenom MassArray system and allele association analysis was performed using PLINK 1.90 software. RESULTS: HSD17B13 rs72613567:TA allele was associated with a reduced risk of ALD by 19% (95% confidence interval [CI]: 0.05-0.31, P = .01), uniformly, the G allele in the rs6834314 reduced the risk of ALD by 19% (95% CI: 0.05-0.31, P = 8.28 × 10-3). And the genotypes of two SNPs were associated with reducing the risk of ALD in three genetic model analysis. In addition, we found that TA allele was associated with lower levels of serum ALT, AST and GGT (P = .005, .007 and .02, respectively), higher level of serum ALB (P = .02), but not associated with ALP. In this cohort, the interaction between HSD17B13 rs72613567 and the steatogenic allele PNPLA3 rs738409 was not validated. CONCLUSION: The present study revealed that HSD17B13 rs72613567 was significantly associated with a reduced risk of ALD in Chinese Han population.
Assuntos
Hepatopatias , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Humans are exposed to polybrominated diphenyl ethers (PBDEs) via ingestion of food, dust inhalation, and dermal absorption. Exposure to PBDEs via the placenta and breast milk is a special and important pathway in infants. This nested case-control study aimed to investigate the levels of PBDEs in maternal serum and colostrum, and to assess the association between the occurrence of fetal growth restriction (FGR) and prenatal exposure to PBDEs. We recruited 293 mother-newborn pairs, including 98 FGR cases and 195 healthy controls in Wenzhou, China. Maternal serum and colostrum samples were collected during pregnancy and after delivery, respectively, and the levels of PBDEs were measured by gas chromatography-tandem mass spectrometry. The total levels of PBDEs in maternal serum and colostrum were found to be in equilibrium, but congener profiles of PBDEs in these matrices were different. Increased BDE-207, BDE-209, ∑BDE196-209 and ∑PBDEs levels in maternal serum and BDE-99, ∑BDE17-154 and ∑PBDEs levels in colostrum were correlated with decreased birth weight Z score. Increased concentrations of higher brominated BDEs in maternal serum (odds ratio (OR) = 1.010, 95%CI = 1.003-1.018) and low-to moderately brominated BDEs in colostrum (OR = 1.004, 95%CI = 1.000-1.009) were associated with increased risk of FGR, which showed an exposure-response relationship. In addition, infants with FGR were more exposed to PBDEs in colostrum after birth than healthy infants. Longitudinal birth cohort studies are needed to determine the prolonged effect of PBDEs exposure on the growth of FGR infants in the future.
Assuntos
Retardo do Crescimento Fetal/induzido quimicamente , Éteres Difenil Halogenados/toxicidade , Exposição Materna , Estudos de Casos e Controles , China , Colostro/química , Poluentes Ambientais/toxicidade , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Éteres Difenil Halogenados/sangue , Humanos , Recém-Nascido , Leite Humano/química , Placenta/efeitos dos fármacos , Placenta/metabolismo , GravidezRESUMO
Breast cancer is the most common female malignant tumors in the world. It seriously affects women's physical and mental health and the leading cause of cancer death among women. Our previous study demonstrated that diet-derived IFN-γ promoted the malignant transformation of primary bovine mammary epithelial cells by accelerating arginine depletion. The current study aimed to explore whether arginine addition could inhibit the degree of malignant transformation and its molecular mechanism. The results indicate that arginine addition could alleviate the malignant transformation of mammary epithelial cells induced by IFN-γ, including reducing cell proliferation, cell migration and colony formation, through the NF-κB-GCN2/eIF2α pathway. The in vivo experiments also consistently confirmed that arginine supplementation could significantly inhibit tumor growth in tumor-bearing mice. Furthermore, the investigation of the clinical data also revealed that the plasma or tissue from human breast cancer patients owned lower arginine level and higher IFN-γ level than that from patients with benign breast disease, showing IFN-γ may be a potential control target. Our findings demonstrate that arginine supplement could antagonize the malignant transformation of mammary epithelial cells induced by IFN-γ (nutritionally induced) both in vitro and in vivo, and IFN-γ was higher in breast cancer women. This might provide a novel strategy for the prevention and treatment of breast cancer regarding to nutrition.
Assuntos
Arginina/metabolismo , Transformação Celular Neoplásica/metabolismo , Células Epiteliais/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Interferon gama/metabolismo , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Mama/metabolismo , Neoplasias da Mama/metabolismo , Bovinos , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Humanos , Camundongos , Transporte Proteico/fisiologia , Transdução de Sinais/fisiologiaRESUMO
Methyl farnesoate (MF), the crustacean juvenile hormone (JH), plays critical roles in various physiological processes in crustaceans. The titer of MF is precisely regulated by specific carboxylesterase. Here, we report for the first time that the cloning and expression analysis of a JH esterase-like carboxylesterase from the prawn Macrobrachium rosenbergii (named as MrCXE). MrCXE contained a 1935-bp open reading frame (ORF) conceptually translated into a 644-amino acids protein. MrCXE protein shared the highest identity (36%) with JH esterase-like carboxylesterase from the swimming crab, Portunus trituberculatus and exhibited the typical motifs of JH esterase-like carboxylesterases. MrCXE was most abundantly expressed in hepatopancreas, the major tissue for MF metabolism. MrCXE was expressed at a low level in gut and was not detected in other tissues. Additionally, MrCXE expression was upregulated in hepatopancreas by eyestalk ablation to increase MF level. Furthermore, the mRNA level of MrCXE was significantly increased in the hepatopancreas when challenged by the bacterial pathogens Aeromonas hydrophila and Vibrio parahaemolyticus. To our knowledge, this is the first report that the JH esterase-like carboxylesterase is involved in the innate immune response of the crustaceans.
