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In this study, we prepared bionic selenium-baicalein nanoparticles (ACM-SSe-BE) for the targeted treatment of nonsmall cell lung cancer. Due to the coating of the A549 membrane, the system has homologous targeting capabilities, allowing for the preparation of target tumor cells. The borate ester bond between selenium nanoparticles (SSe) and baicalein (BE) is pH-sensitive and can break under acidic conditions in the tumor microenvironment to achieve the targeted release of BE at the tumor site. Moreover, SSe further enhances the antitumor effect of BE by increasing the production of ROS in tumor cells. Transmission electron microscopy (TEM) images and dynamic light scattering (DLS) showed that the ACM-SSe-BE had a particle size of approximately 155 ± 2 nm. FTIR verified the successful coupling of SSe and BE. In vitro release experiments indicated that the cumulative release of ACM-SSe-BE at pH 5.5 after 24 h was 69.39 ± 1.07%, which was less than the 20% release at pH 7.4, confirming the pH-sensitive release of BE in ACM-SSe-BE. Cell uptake experiments and in vivo imaging showed that ACM-SSe-BE had good targeting ability. The results of MTT, flow cytometry, Western blot, and cell immunofluorescence staining demonstrated that ACM-SSe-BE promoted A549 cell apoptosis and inhibited cell proliferation. The in vivo antitumor results were consistent with those of the cell experiments. These results clearly suggested that ACM-SSe-BE will be a promising bionic nanosystem for the treatment of nonsmall cell lung cancer.
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Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.
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BACKGROUND: Pleural effusion caused by fibrosing mediastinitis is rarely reported. This study aimed to summarize the clinical manifestations, diagnosis and treatment of transudative pleural effusion due to fibrosing mediastinitis. METHODS: Medical records and follow-up data of 7 patients with transudative pleural effusion due to fibrosing mediastinitis in Beijing Chaoyang Hospital between May 2014 and Feb 2018 were retrospectively analyzed. RESULTS: These patients included 4 males and 3 females, with an average age of (64 ± 9) years. There were 3 left-sided effusions, 2 right-sided effusions and 2 bilateral effusions. Previous or latent tuberculosis was found in 6 patients. Pulmonary hypertension was indicated by echocardiography in all the 7 patients. Computed tomography pulmonary angiography (CTPA) of all the 7 cases showed increased soft tissue images visible in the mediastinum and bilateral hilus, different degrees of stenosis or occlusion in the pulmonary artery and pulmonary vein. In addition, 4 cases were found of right middle lobe atelectasis with a mediastinal window setting. There was interstitial pulmonary edema on the side of pleural effusion with a lung window setting. All the 7 patients were treated with intermittent drainage of pleural effusion combined with diuretic therapy. Five patients were treated with antituberculosis therapy. Up to now, two patients died of right heart failure and respiratory failure after 2 and 16 months respectively; The remaining 5 patients were still in follow up. CONCLUSION: Fibrosing mediastinitis can lead to pulmonary vein stenosis or occlusion, and thus cause transudative pleural effusion, which can be detected by CTPA. Pulmonary hypertension, long time of cough, and a history of tuberculosis are common in these patients. The common therapy is intermittent drainage of pleural effusion combined with diuretic therapy.
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Mediastinite , Derrame Pleural , Esclerose , Humanos , Masculino , Feminino , Mediastinite/complicações , Mediastinite/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Derrame Pleural/etiologia , Derrame Pleural/diagnóstico por imagem , Esclerose/complicaçõesRESUMO
Background/purpose: The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. Results: There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012-2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. Conclusion: This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research.
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In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.
