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Hollow structures are essential for development and physiological activity. The construction and maintenance of hollow structures never cease throughout the lives of multicellular animals. Epithelial tissue closure is the main strategy used by living organisms to build hollow structures. The high diversity of hollow structures and the simplicity of their development in Drosophila make it an excellent model for the study of hollow structure morphogenesis. In this review, we summarize the tissue closure processes in Drosophila that give rise to or maintain hollow structures and highlight the molecular mechanisms and distinct cell biology involved in these processes.
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Vacancy-ordered perovskites and derivatives represent an important subclass of hybrid metal halides with promise in applications including light emitting devices and photovoltaics. Understanding the vacancy-property relationship is crucial for designing related task-specific materials, yet research in this field remains sporadic. For the first time, we use the Connolly surface to quantitatively calculate the volume of vacancy (Vâ¡, â¡ = vacancy) in vacancy-ordered double perovskite derivatives (VDPDs). A relationship between void fraction and the structure, photoluminescent properties and humidity stability was established based on zero-dimensional (0-D) [N(alkyl)4]2Sbâ¡Cl5â¡'-type VDPDs. Compared with the more commonly studied A2M(IV)X6â¡-type double perovskite (A = cation, M = metal ion, X = halide), [N(alkyl)4]2Sbâ¡Cl5â¡' features double vacancy sites. Our results demonstrate an inverse relationship between the photoluminescent quantum yield and Vâ¡ in 0-D VDPDs. Additionally, structural transformation from A2SbCl5 to A3Sb2Cl9 was first reported, during which the novel 'gate-opening' gas adsorption phenomenon was observed in VDPDs for the first time, as evidenced by 'S'-shaped sorption isotherms for water vapor, indicating a cation-controlled water-vapor response behavior. A mixed-cation strategy was developed to modulate the humidity stability of VDPDs. Characterized by controllable water-responsive behavior and unique 'on-off-on' luminescent switching, A2M(III)â¡X5â¡'-type materials show great promise for multi-level information anti-counterfeiting applications.
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OBJECTIVES: In the fall-winter of 2023, China experienced its first epidemic season of respiratory diseases since the COVID-19 pandemic. Gathering timely data about pathogenetic characteristics of respiratory infections is crucial to complement current respiratory surveillance mechanisms in China. Data from direct-to-consumer (DTC) multi-respiratory pathogen (MRP) testing could serve as a novel source of multi-pathogen data for community-based surveillance. METHODS: A pioneering initiative was launched to detect multiple respiratory pathogens in Beijing and Guangzhou, China. DTC MRP tests were used to provide proactive surveillance ahead of medical services. RESULTS: A total of 28,018 participants were enrolled between 22 August and 10 December 2023. Positive findings for at least one respiratory pathogen were observed in 26,202 (93.5%) participants. Influenza virus A, respiratory syncytial virus (RSV), and human adenovirus are the three leading viral pathogens detected with proportions of 18.0%, 10.6%, and 8.8%. Viral-bacterial pathogens were co-detected in 9736 (34.7%) of participants, which reduced to 22.2% for bacterial-bacterial co-detection, and 22.0% for bacterial mono-detection. The epidemiological ecology of respiratory pathogens within both viral clusters and specific pathogens varied among cities. The peak of RSV epidemics in Guangzhou occurred in the fall of 2023, earlier than in Beijing. CONCLUSION: The innovative program offered enhanced surveillance capabilities beyond traditional methods, enabling prompt feedback about test results and mitigating the risk of cross-infection caused by waits in healthcare facilities.
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The efficacy of vitamin C in age-related hearing loss, i.e., presbycusis, remains debatable. On a separate note, inflammation induced by the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is involved in the progression of presbycusis. In this study, we investigated the effect of vitamin C on male C57BL/6 mice's presbycusis and NLRP3 inflammasome. The results showed that vitamin C treatment improved hearing, reduced the production of inflammatory factors, inhibited NLRP3 inflammasome activation, and decreased cytosolic mitochondrial DNA (mtDNA) in the C57BL/6 mouse cochlea, inferior colliculus, and auditory cortex. According to this study, vitamin C protects auditory function in male C57BL/6 presbycusis mice through reducing mtDNA release, inhibiting the NLRP3 inflammasome activation in the auditory pathway. Our study provides a theoretical basis for applying vitamin C to treat presbycusis.
