RESUMO
Sepsis is a severe inflammatory disease characterized by cytokine storm, often accompanied by disseminated intravascular coagulation (DIC). PANoptosis is a novel form of cell death triggered by cytokine storms, characterized by a cascade reaction of pyroptosis, apoptosis, and necroptosis. It exists in septic platelets and is closely associated with the onset and progression of DIC. However, there remains an unmet need for drugs targeting PANoptosis. The anti-PANoptosis effect of myricetin was predicted using network pharmacology and confirmed through molecular docking. In vitro platelet activation models demonstrated that myricetin significantly attenuated platelet particle release, integrin activation, adhesion, spreading, clot retraction, and aggregation. Moreover, in a sepsis model, myricetin reduced inflammatory infiltration in lung tissue and platelet activation while improving DIC. Additionally, whole blood sequencing samples from sepsis patients and healthy individuals were analyzed to elucidate the up-regulation of the PANoptosis targets. Our findings demonstrate the inhibitory effect of myricetin on septic platelet PANoptosis, indicating its potential as a novel anti-cellular PANoptosis candidate and therapeutic agent for septic DIC. Furthermore, our study establishes a foundation for utilizing network pharmacology in the discovery of new drugs to treat various diseases.
Assuntos
Plaquetas , Coagulação Intravascular Disseminada , Flavonoides , Sepse , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Sepse/tratamento farmacológico , Sepse/sangue , Humanos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/patologia , Coagulação Intravascular Disseminada/sangue , Animais , Masculino , Simulação de Acoplamento Molecular , Ativação Plaquetária/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos , Piroptose/efeitos dos fármacosRESUMO
A facile method was proposed for preparing controllable multicompartment gel microcarriers using an aqueous two-phase emulsion system. By leveraging the density difference between the upper polyethylene glycol solution and the lower dextran-calcium chloride (CaCl2) solution in the collection solution and the high viscosity of the lower solution, controllable fusion of core-shell droplets made by coextrusion devices was achieved at the water/water (w/w) interface to fabricate microcarriers with separated core compartments. By adjusting the sodium alginate concentration, collected solution composition, and number of fused liquid droplets, the pore size, shape, and number of compartments could be controlled. Caco-2 and HepG2 cells were encapsulated in different compartments to establish gut-liver coculture models, exhibiting higher viability and proliferation compared to monoculture models. Notably, significant differences in cytokine expression and functional proteins were observed between the coculture and monoculture models. This method provides new possibilities for preparing complex and functional three-dimensional coculture materials.
Assuntos
Alginatos , Técnicas de Cocultura , Emulsões , Humanos , Técnicas de Cocultura/métodos , Células Hep G2 , Emulsões/química , Células CACO-2 , Alginatos/química , Géis/química , Polietilenoglicóis/química , Cloreto de Cálcio/química , Dextranos/química , Proliferação de Células , Sobrevivência CelularRESUMO
Owing to stereoelectronic effects, lactones often deviate in reactivity from their open-chain ester analogues as demonstrated by the CH acidity (in DMSO) of 3-isochromanone (pKa = 18.8) and 2-coumaranone (pKa = 13.5), which is higher than that of ethyl phenylacetate (pKa = 22.6). We have now characterized the reactivity of the lactone enolates derived from 3-isochromanone and 2-coumaranone by following the kinetics of their Michael reactions with p-quinone methides and arylidenemalonates (reference electrophiles) in DMSO at 20 °C. Evaluation of the experimentally determined second-order rate constants k2 by the Mayr-Patz equation, lg k2 = sN(N + E), furnished the nucleophilicity parameters N (and sN) of the lactone enolates. By localizing their position on the Mayr nucleophilicity scale, the scope of their electrophilic reaction partners becomes predictable, and we demonstrate a novel catalytic methodology for a series of carbon-carbon bond-forming reactions of lactone enolates with chalcones under phase transfer conditions in toluene.
