RESUMO
PURPOSE: The aim of this study was to examine the associations between body composition and temporal eating patterns, including time of first eating occasion, time of last eating occasion, eating window, and eating jet lag (the variability in meal timing between weekdays and weekends). METHODS: A total of 131 participants were included in the study. Temporal eating pattern information was collected through consecutive 7-day eat timing questionnaires and photographic food records. Body composition was assessed by bioelectrical impedance analysis. Multiple linear regression models were used to evaluate the relationships of temporal eating patterns with body composition, and age was adjusted. Eating midpoint was additionally adjusted in the analysis of eating window. RESULTS: On weekdays, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with lower body fat percentage. On weekends, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with higher FFMI. Longer first eating occasion jet lag was associated with lower lean mass. CONCLUSION: Our study suggested that earlier and more regular eating patterns may have a benefit on body composition.
RESUMO
OBJECTIVE: With the rapid improvements in drone technology, there is an increasing interest in distal pointing to diffuse drones. This study investigated the effect of depth on distal pointing when the hand does not traverse the entire distance from start to target so that the most suitable mathematical model can be assessed. BACKGROUND: Starting from the Fitts paradigm, researchers have proposed different models to predict movement time when the distance to the target is variable. They do consider distance, but they are based on statistical modeling rather than the underlying control mechanisms. METHODS: Twenty-four participants volunteered for an experiment in a full-factorial Fitts' paradigm task (3 levels of movement amplitude *7 levels of target width *3 levels of distance from participant to screen). Movement time and the number of errors were the dependent variables. RESULTS: Depth has a significant effect when the target width is small, but depth has no effect when the target width is large. The angular version of the two-part model is superior to the one-part Fitts' model at larger distances. Besides, Index of difficulty for distal pointing, IDDP with adjustable k achieves the best fit even though the model is very sensitive to the value of k and the complexity of the model could be resulting in an overfitting. The result implies that the effects of movement amplitude and target width are not comparable and grouping them to form a dependent index of difficulty can be misleading especially when distance is an added variable. CONCLUSION: The angular version of the two-part model is a viable and meaningful description for distal pointing. Even though the IDDP with adjustable k is the best predictor for movement time when depth is an added variable, there is no physical interpretation for it. APPLICATION: A reasonable predictive model for performance assessments and predictions in distal pointing.
RESUMO
Introduction: Our recent research has demonstrated that social comparison orientation of ability (SCO-ability) is an antecedent of trait competitiveness (TC), and TC mediates the relation between SCO-ability and domain-specific risk-taking. TC is a multi-dimensional trait, therefore we sought to expand on prior research by examining whether SCO-ability predicted two distinct dimensions of TC: hypercompetitive orientation (HCO) and self-development competitive orientation (SDCO). Methods: We investigated how these different dimensions of TC mediated the relation between SCO-ability and both overall and domain-specific risk-taking in two correlational studies of 622 college students (313 males, mean age = 22.10, SD = 2.35) and 717 adult workers (368 males, mean age = 27.92, SD = 5.11). Results: We found that SCO-ability positively predicted HCO. Together, SCO-ability and HCO predicted overall risk-taking and risk-taking in the recreational and ethical domains in both samples. HCO mediated the relation between SCO-ability and both overall risk-taking and risk-taking in the recreational and ethical domains. Additionally, SCO-ability positively predicted SDCO. SCO-ability and SDCO mainly predicted risk-taking in the recreational domain in both studies. SDCO mediated the relation between SCO-ability and risk-taking only in the recreational domain. Discussion: Collectively, the findings above advance our understanding of the relation between competition and risk-taking by using differentiated measures of TC (HCO and SDCO). Our findings suggest that HCO is more strongly related to risk-taking than SDCO, thereby refining the possible role of SCO-ability and TC in predicting overall risk-taking and domain-specific risk-taking.