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Ácido Ascórbico , DNA Mitocondrial , Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Presbiacusia , Animais , Masculino , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Ácido Ascórbico/administração & dosagem , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Presbiacusia/metabolismo , Presbiacusia/prevenção & controle , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , DNA Mitocondrial/metabolismo , DNA Mitocondrial/efeitos dos fármacos , Camundongos , Cóclea/efeitos dos fármacos , Cóclea/metabolismo , Córtex Auditivo/efeitos dos fármacos , Córtex Auditivo/metabolismoRESUMO
BACKGROUND: The limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach. METHODS: We utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis. RESULTS: The scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition. CONCLUSIONS: This study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process.
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Astrócitos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Reprogramação Celular , Proteínas do Tecido Nervoso , Fator de Transcrição PAX6 , Análise de Célula Única , Astrócitos/metabolismo , Animais , Reprogramação Celular/genética , Fator de Transcrição PAX6/genética , Fator de Transcrição PAX6/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Análise de Célula Única/métodos , Camundongos , Diferenciação Celular/genética , Linhagem da Célula/genética , Neurônios/metabolismo , Células CultivadasRESUMO
MicroRNA (miRNA) represents a class of important potential biomarkers, and their intracellular imaging is extremely useful for fundamental research and early diagnosis of human cancers. Hybridization chain reaction (HCR) has been shown to be effective in detecting miRNA in living cells. However, its practical applications are still hampered by inefficient reaction kinetics and poor biological stability under complex intracellular conditions. To address these issues, we report a palindrome-mediated multiple hybridization chain reaction (P-HCR) system to better visualize intracellular miRNAs. In the presence of the target miRNA, a layered nanosheet DNA architecture (LSDA) can be assembled in situ via the palindrome-mediated multiple HCR process. We demonstrate that the biological stability of this reaction system could be significantly improved by designing the probes to dumbbell-shaped structures and the distance of hairpins was effectively decreased due to palindrome-chained effect. Consequently, miRNA can be quantitatively identified even at extremely low concentrations of 4.7 pM. The P-HCR system can effectively differentiate the expression levels of miRNA in different tumor cells and normal cells, as demonstrated in live cell tests and the results were in agreement with the PCR, which is considered the gold standard. The new (P-HCR) system has the potential to revolutionize miRNA imaging in living cells.
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DNA , MicroRNAs , Nanoestruturas , Hibridização de Ácido Nucleico , MicroRNAs/análise , Humanos , Nanoestruturas/química , DNA/química , Sondas de DNA/química , Sequências Repetidas InvertidasRESUMO
Objective: To explore the symptom experiences and influencing factors of gastrointestinal (GI) cancer patients on chemotherapy (CTX) in China. Methods: Semi-structured interviews were conducted with 13 GI cancer patients undergoing CTX. Following the Colaizzi 7-step analysis method, the interview data were read carefully, meaningful statements related to the research questions were extracted, coded, collected, and described in detail, and the authenticity of the theme was verified. Results: Nine themes were grouped into two main areas including the characteristics of symptom experiences and influences on symptom experiences. Conclusion: The symptom experiences of patients undergoing CTX for GI cancer is poor and influenced by multiple factors. Nurses need to pay attention to the assessment and monitoring of CTX-related symptoms, improve symptom recognition, enhance doctor-patient communication and social support, explore intelligent management methods, and increase the efficiency of healthcare services to improve patients' symptom experience.