RESUMO
Three new ergosterol derivatives brassisterol A-C (1-3) and two new epimeric bicycle-lactones brassictones A and B (4 and 5), were isolated from the co-cultivation of Alternaria brassicicola and Penicillium granulatum. The absolute configurations of these isolates were confirmed by extensive NMR spectra, TD-DFT ECD calculation, and the single crystal XRD data analysis. Amongst the metabolites, compound 1 exhibited potential anti-Parkinson's disease activity in both MPTP-induced zebrafish and MPP+-induced SH-SY5Y cells. Molecular mechanism studies in vitro showed that 1 attenuated the increase of α-synuclein, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and GSDMD expression in the MPP+ induced PD model. Molecular docking in silico simulations exhibited that 1 was well accommodated to one of the binding pockets of NLRP3 8ETR in an appropriate conformation via forming typical hydrogen bonds as well as possessing a high negative binding affinity (-8.97 kcal/mol). Thus, our work suggested that 1 protected dopaminergic cell from neuroinflammation via targeting NLRP3/caspase-1/GSDMD signaling pathway.
Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Neuroblastoma , Animais , Humanos , Caspase 1/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Simulação de Acoplamento Molecular , Peixe-Zebra/metabolismo , Fungos/metabolismo , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de PorosRESUMO
Two pairs of enantiomers (1a-2b), namely (±)-alterpyrone F and (±)-alterpyrone G, along with a rare benzothiazole meroterpenoid granulathiazole A (3, GA), and two undescribed compounds called respectively granulahydeoate (4) and granulaone (5), were obtained from the co-cultivation of Alternaria brassicicola and Penicillium sp. HUBU0120. Exhaustive analyses of NMR, single crystal XRD, Mo2(OAc)4-induced circular dichroism data, and a modified Mosher's method distinguished the absolute configurations of isolates. Bioactive evaluations exhibited that GA possessed promising anti-PD activity in both in vitro and in vivo PD models viz. 6-OHDA-induced SH-SY5Y cells and 6-OHDA-induced zebrafish, respectively. Moreover, our research demonstrated that ferroptosis activated by 6-OHDA was mitigated in PD models after treated with GA. Extensive molecular mechanism studies in PD-modelled cells manifested that GA attenuated the decreased expressions of SLC7A11, GPX4, and FSP-1, and the increased level of ACSL4 via activating Nrf2/HO-1 pathway as well as ameliorated the accumulation of α-synuclein.
Assuntos
Ferroptose , Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Oxidopamina , Ferroptose/efeitos dos fármacos , Oxidopamina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Animais , Estrutura Molecular , Heme Oxigenase-1/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Peixe-Zebra , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/químicaRESUMO
Pulmonary fibrosis (PF) poses a significant challenge with limited treatment options and a high mortality rate of approximately 45 %. Qingkailing Granule (QKL), derived from the Angong Niuhuang Pill, shows promise in addressing pulmonary conditions. Using a comprehensive approach, combining network pharmacology analysis with experimental validation, this study explores the therapeutic effects and mechanisms of QKL against PF for the first time. In vivo, QKL reduced collagen deposition and suppressed proinflammatory cytokines in a bleomycin-induced PF mouse model. In vitro studies demonstrated QKL's efficacy in protecting cells from bleomycin-induced injury and reducing collagen accumulation and cell migration in TGF-ß1-induced pulmonary fibrosis cell models. Network pharmacology analysis revealed potential mechanisms, confirmed by western blotting, involving the modulation of PI3K/AKT and SRC/STAT3 signaling pathways. Molecular docking simulations highlighted interactions between QKL's active compounds and key proteins, showing inhibitory effects on epithelial damage and fibrosis. Collectively, these findings underscore the therapeutic potential of QKL in alleviating pulmonary inflammation and fibrosis through the downregulation of PI3K/AKT and SRC/STAT3 signaling pathways, with a pivotal role attributed to its active compounds.
Assuntos
Medicamentos de Ervas Chinesas , Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Transdução de Sinais , Colágeno/metabolismo , Colágeno/farmacologia , Colágeno/uso terapêutico , Fibrose , Bleomicina/efeitos adversosRESUMO
Vertically aligned carbon nanotubes array offers unique properties for various applications. Detaching them from the growth substrate, while preserving their vertical structure, is essential. Quartz, a cost-effective alternative to silicon wafers and metal-based substrates, can serve as both a reaction chamber and a growth substrate. However, the strong adhesive interaction with the quartz substrate remains an obstacle for further applications. Herein, we presented a simple and well-controlled exfoliation strategy assisted by the introduction of heteroatoms at root ends of a carbon nanotubes array. This strategy forms lower surface polarity of the carbon fragment to significantly reduce adhesion to the quartz substrate, which contributes to the effortless exfoliation. Furthermore, this scalable approach enables potential mass production on recyclable quartz substrates, enhancing the cost-effectiveness and efficiency. This work can establish a solid foundation for cost-competitive carbon nanotube-based technologies, offering a promising avenue for their widespread applications.