RESUMO
Artificial light-harvesting systems (LHSs) with a multi-step sequential energy transfer mechanism significantly enhance light energy utilization. Nonetheless, most of these systems exhibit an overall energy transfer efficiency below 80%. Moreover, due to challenges in molecularly aligning multiple donor/acceptor chromophores, systems featuring ≥3-step sequential energy transfer are rarely reported. Here, a series of artificial LHSs is introduced featuring up to 4-step energy transfer mechanism, constructed using a cyclic peptide-based supramolecular scaffold. These LHSs showed remarkably high energy transfer efficiencies (≥90%) and satisfactory fluorescence quantum yields (ranging from 17.6% to 58.4%). Furthermore, the structural robustness of the supramolecular scaffold enables a comprehensive study of these systems, elucidating the associated energy transfer pathways, and identifying additional energy transfer processes beyond the targeted sequential energy transfer. Overall, this comprehensive investigation not only enhances the understanding of these LHSs, but also underscores the versatility of cyclic peptide-based supramolecular scaffolds in advancing energy harvesting technologies.
RESUMO
BACKGROUND: In the Greater Mekong Subregion (GMS), new vector-control tools are needed to target mosquitoes that bite outside during the daytime and night-time to advance malaria elimination. METHODS: We conducted systematic literature searches to generate a bionomic dataset of the main malaria vectors in the GMS, including human blood index (HBI), parity proportion, sac proportion (proportion with uncontracted ovary sacs, indicating the amount of time until they returned to host seeking after oviposition) and the resting period duration. We then performed global sensitivity analyses to assess the influence of bionomics and intervention characteristics on vectorial capacity. RESULTS: Our review showed that Anopheles minimus, An. sinensis, An. maculatus and An. sundaicus display opportunistic blood-feeding behaviour, while An. dirus is more anthropophilic. Multivariate regression analysis indicated that environmental, climatic and sampling factors influence the proportion of parous mosquitoes, and resting duration varies seasonally. Sensitivity analysis highlighted HBI and parity proportion as the most influential bionomic parameters, followed by resting duration. Killing before feeding is always a desirable characteristic across all settings in the GMS. Disarming is also a desirable characteristic in settings with a low HBI. Repelling is only an effective strategy in settings with a low HBI and low parity proportion. Killing after feeding is only a desirable characteristic if the HBI and parity proportions in the setting are high. CONCLUSIONS: Although in general adopting tools that kill before feeding would have the largest community-level effect on reducing outdoor transmission, other modes of action can be effective. Current tools in development which target outdoor biting mosquitoes should be implemented in different settings dependent on their characteristics.
Assuntos
Anopheles , Malária , Controle de Mosquitos , Mosquitos Vetores , Animais , Malária/prevenção & controle , Malária/transmissão , Mosquitos Vetores/fisiologia , Anopheles/fisiologia , Controle de Mosquitos/métodos , Humanos , Comportamento Alimentar , Sudeste Asiático , Modelos TeóricosRESUMO
This study examined the psychometric properties of the Chinese version of the Multidimensional Competitive Orientation Inventory (Ch-MCOI) in adults from Mainland China. A total of 1121 participants (50.6% male; M = 28.86, SD = 8.70) were recruited for this study. All participants completed the Chinese versions of the MCOI, the Connor-Davidson Resilience Scale (CD-RISC), the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), the Almost Perfect Scale-Revised (APS), the Frost Multidimensional Perfectionism Scale (MPS-f), and the Competition Attitude Scale (Ch-CAS). A subsample of 239 participants (50.6% male; M = 32.04, SD = 8.13) completed the Ch-MCOI again after a two-week interval to assess test-retest reliability. Exploratory Structural Equation Modeling (ESEM) yielded a four-factor structure (hyper-competitive orientation, self-developmental competitive orientation, anxiety-driven competition avoidance, and lack of interest toward competition), which was further validated by confirmatory factor analyses with a satisfactory fit. Furthermore, test-retest reliability, internal consistency, and convergent and concurrent validity were also acceptable. Our findings suggest that the Ch-MCOI could be a reliable and valid instrument for assessing the adaptive and maladaptive facets of competitive orientations in the Chinese-speaking population.
Assuntos
Testes Psicológicos , Resiliência Psicológica , Adulto , Humanos , Masculino , Feminino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
The longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Systemic immunosuppression can impair graft function and can also cause severe adverse effects. Here, we report a local immuno-protective strategy to enhance post-transplant persistence of allografts using a mesenchymal stem cell membrane-derived vesicle (MMV)-crosslinked hydrogel (MMV-Gel). MMVs are engineered to upregulate expression of Fas ligand (FasL) and programmed death ligand 1 (PD-L1). The MMVs are retained within the hydrogel by crosslinking. The immuno-protective microenvironment of the hydrogel protects allografts by presenting FasL and PD-L1. The binding of these ligands to T effector cells, the dominant contributors to graft destruction and rejection, results in apoptosis of T effector cells and generation of regulatory T cells. We demonstrate that implantation with MMV-Gel prolongs the survival and function of grafts in mouse models of allogeneic pancreatic islet cells and skin transplantation.