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When magnetic matching aided navigation is applied to an underwater vehicle, the magnetometer must be installed inside the vehicle, considering the navigation safety and concealment of the underwater vehicle. Then, the interference magnetic field will seriously affect the accuracy of geomagnetic field measurement, which directly affects the accuracy of geomagnetic matching aided navigation. Therefore, improving the accuracy of geomagnetic measurements inside the vehicle through error compensation has become one of the most difficult problems that requires an urgent solution in geomagnetic matching aided navigation. In order to solve this problem, this paper establishes the calculation model of the internal magnetic field of the underwater vehicle and the geomagnetic measurement error model of the ship-borne magnetometer. Then, a compensation method for the geomagnetic measurement error of the ship-borne magnetometer, based on the constrained total least square method, is proposed. To verify the effectiveness of the method proposed in this paper, a simulation experiment of geomagnetic measurement and compensation of a ship-borne three-axis magnetometer was constructed. Among them, to be closer to the real situation, a combination of the geomagnetism model, the elliptic shell model and the magnetic dipole model was used to simulate the internal magnetic field of the underwater vehicle. The experimental results indicated that the root mean square error of geomagnetic measurement in an underwater vehicle was less than 5 nT after compensation, and the accuracy of geomagnetic measurement met the requirements of geomagnetic matching aided navigation.
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ETHNOPHARMACOLOGICAL RELEVANCE: Initial investigative research indicated that the essential oil from Chimonanthus nitens Oliv. Leaves (CLO) significantly reduces lung tissues inflammation and effectively repairs Acute lung injury (ALI) mice model. However, the mechanism underlying is not clear, and the impacts of CLO on oxidative stress require further investigation. AIM OF THE STUDY: The purpose of the experiment was to validate the influence of CLO in ALI model mice, as well as its potential mechanisms. MATERIALS AND METHODS: Lipopolysaccharide-induced establishment of the A549 cell inflammation model, and ALI mice model was established by intrathecal administration of LPS. RESULTS: CLO significantly reduced the release of inflammatory cytokines in A549 cells, lowered MDA and ROS levels, and enhanced SOD activity. Animal experiment results showed that CLO dramatically decreased white blood cell count, the expression of inflammatory cytokines, and the destruction of alveolar structures. CLO enhances the activity of antioxidant enzymes. Western Blot and q-PCR analyses have revealed that the mechanism of CLO is correlation with the NF-κB and Nrf2 signaling pathways in cellular and animal models. Pathway inhibitor experiments indicated that there might be functional crosstalk between these two pathways. CONCLUSIONS: CLO may regulate inflammation and oxidative stress in LPS-induced ALI through NF-κB and Nrf2 signaling pathways. This finding could be novel in the pharmacological treatment of ALI.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Óleos Voláteis , Estresse Oxidativo , Folhas de Planta , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Células A549 , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Calycanthaceae/química , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Highly selective capture of radiocesium is an urgent need for environmental radioactive contamination remediation and spent fuel disposal. Herein, a strategy is proposed for construction of "inorganic ion-imprinted adsorbents" with ion recognition-separation capabilities, and a metal sulfide Cs2.33Ga2.33Sn1.67S8·H2O (FJSM-CGTS) with "imprinting effect" on Cs+ is prepared. We show that the K+ activation product of FJSM-CGTS, Cs0.51K1.82Ga2.33Sn1.67S8·H2O (FJMS-KCGTS), can reach adsorption equilibrium for Cs+ within 5 min, with a maximum adsorption capacity of 246.65 mg·g-1. FJMS-KCGTS overcomes the hindrance of Cs+ adsorption by competing ions and realizes highly selective capture of Cs+ in complex environments. It shows successful cleanup for actual 137Cs-liquid-wastes generated during industrial production with removal rates of over 99%. Ion-exchange column filled with FJMS-KCGTS can efficiently treat 540 mL Cs+-containing solutions (31.995 mg·L-1) and generates only 0.12 mL of solid waste, which enables waste solution volume reduction. Single-crystal structural analysis and density functional theory calculations are used to visualize the "ion-imprinting" process and confirm that the "imprinting effect" originates from the spatially confined effect of the framework. This work clearly reveals radiocesium capture mechanism and structure-function relationships that could inspire the development of efficient inorganic adsorbents for selective recognition and separation of key radionuclides.