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Apoptose , Neoplasias da Mama , Lipossomos , Receptor ErbB-2 , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Feminino , Lipossomos/química , Trastuzumab/administração & dosagem , Trastuzumab/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Terapia de Alvo Molecular , Acrilamidas , AminoquinolinasRESUMO
Grain chalkiness is an undesirable trait that negatively regulates grain yield and quality in rice. However, the regulatory mechanism underlying chalkiness is complex and remains unclear. We identified a positive regulator of white-belly rate (WBR). The WBR7 gene encodes sucrose synthase 3 (SUS3). A weak functional allele of WBR7 is beneficial in increasing grain yield and quality. During the domestication of indica rice, a functional G/A variation in the coding region of WBR7 resulted in an E541K amino acid substitution in the GT-4 glycosyltransferase domain, leading to a significant decrease in decomposition activity of WBR7A (allele in cultivar Jin23B) compared with WBR7G (allele in cultivar Beilu130). The NIL(J23B) and knockout line NIL(BL130)KO exhibited lower WBR7 decomposition activity than that of NIL(BL130) and NIL(J23B)COM, resulting in less sucrose decomposition and metabolism in the conducting organs. This caused more sucrose transportation to the endosperm, enhancing the synthesis of storage components in the endosperm and leading to decreased WBR. More sucrose was also transported to the anthers, providing sufficient substrate and energy supply for pollen maturation and germination, ultimately leading to an increase rate of seed setting and increased grain yield. Our findings elucidate a mechanism for enhancing rice yield and quality by modulating sucrose metabolism and allocation, and provides a valuable allele for improved rice quality.
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The issue of urban resilience plays great significance and value for the sustainable development of cities, which has attracted increasing attention from scholars and governments, especially in the western region of China. Based on the Production-Living-Ecological (PLE) system, this study attempts to describe urban resilience by the combination system that contains with P,L,E subsystem. The integrated approach including FAHP-EM,GRA-TOPSIS, CCDM, and ODM is proposed to reveal the urban resilience level and seek out the key constraints' indicators. Then, an empirical analysis of panel data of 18 cities in Sichuan Province from 2011 to 2021 was conducted to analyze the development process. The valuation results suggested that:(1)for urban resilience level, most cities at the moderate imbalance level and basically maintained at this level, only Chengdu is reaching the basic coordination level since in 2013.(2)The insufficient development of P,L,E subsystem is the reason for the moderate imbalance development, especially the key limiting factor is the P subsystem's low development level.(3)the most prominent obstacle indicators are x1(per capita local financial expenditure on science and technology), x2(per capita of R&D spending), x8(total export-import per capita), x14(number of people with basic medical insurance), x22(length of urban drainage pipeline), x23(number of public toilets per person) and the contribution values reach 7.56%,7.49%,11.02%, 9.14%,12.53%, 12.60% respectively. The detailed reference suggestions and effective measures put forwarded for policy makers and planners to promote urban resilience in Western China.
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Cidades , China , Humanos , Desenvolvimento Sustentável , Conservação dos Recursos Naturais , EcossistemaRESUMO
Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/tratamento farmacológico , Medicina Tradicional Chinesa , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipófise-Suprarrenal/patologia , Sistema Nervoso Central , Isquemia Encefálica/terapia , Sistema Imunitário , InflamaçãoRESUMO
Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.
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Artrite Reumatoide , Isoquinolinas , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Antirreumáticos/farmacologia , Antirreumáticos/química , Antirreumáticos/síntese química , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Relação Dose-Resposta a Droga , Descoberta de Drogas , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoquinolinas/química , Isoquinolinas/farmacologia , Isoquinolinas/síntese química , Estrutura Molecular , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Quinolonas/síntese química , Quinolonas/química , Quinolonas/farmacologiaRESUMO
The quality of rice, evaluated using multiple quality-related traits, is the main determinant of its market competitiveness. In this study, two japonica rice varieties with significant differences in quality-related traits were used as parents to construct two populations, BC3F2 and BC3F2:3, with Kongyu131 (KY131) as the recurrent parent. A genetic linkage map was constructed using the BC3F2 population based on 151 pairs of SSR/InDel polymorphic markers selected between the parents. Grain-shape-related traits (grain length GL, grain width GW, and length-to-width ratio LWR), chalkiness-related traits (white-core rate WCR, white-belly rate WBR, white-back rate BR, and chalkiness rate CR), and amylose content (AC) were investigated in the two populations in 2017 and 2018. Except for BR and CR, the traits showed similar characteristics with a normal distribution in both populations. Genetic linkage analysis was conducted for these quality-related traits, and a total of 37 QTLs were detected in the two populations. Further validation was performed on the newly identified QTLs with larger effects, and three grain shape QTLs and four chalkiness QTLs were successfully validated in different environments. One repeatedly validated QTL, qWCR3, was selected for fine mapping and was successfully narrowed down to a 100 kb region in which only two genes, LOC_0s03g45210 and LOC_0s03g45320, exhibited sequence variations between the parents. Furthermore, the variation of LOC_Os03g45210 leads to a frameshift mutation and premature protein termination. The results of this study provide a theoretical basis for positional cloning of the qWCR3 gene, thus offering new genetic resources for rice quality improvement.