Assuntos
Proteína Ligante Fas , Hidrogéis , Transplante das Ilhotas Pancreáticas , Camundongos Endogâmicos C57BL , Transplante de Pele , Linfócitos T Reguladores , Transplante Homólogo , Animais , Hidrogéis/química , Camundongos , Proteína Ligante Fas/metabolismo , Proteína Ligante Fas/imunologia , Linfócitos T Reguladores/imunologia , Transplante das Ilhotas Pancreáticas/métodos , Transplante de Pele/métodos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Humanos , Masculino , Apoptose/efeitos dos fármacosRESUMO
Neutrophils have both antimicrobial ability and pathogenic effect in the immune system, neutrophil extracellular traps (NETs) formation is one of the representative behaviors of their dual role. NETs formation was triggered by pathogen-related components and pathogen non-related proteins as cytokines to exert its effector functions. Recent studies indicate that the pathogenicity of NETs contributed to several skin diseases such as psoriasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and neutrophilic dermatosis. Especially in neutrophilic dermatosis, a heterogeneous group of inflammatory skin disorders characterized with sterile neutrophilic infiltrate on dermis, NETs formation was reported as the way of participation of neutrophils in the pathogenesis of these diseases. In this review, we describe the different processes of NETs formation, then summarized the most recent updates about the pathogenesis of neutrophilic dermatosis and the participation of NETs, including pyoderma gangrenosum and PAPA syndrome, Behçet syndrome, hidradenitis suppurativa, Sweet Syndrome, pustular dermatosis and other neutrophilic dermatosis. Furthermore, we discuss the link between NETs formation and the development of neutrophilic dermatosis.
RESUMO
Deciphering cellular interactions is essential to both understand the mechanisms underlying a broad range of human diseases, but also to manipulate therapies targeting these diseases. Here, the formation of cell doublets resulting from specific membrane ligand-receptor interactions is discovered. Based on this phenomenon, the study developed DoubletSeeker, a novel high-throughput method for the reliable identification of ligand-receptor interactions. The study shows that DoubletSeeker can accurately identify T cell receptor (TCR)-antigen interactions with high sensitivity and specificity. Notably, DoubletSeeker effectively captured paired TCR-peptide major histocompatibility complex (pMHC) information during a highly complex library-on-library screening and successfully identified three mutant TCRs that specifically recognize the MART-1 epitope. In turn, DoubletSeeker can act as an antigen discovery platform that allows for the development of novel immunotherapy targets, making it valuable for investigating fundamental tumor immunology.
Assuntos
Antígenos , Receptores de Antígenos de Linfócitos T , Humanos , Ligantes , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Peptídeos , Complexo Principal de HistocompatibilidadeRESUMO
DNA damage contributes to the aging of hematopoietic stem cells (HSCs), yet the underlying molecular mechanisms are not fully understood. In this study, we identified a heterogeneous functional role of microcephalin (MCPH1) in the nucleus and cytoplasm of mouse HSCs. In the nucleus, MCPH1 maintains genomic stability, whereas in the cytoplasm, it prevents necroptosis by binding with p-RIPK3. Aging triggers MCPH1 translocation from cytosol to nucleus, reducing its cytoplasmic retention and leading to the activation of necroptosis and deterioration of HSC function. Mechanistically, we found that KAT7-mediated lysine acetylation within the NLS motif of MCPH1 in response to DNA damage facilitates its nuclear translocation. Targeted mutation of these lysines inhibits MCPH1 translocation and, consequently, compromises necroptosis. The dysfunction of necroptosis signaling, in turn, improves the function of aged HSCs. In summary, our findings demonstrate that DNA damage-induced redistribution of MCPH1 promotes HSC aging and could have broader implications for aging and aging-related diseases.