RESUMO
The hydrolysis and biotransformation of lignocellulose, i.e., biorefinery, can provide human beings with biofuels, bio-based chemicals, and materials, and is an important technology to solve the fossil energy crisis and promote global sustainable development. Biorefinery involves steps such as pretreatment, saccharification, and fermentation, and researchers have developed a variety of biorefinery strategies to optimize the process and reduce process costs in recent years. Lignocellulosic hydrolysates are platforms that connect the saccharification process and downstream fermentation. The hydrolysate composition is closely related to biomass raw materials, the pretreatment process, and the choice of biorefining strategies, and provides not only nutrients but also possible inhibitors for downstream fermentation. In this review, we summarized the effects of each stage of lignocellulosic biorefinery on nutrients and possible inhibitors, analyzed the huge differences in nutrient retention and inhibitor generation among various biorefinery strategies, and emphasized that all steps in lignocellulose biorefinery need to be considered comprehensively to achieve maximum nutrient retention and optimal control of inhibitors at low cost, to provide a reference for the development of biomass energy and chemicals.
Assuntos
Biomassa , Lignina , Lignina/química , Hidrólise , Fermentação , Biocombustíveis , Nutrientes/metabolismoRESUMO
Inflammation and oxidative stress caused by fine particulate matter (PM2.5) increase the incidence and mortality rates of respiratory disorders. Rosavin is the main chemical component of Rhodiola plants, which exerts anti-oxidative and antiinflammatory effects. In this research, the potential therapeutic effect of rosavin was investigated by the PM2.5-induced lung injury rat model. Rats were instilled with PM2.5 (7.5 mg/kg) suspension intratracheally, while rosavin (50 mg/kg, 100 mg/kg) was delivered by intraperitoneal injection before the PM2.5 injection. It was observed that rosavin could prevent lung injury caused by PM2.5. PM2.5 showed obvious ferroptosis-related ultrastructural alterations, which were significantly corrected by rosavin. The pretreatment with rosavin downregulated the levels of tissue iron, malondialdehyde, and 4-hydroxynonenal, and increased the levels of glutathione. The expression of nuclear factor E2-related factor 2 (Nrf2) was upregulated by rosavin, together with other ferroptosis-related proteins. RSL3, a specific ferroptosis agonist, reversed the beneficial impact of rosavin. The network pharmacology approach predicted the activation of rosavin on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. LY294002, a potent PI3K inhibitor, decreased the upregulation of Nrf2 induced by rosavin. In conclusion, rosavin prevented lung injury induced by PM2.5 stimulation and suppressed ferroptosis via upregulating PI3K/Akt/Nrf2 signaling pathway.
Assuntos
Lesão Pulmonar , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Lesão Pulmonar/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Estresse Oxidativo , Material Particulado/toxicidadeRESUMO
High-altitude cardiac injury (HACI) is one of the common tissue injuries caused by high-altitude hypoxia that may be life threatening. Notoginsenoside R1 (NG-R1), a major saponin of Panax notoginseng, exerts anti-oxidative, anti-inflammatory, and anti-apoptosis effects, protecting the myocardium from hypoxic injury. This study aimed to investigate the protective effect and molecular mechanism of NG-R1 against HACI. We simulated a 6000 m environment for 48 h in a hypobaric chamber to create a HACI rat model. Rats were pretreated with NG-R1 (50, 100 mg/kg) or dexamethasone (4 mg/kg) for 3 days and then placed in the chamber for 48 h. The effect of NG-R1 was evaluated by changes in Electrocardiogram parameters, histopathology, cardiac biomarkers, oxidative stress and inflammatory indicators, key protein expression, and immunofluorescence. U0126 was used to verify whether the anti-apoptotic effect of NG-R1 was related to the activation of ERK pathway. Pretreatment with NG-R1 can improve abnormal cardiac electrical conduction and alleviate high-altitude-induced tachycardia. Similar to dexamethasone, NG-R1 can improve pathological damage, reduce the levels of cardiac injury biomarkers, oxidative stress, and inflammatory indicators, and down-regulate the expression of hypoxia-related proteins HIF-1α and VEGF. In addition, NG-R1 reduced cardiomyocyte apoptosis by down-regulating the expression of apoptotic proteins Bax, cleaved caspase 3, cleaved caspase 9, and cleaved PARP1 and up-regulating the expression of anti-apoptotic protein Bcl-2 through activating the ERK1/2-P90RSK-Bad pathway. In conclusion, NG-R1 prevented HACI and suppressed apoptosis via activation of the ERK1/2-P90RSK-Bad pathway, indicating that NG-R1 has therapeutic potential to treat HACI.