Assuntos
Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/imunologia , Palaemonidae/genética , Palaemonidae/imunologia , Aeromonas hydrophila , Sequência de Aminoácidos , Animais , Clonagem Molecular , DNA Complementar/genética , Feminino , Expressão Gênica , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Hepatopâncreas/imunologia , Masculino , RNA Mensageiro/metabolismo , Vibrio parahaemolyticusRESUMO
Microbiologically influenced corrosion (MIC) caused by corrosive microorganisms poses significant economic losses and safety hazards. Conventional corrosion prevention methods have limitations, so it is necessary to develop the eco-friendly and long-term effective strategies to mitigate MIC. This study investigated the inhibition of Vibrio sp. EF187016 biofilm on Geobacter sulfurreducens on carbon steel. Vibrio sp. EF187016 biofilm reduced the corrosion current density and impeded pitting corrosion. A thick and uniform Vibrio sp. EF187016 biofilm formed on the coupon surfaces, acting as a protective layer against corrosive ions and electron acquisition by G. sulfurreducens. The pre-grown mature Vibrio sp. EF187016 biofilms, provided enhanced protection against G. sulfurreducens corrosion. Additionally, the extracellular polymeric substances from Vibrio sp. EF187016 was confirmed to act as a green corrosion inhibitor to mitigate microbial corrosion. This study highlights the potential of active biofilms for eco-friendly corrosion protection, offering a novel perspective on material preservation against microbial corrosion.
Assuntos
Cáusticos , Geobacter , Aço , Carbono , Corrosão , Cáusticos/farmacologia , BiofilmesRESUMO
Plant enzymes significantly contribute to the rapidly diversified metabolic repertoire since the colonization of land by plants. Carboxylesterase is just one of the ubiquitous, multifunctional and ancient enzymes that has particularly diversified during plant evolution. This study provided a status on the carboxylesterase landscape within Viridiplantae. A total of 784 carboxylesterases were identified from the genome of 31 plant species representing nine major lineages of sequenced Viridiplantae and divided into five clades based on phylogenetic analysis. Clade I carboxylesterase genes may be of bacterial origin and then expanded and diversified during plant evolution. Clade II was first gained in the ancestor of bryophytes after colonization of land by plants, Clade III and Clade IV in ferns which were considered the most advanced seedless vascular plants, while Clade V was gained in seed plants. To date, the functions of carboxylesterase genes in woody plants remain unclear. In this study, 51 carboxylesterase genes were identified from the genome of Populus trichocarpa and further divided into eight classes. Tandem and segmental duplication events both contributed to the expansion of carboxylesterase genes in Populus. Although carboxylesterase genes were proven to enhance resistance to pathogens in many herbaceous species, relevant researches on forest trees are still needed. In this study, pathogen incubation assays showed that overexpressing of six Class VI carboxylesterases in Populus tomentosa, to a greater or lesser degree, reduced colonization of detached leaves by fungus Cytospora chrysosperma. A significant difference was also found in functional divergence patterns for genes derived from different gene duplication events. Functional differentiation of duplicated carboxylesterase genes in Populus was proved for the first time by in vivo physiological analysis. The identification of the potentially anti-fungal PtoCXE06 gene also laid a theoretical foundation for promoting the genetic improvement of disease-resistance traits in forest trees.
Assuntos
Plantas Geneticamente Modificadas , Populus , Populus/genética , Populus/microbiologia , Plantas Geneticamente Modificadas/genética , Filogenia , Evolução Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Família Multigênica , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismoRESUMO
Object detector based on fully convolutional network achieves excellent performance. However, existing detection algorithms still face challenges such as low detection accuracy in dense scenes and issues with occlusion of dense targets. To address these two challenges, we propose an Global Remote Feature Modulation End-to-End (GRFME2E) detection algorithm. In the feature extraction phase of our algorithm, we introduces the Concentric Attention Feature Pyramid Network (CAFPN). The CAFPN captures direction-aware and position-sensitive information, as well as global remote dependencies of features in deep layers by combining Coordinate Attention and Multilayer Perceptron. These features are used to modulate the front-end shallow features, enhancing inter-layer feature adjustment to obtain comprehensive and distinctive feature representations.In the detector part, we introduce the Two-Stage Detection Head (TS Head). This head employs the First-One-to-Few (F-O2F) module to detect slightly or unobstructed objects. Additionally, it uses masks to suppress already detected instances, and then feeds them to the Second-One-to-Few (S-O2F) module to identify those that are heavily occluded. The results from both detection stages are merged to produce the final output, ensuring the detection of objects whether they are slightly obscured, unobstructed, or heavily occluded. Experimental results on the pig detection dataset demonstrate that our GRFME2E achieves an accuracy of 98.4%. In addition, more extensive experimental results show that on the CrowdHuman dataset, our GRFME2E achieves 91.8% and outperforms other methods.