Assuntos
Dano ao DNA , Necroptose , Animais , Camundongos , Envelhecimento/genética , Dano ao DNA/genética , Instabilidade Genômica , Células-Tronco Hematopoéticas/fisiologia , Translocação GenéticaRESUMO
Polycyclic aromatic hydrocarbons are a persistent organic pollutant, and their biodegradation in the soil is often limited due to the limited degradation ability of indigenous bacteria and the low activity of exogenous PAH degrading bacteria. Immobilized microbial technology can protect microorganisms from the impact of harsh environments, and distiller's grains have the potential as carriers for microbial immobilization. This study aims to use distiller's grains as a microbial carrier, investigate the feasibility of immobilized microorganisms using distiller's grains for remediation of PAH contaminated soil; explore the relationship between soil nutrient content, consumption, and PAH degradation rate; and reveal the mechanism of bioremediation from the perspective of soil enzyme activity and microbial community composition. The results showed that after 72 days of remediation, the removal rates of phenanthrene and pyrene in the treatment of immobilized microorganisms in distiller grains reached 91.78% and 58.59%, respectively. Distiller grains can serve as a carrier for microorganisms, providing them with shelter and nutrients to enhance their chance of survival. Additionally, they can regulate the composition of soil particles and improve aeration, thereby increasing the efficiency of PAH degradation in soil.
Assuntos
Microbiota , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo , Poluentes do Solo/análise , Microbiologia do SoloRESUMO
Gut microbiota are associated with adverse neurodevelopmental outcomes in preterm infants; however, the precise causal relationship remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to comprehensively study the relationship between gut microbiota and adverse neurodevelopmental outcomes in preterm infants and identify specific causal bacteria that may be associated with the occurrence and development of adverse neurodevelopmental outcomes in preterm infants. The genome-wide association analysis (GWAS) of the MiBioGen biogroup was used as the exposure data. The GWAS of six common adverse neurodevelopmental outcomes in premature infants from the FinnGen consortium R9 was used as the outcome data. Genetic variations, namely, single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and genome-wide statistical significance threshold (5 × 10-8) were selected as instrumental variables (IVs). MR studies use inverse variance weighting (IVW) as the main method. To supplement this, we also applied three additional MR methods: MR-Egger, weighted median, and weighted mode. In addition, the Cochrane's Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods were used for sensitivity analysis. Our study shows a causal relationship between specific gut microbiota and neurodevelopmental outcomes in preterm infants. These findings provide new insights into the mechanism by which gut microbiota may mediate adverse neurodevelopmental outcomes in preterm infants.
RESUMO
Aims: White matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia. Main methods: We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups. Key findings: Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7. Significance: Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.
RESUMO
Fluorescent organic nanoparticles (NPs) with exceptional brightness hold significant promise for demanding fluorescence bioimaging applications. Although considerable efforts are invested in developing novel organic dyes with enhanced performance, augmenting the brightness of conventional fluorophores is still one of the biggest challenges to overcome. This study presents a supramolecular strategy for constructing ultrabright fluorescent nanoparticles in aqueous media (referred to as "Supra-fluorophores") derived from conventional fluorophores. To achieve this, this course has employed a cylindrical nanoparticle with a hydrophobic microdomain, assembled by a cyclic peptide-diblock copolymer conjugate in water, as a supramolecular scaffold. The noncovalent dispersion of fluorophore moieties within the hydrophobic microdomain of the scaffold effectively mitigates the undesired aggregation-caused quenching and fluorescence quenching by water, resulting in fluorescent NPs with high brightness. This strategy is applicable to a broad spectrum of fluorophore families, covering polyaromatic hydrocarbons, coumarins, boron-dipyrromethenes, cyanines, xanthenes, and squaraines. The resulting fluorescent NPs demonstrate high fluorescence quantum yield (>30%) and brightness per volume (as high as 12 060 m-1 cm-1 nm-3). Moreover, high-performance NPs with emission in the NIR region are constructed, showcasing up to 20-fold increase in both brightness and photostability. This Supra-fluorophore strategy offers a versatile and effective method for transforming existing fluorophores into ultrabright fluorescent NPs in aqueous environments, for applications such as bioimaging.