RESUMO
Disseminated intravascular coagulation (DIC), which is closely related to platelet activation, is a key factor leading to high mortality in sepsis. The release of contents from plasma membrane rupture after platelet death further aggravates thrombosis. Nerve injury-induced protein 1 (NINJ1) is a cell membrane protein that mediates membrane disruption, a typical marker of cell death, through oligomerization. Nevertheless, whether NINJ1 is expressed in platelets and regulates the platelet function remains unclear. The aim of this study was to evaluate the expression of NINJ1 in human and murine platelets and elucidate the role of NINJ1 in platelets and septic DIC. In this study, NINJ1 blocking peptide (NINJ126-37) was used to verify the effect of NINJ1 on platelets in vitro and in vivo. Platelet αIIbß3 and P-selectin were detected by flow cytometry. Platelet aggregation was measured by turbidimetry. Platelet adhesion, spreading and NINJ1 oligomerization were examined by immunofluorescence. Cecal perforation-induced sepsis and FeCl3-induced thrombosis models were used to evaluate the role of NINJ1 in platelet, thrombus and DIC in vivo. We found that inhibition of NINJ1 alleviates platelet activation in vitro. The oligomerization of NINJ1 is verified in membrane-broken platelets, which is regulated by the PANoptosis pathway. In vivo studies demonstrate that inhibition of NINJ1 effectively reduces platelet activation and membrane disruption, thus suppressing platelet-cascade reaction and leading to anti-thrombosis and anti-DIC in sepsis. These data demonstrate that NINJ1 is critical in platelet activation and plasma membrane disruption, and inhibition of NINJ1 effectively reduces platelet-dependent thrombosis and DIC in sepsis. This is the first study to reveal the key role of NINJ1 in platelet and its related disorders.
Assuntos
Moléculas de Adesão Celular Neuronais , Coagulação Intravascular Disseminada , Fatores de Crescimento Neural , Sepse , Trombose , Animais , Humanos , Camundongos , Plaquetas/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Fatores de Crescimento Neural/metabolismo , Ativação Plaquetária , Agregação Plaquetária , Sepse/metabolismo , Trombose/metabolismoRESUMO
Recent studies showed that in responding of pathogens stimulation, immune cells and other cells display memory-like effects. Platelets are primary effectors of hemostasis and thrombosis which also participate in immune responses. However, there is no relevant research on whether memory-like effect exists in platelets. In our study after recovery from repetitive LPS stimulus, platelets aggregation, diffusion and clot retraction exhibit a significant reduction. It proves that memory-like response could be aroused in platelets. Furthermore, in the mouse arterial thrombosis model, LPS pretreated platelets showed lower integrin activation, shorter thrombus length and longer occlusion time, indicating that the memory-like response of platelet could alleviate arterial thrombosis. Moreover, memory-like response of platelets was also found to be related to PI3K/AKT signaling pathway. The decreased mitochondrial DNA methylation reveal that platelet memory-like responses may be produced from epigenetic reprogramming. Our research proves for the first time that memory-like response in platelets protects mice from arterial thrombosis, extends the understanding of trained memory.