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Mapeamento Cromossômico , Ligação Genética , Oryza , Fenótipo , Locos de Características Quantitativas , Oryza/genética , Mapeamento Cromossômico/métodos , Grão Comestível/genética , Cromossomos de Plantas/genética , Genes de PlantasRESUMO
Objectives: In recent years, there has been an increase in the number of randomized clinical trials of BTX-A combined with ESWT for the treatment of post-stroke spasticity. This has made it possible to observe the benefits of combination therapy in clinical practice. Therefore, this paper reviews the effectiveness of BTX-A in combination with ESWT for the treatment of post-stroke spasticity. Methods: By October 2023, a systematic review was conducted in the databases PubMed, Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, China Biology Medicine disc and China Science and Technology Journal Database were systematically searched. We included randomized controlled trials that reported outcome metrics such as MAS, FMA, and MBI score. Studies were excluded if MAS was not reported. The quality of the included studies was assessed by the Cochrane Collaboration's tool for assessing risk of bias, and the AMSTAR quality rating scale was selected for self-assessment. Results: A total of 70 articles were included in the initial search, and six were ultimately included. The results of the included studies showed that the combination therapy was effective in reducing MAS scores and improving FMA and MBI scores in patients with spasticity compared to the control group. Combination therapy has also been shown to improve joint mobility and reduce pain in spastic limbs. Conclusion: Cumulative evidence from clinical randomized controlled trial studies suggests that the combination therapy is effective in reducing lower limb spasticity and improving mobility after stroke. However, more clinical trials are still needed to corroborate the evidence regarding the efficacy of BTX-A combined with shockwave therapy. Systematic Review Registration: The system review can be searched in the PROSPERO database (CRD42023476654).
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BACKGROUND: Preschooling is a critical time for intervention in children with autism spectrum disorder (ASD); thus, we analyzed brain tissue component volumes (BTCVs) and clinical indicators in preschool children with ASD to identify new biomarkers for early screening. METHODS: Eighty preschool children (3-6 years) with ASD were retrospectively included. The whole-brain myelin content (MyC), white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and non-WM/GM/MyC/CSF brain component volumes were obtained using synthetic magnetic resonance imaging (SyMRI). Clinical data, such as intelligence scores, autism diagnostic observation schedule-calibrated severity scores, age at first production of single words (AFSW), age at first production of phrases (AFP), and age at walking onset (AWO), were also collected. The correlation between the BTCV and clinical data was evaluated, and the effect of BTCVs on clinical data was assessed by a regression model. RESULTS: WM and GM volumes were positively correlated with intelligence scores (both P < 0.001), but WM and GM did not affect intelligence scores (P = 0.116, P = 0.290). AWO was positively correlated with AFSW and AFP (both P < 0.001). The multivariate linear regression analysis revealed that MyC, AFSW, AFP, and AWO were significantly different (P = 0.005, P < 0.001, P < 0.001). CONCLUSIONS: This study revealed positive correlations between WM and GM volumes and intelligence scores. Whole-brain MyC affected AFSW, AFP, and AWO in preschool children with ASD. Noninvasive quantification of BTCVs via SyMRI revealed a new visualizable and quantifiable biomarker (abnormal MyC) for early ASD screening in preschool children.