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Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.
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Canagliflozina , Proliferação de Células , Hipertensão Pulmonar , Estresse Oxidativo , PPAR gama , Animais , Masculino , Camundongos , Ratos , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , PPAR gama/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos , Serina/química , Serina/metabolismoRESUMO
We attempted to investigate the role of HOXB7 in tumor progression and evolution by means of an extensive computer screening analysis of various cancer types. We performed univariate Cox regression and Kaplan-Meier survival analyses to assess the impact of HOXB7 on overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in different types of cancer. Furthermore, we examined the relationship between HOXB7 and several clinical features: tumor microenvironment, immune regulatory genes, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI). We performed gene set enrichment analysis to gain deeper insights into the potential molecular mechanisms of HOXB7, and validated our findings through functional assays in cells, including methyl thiazolyl tetrazolium cytotoxicity and Transwell invasion assays. HOXB7 expression was associated with different clinical characteristics in numerous malignancies. Higher HOXB7 expression was associated with worse OS, DSS, and PFI in some cancer types. In particular, HOXB7 expression was favorably associated with immune cell infiltration, immune regulatory genes, immunological checkpoints, TMB, and MSI in malignancies. Furthermore, we identified a strong link between copper death-associated gene expression and HOXB7 expression. According to the findings of this study, HOXB7 might serve as an appealing focus for tumor diagnosis and immunotherapy and a prospective indicator of prognosis.
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Biomarcadores Tumorais , Proteínas de Homeodomínio , Neoplasias , Humanos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Prognóstico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.
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Medicamentos de Ervas Chinesas , Metabolismo Energético , Alvo Mecanístico do Complexo 1 de Rapamicina , Mitocôndrias , Panax notoginseng , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Panax notoginseng/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Metabolismo Energético/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Rizoma/química , Humanos , Transdução de Sinais/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/metabolismoRESUMO
Antimony sulfide (Sb2S3) has a high theoretical specific capacity due to its two reaction mechanisms of conversion and alloying during the Li+-(de)intercalation process, thus becoming a promising lithium-ion battery (LIB) anode material. However, its poor inherent conductivity and large volume expansion during repeated Li+-(de)intercalation processes greatly hinder the in-depth development of Sb2S3 based LIB anode materials. Herein, an Sb2S3/SnO2@rGO composite was prepared by using an interface engineering technique involving metal-containing ionic liquid precursors, in which Sb2S3/SnO2 quantum dots (QDs) as p-n heterojunctions are uniformly anchored on the surface of reduced graphene oxide (rGO). The p-n heterogeneous interface between Sb2S3 and SnO2 QDs induces an internal electric field, promoting the electronic/ion transport during electrochemical reactions, and the QD-sized Sb2S3/SnO2 heterostructure with a larger surface area provides more active sites for Li+-(de)intercalation reactions. In addition, the rGO matrix acts as a buffer to prevent the aggregation of active Sb2S3 and SnO2 QDs, alleviate the volume expansion, and enhance the conductivity of the composite during repeated cycles. These advantages endow the designed Sb2S3/SnO2@rGO electrode with excellent reaction kinetics and good long cycling stability. As an anode material of LIBs, it can still provide a reversible specific capacity of 474 mA h g-1 after 2000 cycles at a high current density of 3.0 A g-1, which is superior to those of most of the previously reported Sb2S3-based carbon materials. The p-n heterostructure construction strategy of nano-metal sulfide/metal oxides in this work can provide inspiration for the design and synthesis of other advanced energy storage materials.