Assuntos
Plaquetas , Trombose , Animais , Plaquetas/metabolismo , Modelos Animais de Doenças , Hemostasia , Lipopolissacarídeos/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Ativação Plaquetária , Agregação Plaquetária , Trombose/metabolismoRESUMO
Fine particulate matter (PM2.5) exposure can cause lung injury and a large number of respiratory diseases. Sipeimine is a steroidal alkaloid isolated from Fritillaria roylei which has been associated with anti-inflammatory, antitussive and antiasthmatic properties. In this study, we explored the potential effects of sipeimine against PM2.5-induced lung injury in Sprague Dawley rats. Sipeimine alleviated lung injury caused by PM2.5 and decreased pulmonary edema, inflammation and the levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the bronchoalveolar lavage fluid. In addition, sipeimine upregulated the glutathione (GSH) expression and downregulated the expression of 4-hydroxynonenal (4-HNE), tissue iron and malondialdehyde (MDA). The downregulation of proteins involved in ferroptosis, including nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1) and solute carrier family 7 member 11 (SLC7A11) was reversed by sipeimine. The administration of RSL3, a potent ferroptosis-triggering agent, blocked the effects of sipeimine. Using network pharmacology, we found that the effects of sipeimine were presumably mediated through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. A PI3K inhibitor (LY294002) blocked the PI3K/Akt signaling pathway and reversed the effects of sipeimine. Overall, this study suggested that the protective effect of sipeimine against PM2.5-induced lung injury was mainly mediated through the PI3K/Akt pathway, ultimately leading to a reduction in ferroptosis.
Assuntos
Cevanas , Ferroptose , Lesão Pulmonar , Material Particulado , Animais , Cevanas/farmacologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Farmacologia em Rede , Material Particulado/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The imbalance of intestinal microbiota and inflammatory response is crucial in the development of lung injury induced by PM2.5. In recent years, probiotics have attracted great attention for their health benefits in inflammatory diseases and regulating intestinal balance, but their intricate mechanisms need further experiments to elucidate. In our research, a rat lung damage model induced by PM2.5 exposure in real environment was established to explore the protective properties of probiotics on PM2.5 exposure injury and its related mechanism. The results indicated that compared with the AF control group, rats in the PM2.5 group gained weight slowly, ate less and had yellow hair. The results of pathological and immunohistochemical examinations showed that the inflammatory infiltration of lung tissue was alleviated after probiotic treatment. The Lung function results also showed the improvement effects of probiotics administration. In addition, probiotics could promote the balance of Th17 and Treg cells, inhibit cytokines expression (TNF-α, IL-6, IL-1ß, IL-17A), and increase the concentration of anti-inflammatory factors (IL-10, TGF-ß). In addition, 16 S rRNA sequence analysis showed that probiotic treatment could reduce microbiota abundance and diversity, increase the abundance of possible beneficial bacteria, and decrease the abundance of bacteria associated with inflammation. In general, probiotic intervention was found to have preventive effects on the occurrence of PM2.5 induced pathological injury, and the mechanism was associate with to the inhibition of inflammatory response, regulation of Th17/Treg balance and maintenance of intestinal internal environment stability.