RESUMO
Lignin is a complex biopolymer formed through the condensation of three monomeric precursors known as monolignols. However, the mechanism underlying lignin precursor transport remains elusive, with uncertainty over whether it occurs through passive diffusion or an active energized process. ATP-binding cassette 36 (ABCG36) plays important roles in abiotic stress resistance. In this study, we investigated the transport functions of LkABCG36 (Larix kaempferi) for lignin precursors and the potential effects of LkABCG36 overexpression in plants. LkABCG36 enhanced the ability of tobacco (Nicotiana tabacum) bright yellow-2 (BY-2) cells to resist monolignol alcohol stress. Furthermore, LkABCG36 overexpression promoted lignin deposition in tobacco plant stem tissue. To understand the underlying mechanism, we measured the BY-2 cell ability to export lignin monomers and the uptake of monolignol precursors in inside-out (inverted) plasma membrane vesicles. We found that the transport of coniferyl and sinapyl alcohols is an ATP-dependent process. Our data suggest that LkABCG36 contributes to lignin accumulation in tobacco stem tissues through a mechanism involving the active transport of lignin precursors to the cell wall. These findings shed light on the lignin biosynthesis process, with important implications for enhancing lignin deposition in plants, potentially leading to improved stress tolerance and biomass production.
Assuntos
Lignina , Proteínas de Membrana Transportadoras , Lignina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Transporte Biológico , Parede Celular/metabolismo , Plantas/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
The plant-specific WRKY transcription factor family members have diverse regulatory effects on the genes associated with many plant processes. Although the WRKY proteins in Arabidopsis thaliana and other species have been thoroughly investigated, there has been relatively little research on the WRKY family in Luffa cylindrica, which is one of the most widely grown vegetables in China. In this study, we performed a genome-wide analysis to identify L. cylindrica WRKY genes, which were subsequently classified and examined in terms of their gene structures, chromosomal locations, promoter cis-acting elements, and responses to abiotic stress. A total of 62 LcWRKY genes (471-2238 bp) were identified and divided into three phylogenetic groups (I, II, and III), with group II further divided into five subgroups (IIa, IIb, IIc, IId, and IIe) in accordance with the classification in other plants. The LcWRKY genes were unevenly distributed across 13 chromosomes. The gene structure analysis indicated that the LcWRKY genes contained 0-11 introns (average of 4.4). Moreover, 20 motifs were detected in the LcWRKY proteins with conserved motifs among the different phylogenetic groups. Two subgroup IIc members (LcWRKY16 and LcWRKY31) contained the WRKY sequence variant WRKYGKK. Additionally, nine cis-acting elements related to diverse responses to environmental stimuli were identified in the LcWRKY promoters. The subcellular localization analysis indicated that three LcWRKY proteins (LcWRKY43, LcWRKY7, and LcWRKY23) are localized in the nucleus. The tissue-specific LcWRKY expression profiles reflected the diversity in LcWRKY expression. The RNA-seq data revealed the effects of low-temperature stress on LcWRKY expression. The cold-induced changes in expression were verified via a qRT-PCR analysis of 24 differentially expressed WRKY genes. Both LcWRKY7 and LcWRKY12 were highly responsive to the low-temperature treatment (approximately 110-fold increase in expression). Furthermore, the LcWRKY8, LcWRKY12, and LcWRKY59 expression levels increased by more than 25-fold under cold conditions. Our findings will help clarify the evolution of the luffa WRKY family while also providing valuable insights for future studies on WRKY functions.
RESUMO
BACKGROUND: Pulmonary premetastatic niche (PMN) formation plays a key role in the lung metastasis of hepatocellular carcinoma (HCC). Hypoxia promotes the secretion of tumor-derived exosomes (TDEs) and facilitates the formation of PMN. However, the mechanisms remain unexplored. METHODS: TDEs from normoxic (N-TDEs) or hypoxic (H-TDEs) HCC cells were used to induce fibroblast activation in vitro and PMN formation in vivo. Oleanolic acid (OA) was intragastrically administered to TDEs-preconditioned mice. Bioinformatics analysis and drug affinity responsive target stability (DARTS) assays were performed to identify targets of OA in fibroblasts. RESULTS: H-TDEs induced activation of pulmonary fibroblasts, promoted formation of pulmonary PMN and subsequently facilitated lung metastasis of HCC. OA inhibited TDEs-induced PMN formation and lung metastasis and suppressed TDEs-mediated fibroblast activation. MAPK1 and MAPK3 (ERK1/2) were the potential targets of OA. Furthermore, H-TDEs enhanced ERK1/2 phosphorylation in fibroblasts in vitro and in vivo, which was suppressed by OA treatment. Blocking ERK1/2 signaling with its inhibitor abated H-TDEs-induced activation of fibroblasts and PMN formation. H-TDEs-induced phosphorylation of ERK1/2 in fibroblasts touched off the activation NF-κB p65, which was mitigated by OA. In addition, the ERK activator C16-PAF recovered the activation of ERK1/2 and NF-κB p65 in H-TDEs-stimulated MRC5 cells upon OA treatment. CONCLUSION: The present study offers insights into the prevention of TDEs-induced PMN, which has been insufficiently investigated. OA suppresses the activation of inflammatory fibroblasts and the development of pulmonary PMN by targeting ERK1/2 and thereby has therapeutic potential in the prevention of lung metastasis of HCC.
Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , Neoplasias Pulmonares , Ácido Oleanólico , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Ácido Oleanólico/metabolismo , NF-kappa B/metabolismo , Sistema de Sinalização das MAP Quinases , Exossomos/metabolismo , Hipóxia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismoRESUMO
BACKGROUND: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. OBJECTIVE: To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, in vivo experiments were carried out further to validate the therapeutic effects of XCHD on psoriasis. RESULTS: 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. CONCLUSION: XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.
Assuntos
Medicamentos de Ervas Chinesas , Psoríase , Animais , Camundongos , Farmacologia em Rede , Simulação de Acoplamento Molecular , Pele , Inflamação , Medicina Tradicional ChinesaRESUMO
Melanoma is the most lethal type of skin cancer with an increasing cutaneous cancerrelated mortality rate worldwide. Despite therapeutic advances in targeted therapy and immunotherapy, the overall survival of patients with melanoma remains unsatisfactory. Thus, a further understanding of the pathogenesis of melanoma may aid towards the development of therapeutic strategies. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a key enzyme that converts lysophosphatidylcholine into phosphatidylcholine in lipid remodeling. In the present study, LPCAT1 was found to play a proproliferative role in melanoma. Firstly, the expression of LPCAT1 was found to be upregulated in tissues from patients with melanoma compared with that in benign nevi. Subsequently, LPCAT1 knockdown was performed, utilizing short hairpin RNA, which induced melanoma cell cycle arrest at the G1/S transition and promoted cell death. Moreover, LPCAT1 facilitated melanoma cell growth in an Aktdependent manner. In summary, the results of the present study indicate that targeting LPCAT1 may impede cell proliferation by inhibiting Akt signaling, thus providing a promising therapeutic strategy for melanoma in clinical practice.
Assuntos
1-Acilglicerofosfocolina O-Aciltransferase , Melanoma , Proteínas Proto-Oncogênicas c-akt , Neoplasias Cutâneas , Humanos , 1-Acilglicerofosfocolina O-Aciltransferase/genética , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
Introduction: Bacterial biofilm is a well-known characteristic that plays important roles in diverse physiological functions, whereas the current intrinsic regulatory mechanism of its formation is still largely unknown. Methods: In the present study, a label-free based quantitative proteomics technology was conducted to compare the differentially expressed proteins (DEPs) between ΔuidR and the wild-type strain in the biofilm state. Results: The results showed that the deletion of gene uidR encoding a TetR transcriptional regulator significantly increased the biofilm formation in Aeromonas hydrophila. And there was a total of 220 DEPs, including 120 up-regulated proteins and 100 down-regulated proteins between ΔuidR and the wild-type strain based on the quantitative proteomics. Bioinformatics analysis suggested that uidR may affect bacterial biofilm formation by regulating some related proteins in glyoxylic acid and dicarboxylic acid pathway. The expressions of selected proteins involved in this pathway were further confirmed by q-PCR assay, and the results was in accordance with the quantitative proteomics data. Moreover, the deletion of four genes (AHA_3063, AHA_3062, AHA_4140 and aceB) related to the glyoxylic acid and dicarboxylic acid pathway lead to a significant decrease in the biofilm formation. Discussion: Thus, the results indicated that uidR involved in the regulatory of bacterial biofilm formation, and it may provide a potential target for the drug development and a new clue for the prevention of pathogenic A. hydrophila in the future.