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AIMS: Acute lung injury (ALI) is a life-threatening lung disease characterized by inflammatory cell infiltration and lung epithelial injury. Icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exhibits anti-inflammatory and immunomodulatory effects. However, the effect and mechanism of ICS II in ALI remain unclear. The purpose of the current study was to investigate the pharmacological effect and underlying mechanism of ICS II in ALI. MAIN METHODS: Models of neutrophil-like cells, human peripheral blood neutrophils, and lipopolysaccharide (LPS)-induced ALI mouse model were utilized. RT-qPCR and Western blotting determined the gene and protein expression levels. Protein distribution and quantification were analyzed by immunofluorescence. KEY FINDINGS: ICS II significantly reduced lung histopathological damage, edema, and inflammatory cell infiltration, and it reduced pro-inflammatory cytokines in ALI. There is an excessive activation of neutrophils leading to a significant production of NETs in ALI mice, a process mitigated by the administration of ICS II. In vivo and in vitro studies found that ICS II could decrease NET formation by targeting neutrophil C-X-C chemokine receptor type 4 (CXCR4). Further data showed that ICS II reduces the overproduction of dsDNA, a NETs-related component, thereby suppressing cGAS/STING/NF-κB signalling pathway activation and inflammatory mediators release in lung epithelial cells. SIGNIFICANCE: This study suggested that ICS II may alleviate LPS-induced ALI by modulating the inflammatory response, indicating its potential as a therapeutic agent for ALI treatment.
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Lesão Pulmonar Aguda , Armadilhas Extracelulares , Flavonoides , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Neutrófilos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/imunologia , Animais , Camundongos , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/imunologia , Flavonoides/farmacologia , Masculino , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Anti-Inflamatórios/farmacologiaRESUMO
Stroke is a leading cause of death and disability, and genetic risk factors play a significant role in its development. Unfortunately, effective therapies for stroke are currently limited. Early detection and diagnosis are critical for improving outcomes and developing new treatment strategies. In this study, we aimed to identify potential biomarkers and effective prevention and treatment strategies for stroke by conducting transcriptome and single-cell analyses. Our analysis included screening for biomarkers, functional enrichment analysis, immune infiltration, cell-cell communication, and single-cell metabolism. Through differential expression analysis, enrichment analysis, and protein-protein interaction (PPI) network construction, we identified HIST2H2AC as a potential biomarker for stroke. Our study also highlighted the diagnostic role of HIST2H2AC in stroke, its relationship with immune cells in the stroke environment, and our improved understanding of metabolic pathways after stroke. Overall, our research provided important insights into the pathogenesis of stroke, including potential biomarkers and treatment strategies that can be explored further to improve outcomes for stroke patients.
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Biomarcadores , Histonas , Acidente Vascular Cerebral , Humanos , Biomarcadores/análise , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas , Análise de Célula Única , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/metabolismo , Transcriptoma , Histonas/análiseRESUMO
Noncoding RNAs have been shown to play essential roles in hypoxic pulmonary hypertension (HPH). Our preliminary data showed that HPH is attenuated by fibroblast growth factor 21 (FGF21) administration. Therefore, we further investigated the whole transcriptome RNA expression patterns and interactions in a mice HPH model treated with FGF21. By whole-transcriptome sequencing, differentially expressed mRNAs, miRNAs, lncRNAs, and circRNAs were successfully identified in normoxia (Nx) vs. hypoxia (Hx) and Hx vs. hypoxia + FGF21 (Hx + F21). Differentially expressed mRNAs, miRNAs, lncRNAs, and circRNAs regulated by hypoxia and FGF21 were selected through intersection analysis. Based on prediction databases and sequencing data, differentially co-expressed mRNAs, miRNAs, lncRNAs, and circRNAs were further screened, followed by functional enrichment analysis. MAPK signaling pathway and epigenetic modification were enriched and may play fundamental roles in the therapeutic effects of FGF21. The ceRNA regulatory network of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA was constructed with miR-7a-5p, miR-449c-5p, miR-676-3p and miR-674-3p as the core. In addition, quantitative real-time PCR experiments were employed to verify the whole-transcriptome sequencing data. The results of luciferase reporter assays highlighted the relationship between miR-449c-5p and XR_878320.1, miR-449c-5p and Stab2, miR-449c-5p and circ_mtcp1, which suggesting that miR-449c-5p may be a key regulator of FGF21 in the treatment of PH. Taken together, this study provides potential biomarkers, pathways, and ceRNA regulatory networks in HPH treated with FGF21 and will provide an experimental basis for the clinical application of FGF21 in PH.