Assuntos
Microbioma Gastrointestinal , Lesão Pulmonar , Pneumonia , Probióticos , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Lesão Pulmonar/prevenção & controle , Material Particulado/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Pneumonia/prevenção & controle , Probióticos/farmacologia , Ratos , Linfócitos T Reguladores/metabolismo , Células Th17 , Fator de Crescimento Transformador beta , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The outcomes of patients with refractory benign esophageal strictures (RBES) are unclear, and the clinical efficacy of dilation versus stent placement is lacking. Our objective was to explore the role of endoscopic dilation and stents placement in the management of RBES. METHODS: RBES patients treated with dilation and stents in our hospital between January 2009 and December 2017 were included in this study. The primary outcomes were to assess clinical effectiveness and adverse events. The secondary outcome was to identify factors that predicted the dysphagia-free period. RESULTS: Among 75 RBES patients (54 male; median age 59 years), 39 (52%), 20 (26.7%), 3 (4%), 10 (13.3%), and 3 (4%), were postsurgical, post-ESD, achalasia of cardia, caustic and mixed etiology, respectively. The median number of endoscopic therapy was 5 times (range 3, 21). Endoscopic therapy was successful in 46 patients (61.3%). Patients treated with dilation showed a higher success rate (70.9%, 39/55) than that treated with stents (35%, 7/20). Fifteen patients died during follow-up. Nineteen patients had adverse events after endoscopic therapy. In total, the mean dysphagia-free period was 3.4 months (95% CI, 2.5-4.3). The patients treated with dilation demonstrated a dysphagia-free period of 3.7 months (95% CI, 2.7-5), while patients treated with stents displayed a dysphagia-free period of 2.3 months (95% CI, 1.5-3). The dysphagia-free period had a linear growth trend over time, with an increase of 12 days per endoscopic therapy. CONCLUSION: The dysphagia-free period increased by 12 days per endoscopic therapy, so the endoscopic therapy tended to be effective in patients with RBES by increasing the dysphagia-free period. However, compared to dilation therapy, stent therapy was not effective in increasing the dysphasia-free period and reducing the times and frequency of dilation. In addition, univariate and multivariate analyses also indicated that etiology may predict the endoscopic therapy outcome. TRIAL REGISTRATION: This study was retrospectively registered and approved by the Ethics Committee of West China Hospital of Sichuan University (IRB number: ChiCTR1800016321 ).
Assuntos
Transtornos de Deglutição/cirurgia , Dilatação/métodos , Estenose Esofágica/cirurgia , Esofagoscopia/métodos , Stents , Transtornos de Deglutição/etiologia , Estenose Esofágica/etiologia , Esofagoscopia/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the accuracy of endoscopic ultrasound (EUS) and magnifying endoscopy with narrow-band imaging (ME-NBI) in evaluating the invasion depth of early esophageal carcinoma. METHODS: Patients who underwent endoscopic resection for early esophageal cancer from March 2013 to October 2017 were enrolled. The EUS and ME-NBI results were compared with the pathology results. RESULTS: A total of 392 lesions from 333 patients were assessed, including 83 mild and moderate dysplasia, 72 severe dysplasia, 235 squamous cell carcinoma, and 2 adenosquamous carcinoma. About 308 lesions were given EUS only, 7 had ME-NBI only, 77 underwent both EUS and ME-NBI. EUS resulted in a 43.9% accuracy for the 385 lesions, with poor consistency (Kappa=0.1) with the pathology results. But higher accuracy (68.2%) was found for lesions infiltrating into the submucosa of the lesions, compared with 40.5% for lesions contained within the mucosa (P=0.001). ME-NBI resulted in a 72.6% accuracy for the 84 lesions, with a medium consistency (Kappa=0.4). The accuracy for lesions contained within the mucosa was 91.0%, compared with 16.7% for lesions infilrtrating into the submucosa (P=0.001). EUS and ME-NBI for the 77 lesions demonstrated an accuracy of 42.9% for the EUS and 84.3% for the ME-NBI (P=0.001). CONCLUSIONS: ME-NBI has higher accuracy than EUS in evaluating the invasion depth of early esophageal carcinoma.
Assuntos
Colesterol/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Regulação para CimaRESUMO
Objective: Rheumatoid arthritis (RA) is an autoimmune disease. The role of Th17/Treg balance in RA pathogenesis has been increasingly emphasized. In this study, bibliometric and visualization analyses of the top 100 most cited articles on Th17/Treg balance in the field of RA were conducted. Methods: By searching the Web of Science Core Collection database, the top 100 most cited articles of related studies were included, and the authors, countries, institutions, journals, keywords and other information were extracted for analysis using VOSviewer software. Results: The top 100 most cited papers had a total of 7185 citations, with an average citation frequency of 72 (range 21-730). All of them were published between 2011 and 2022. The most influential paper, with 730 citations, was written by "Komatsu, Noriko" in 2014 and published in NATURE MEDICINE. The author with the highest output was "Cho, Mi-La" (n = 24). China was the country with the highest number of publications (n = 42). Catholic University of Korea was the institution with the highest number of publications (n = 24). ARTHRITIS AND RHEUMATISM (n = 7), ARTHRITIS & RHEUMATOLOGY (n = 7) and INTERNATIONAL IMMUNOPHARMACOLOGY (n = 7) were the journals that published the most literature. "Expression" (cytokines and transcription factors, etc) and "differentiation" (T cells, Treg cells, and Th17 cells) were the themes of the research. "Mechanisms", "gut microbiota", "STAT3", "interleukin-6", "synovial fibroblasts" were the hot spots of research in recent years. Conclusions: For the first time, the top 100 most cited articles were analyzed using bibliometric methods. We aimed to grasp the current development and research trends of RA and Th17/Treg-related studies. It is hoped that this study will provide direction and support for future research.