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Fatores de Crescimento de Fibroblastos , Hipertensão Pulmonar , RNA Endógeno Competitivo , Animais , Humanos , Masculino , Camundongos , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/uso terapêutico , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/genética , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RNA Circular/genética , RNA Endógeno Competitivo/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , TranscriptomaRESUMO
Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.
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BACKGROUND: The precise origin of newly formed ACTA2+ (alpha smooth muscle actin-positive) cells appearing in nonmuscularized vessels in the context of pulmonary hypertension is still debatable although it is believed that they predominantly derive from preexisting vascular smooth muscle cells (VSMCs). METHODS: Gli1Cre-ERT2; tdTomatoflox mice were used to lineage trace GLI1+ (glioma-associated oncogene homolog 1-positive) cells in the context of pulmonary hypertension using 2 independent models of vascular remodeling and reverse remodeling: hypoxia and cigarette smoke exposure. Hemodynamic measurements, right ventricular hypertrophy assessment, flow cytometry, and histological analysis of thick lung sections followed by state-of-the-art 3-dimensional reconstruction and quantification using Imaris software were used to investigate the contribution of GLI1+ cells to neomuscularization of the pulmonary vasculature. RESULTS: The data show that GLI1+ cells are abundant around distal, nonmuscularized vessels during steady state, and this lineage contributes to around 50% of newly formed ACTA2+ cells around these normally nonmuscularized vessels. During reverse remodeling, cells derived from the GLI1+ lineage are largely cleared in parallel to the reversal of muscularization. Partial ablation of GLI1+ cells greatly prevented vascular remodeling in response to hypoxia and attenuated the increase in right ventricular systolic pressure and right heart hypertrophy. Single-cell RNA sequencing on sorted lineage-labeled GLI1+ cells revealed an Acta2high fraction of cells with pathways in cancer and MAPK (mitogen-activated protein kinase) signaling as potential players in reprogramming these cells during vascular remodeling. Analysis of human lung-derived material suggests that GLI1 signaling is overactivated in both group 1 and group 3 pulmonary hypertension and can promote proliferation and myogenic differentiation. CONCLUSIONS: Our data highlight GLI1+ cells as an alternative cellular source of VSMCs in pulmonary hypertension and suggest that these cells and the associated signaling pathways represent an important therapeutic target for further studies.
Assuntos
Hipertensão Pulmonar , Remodelação Vascular , Proteína GLI1 em Dedos de Zinco , Animais , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Camundongos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Camundongos Endogâmicos C57BL , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Camundongos Transgênicos , Masculino , Humanos , Hipóxia/metabolismo , Hipóxia/fisiopatologiaRESUMO
Essential oils (EO), secondary metabolites of plants are fragrant oily liquids with antibacterial, antiviral, anti-inflammatory, anti-allergic, and antioxidant effects. They are widely applied in food, medicine, cosmetics, and other fields. However, the quality of EOs remain uncertain owing to their high volatility and susceptibility to oxidation, influenced by factors such as the harvesting season, extraction, and separation techniques. Additionally, the huge economic value of EOs has led to a market marked by widespread and varied adulteration, making the assessment of their quality challenging. Therefore, developing simple, quick, and effective identification techniques for EOs is essential. This review comprehensively summarizes the techniques for assessing EO quality and identifying adulteration. It covers sensory evaluation, physical and chemical property evaluation, and chemical composition analysis, which are widely used and of great significance for the quality evaluation and adulteration detection of EOs.