RESUMO
Background: Jinshuibao capsules has been utilized in treating stable chronic obstructive pulmonary disease (COPD) for a long time. While the evidence-based evidence and network pharmacology to clarify the therapeutic efficacy and pharmacological mechanisms of Jinshuibao capsules have remained elusive. Objectives: Integrating evidence-based medicine and network pharmacology to explain the therapeutic efficacy and pharmacological mechanisms of Jinshuibao capsules for stable COPD. Methods: Cochrane Library, Web of Science, EMBASE, PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Information Resource Integration Service Platform (CQVIP), and China Biomedicine (SinoMed) databases were searched. Studies were selected according to the inclusion and exclusion criteria. Statistical analysis was performed using the RevMan 5.3 software (Cochrane, London, UK). In network pharmacology, components of Jinshuibao capsules were screened, stable COPD-related genes were then identified and the 'component-target-pathway' network constructed. Results: Meta-analysis revealed that Jinshuibao capsules exerts therapeutic effects on stable COPD by increasing the levels of FEV1% pred, FEV1/FVC ratio, FEV1, FVC, and PaO2 while decreasing the level of PaCO2. In addition, Jinshuibao capsules could effectively increase the levels of CD3+, CD4+/CD8+ ratio, Th17/Treg ratio, and SOD while reduce the levels of IL-8 and TNF-α. Network pharmacology identified 22 active compounds and 419 intersection gene targets. AKT1, SRC, MAPK1, STAT3, and MAPK3 were top 5 key target proteins. Besides, 20 potential pathways of Jinshuibao capsules on stable COPD were identified, like endocrine resistance, AGE-RAGE signaling pathway in diabetic complications, and chemical carcinogenesis-receptor activation. Conclusion: Jinshuibao capsules could positively influence patients with stable COPD, while the efficacy and safety of Jinshuibao capsules in the treatment of COPD could not be reliably confirmed. These findings suggest that Jinshuibao capsules exerts effect on stable COPD through multi-target, multi-component and multi-pathway mechanism. Future studies may explore the active components of Jinshuibao capsules.
RESUMO
BACKGROUND: The pinewood nematode (Bursaphelenchus xylophilus) causes severe damage to pine trees. The nematophagous fungus, Esteya vermicola, exhibits considerable promise in the biological control of Bursaphelenchus xylophilus due to its infectivity. Notably, the lunate conidia produced by E. vermicola can infect Bursaphelenchus xylophilus. In the study, we aim to investigate the genes involved in the formation of the lunate conidia of E. vermicola CBS115803. RESULTS: Esteya vermicola CBS115803 yielded 95% lunate conidia on the complete medium (CM) and 86% bacilloid conidia on the minimal medium (MM). Transcriptomic analysis of conidia from both media revealed a significant enrichment of differentially expressed genes in the pathway related to 'cellular amino acid biosynthesis and metabolism'. Functional assessment showed that the knockout of two arginine biosynthesis genes (EV232 and EV289) resulted in defects in conidia germination, mycelial growth, lunate conidia formation, and virulence of E. vermicola CBS115803 in Bursaphelenchus xylophilus. Remarkably, the addition of arginine to the MM improved mycelial growth, conidiation and lunate conidia formation in the mutants and notably increased conidia yield and the lunate conidia ratio in the wild-type E. vermicola CBS115803. CONCLUSION: This investigation confirms the essential role of two arginine biosynthesis genes in lunate conidia formation in E. vermicola CBS115803. The findings also suggest that the supplementation of arginine to the culture medium can enhance the lunate conidia yield. These insights contribute significantly to the application of E. vermicola CBS115803 in managing Bursaphelenchus xylophilus infections. © 2023 Society of Chemical Industry.