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OBJECTIVE: This study aimed to investigate the roles of nuclear factor-kappa B p65 (NF-[Formula: see text]B p65) and tumor necrosis factor-α (TNF-α) in cell apoptosis occurring in the fetal membranes of pregnant women who experience preterm premature rupture of membranes (PPROM). METHODS: This was a case-control study involving 57 pregnant women who delivered in the obstetric department of Affiliated Loudi Hospital, Hengyang Medical School, University of South China, from June 2021 to June 2022. Samples of fetal membrane tissue were collected from pregnant women with PPROM (n=27) and pregnant women who had normal deliveries (control group; n=30). The membrane tissue morphology of both groups was observed, and the expression of NF-[Formula: see text]B p65, p-NF-[Formula: see text]B p65, TNF-α, and caspase-3 was detected. Apoptosis in fetal membranes was examined. RESULTS: Morphological evaluation of the fetal membrane tissues obtained from patients with PPROM revealed an abnormal structure with a thin collagen fiber layer and cells with a largely vacuolar cytoplasm. There was a positive correlation between the expression of p-NF-[Formula: see text]B p65/NF-[Formula: see text]B p65 and cell apoptosis (r1 =0.89, R2 =0.805, P=0.00). Furthermore, TNF-α was positively correlated with fetal membrane cell apoptosis (r2 =0.93, R2=0.881, P=0.00). CONCLUSION: NF-[Formula: see text]B p65 is involved in the occurrence of PPROM by promoting the expression of TNF-α, which upregulates caspase-3 to cause apoptosis of fetal membrane cells.
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Apoptose , Membranas Extraembrionárias , Ruptura Prematura de Membranas Fetais , Fator de Transcrição RelA , Fator de Necrose Tumoral alfa , Feminino , Humanos , Gravidez , Estudos de Casos e Controles , Caspase 3/metabolismo , Membranas Extraembrionárias/metabolismo , Membranas Extraembrionárias/patologia , Ruptura Prematura de Membranas Fetais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Transcrição RelA/metabolismo , AdultoRESUMO
Cutaneous squamous cell carcinoma (cSCC) is an invasive malignancy that disproportionately afflicts immunosuppressed individuals. The close associations of cSCC with immunosuppression and human papillomavirus (HPV) infection beget the question of how these three entities are intertwined in carcinogenesis. By exploring the role of T cell immunity in HPV-related cSCC based on the existing literature, we found that the loss of T cell immunity in the background of ß-HPV infection promotes cSCC initiation following exposure to environmental carcinogens or chronic trauma. This highlights the potential of developing T-cell centred therapeutic and preventive strategies for populations with increased cSCC risk.
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Nanoparticles as cancer therapeutic carrier fail in clinical translation due to complex biological environments in vivo consisting of electrolytes and proteins which render nanoparticle aggregation and unable to reach action site. This review identifies the desirable characteristics of nanoparticles and their constituent materials that prevent aggregation from site of administration (oral, lung, injection) to target site. Oral nanoparticles should ideally be 75-100 nm whereas the size of pulmonary nanoparticles minimally affects their aggregation. Nanoparticles generally should carry excess negative surface charges particularly in fasting state and exert steric hindrance through surface decoration with citrate, anionic surfactants and large polymeric chains (polyethylene glycol and polyvinylpyrrolidone) to prevent aggregation. Anionic as well as cationic nanoparticles are both predisposed to protein corona formation as a function of biological protein isoelectric points. Their nanoparticulate surface composition as such should confer hydrophilicity or steric hindrance to evade protein corona formation or its formation should translate into steric hindrance or surface negative charges to prevent further aggregation. Unexpectedly, smaller and cationic nanoparticles are less prone to aggregation at cancer cell interface favoring endocytosis whereas aggregation is essential to enable nanoparticles retention and subsequent cancer cell uptake in tumor microenvironment. Present studies are largely conducted in vitro with simplified simulated biological media. Future aggregation assessment of nanoparticles in biological fluids that mimic that of patients is imperative to address conflicting materials and designs required as a function of body sites in order to realize the future clinical benefits.
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Nanopartículas , Neoplasias , Coroa de Proteína , Humanos , Coroa de Proteína/metabolismo , Nanopartículas/metabolismo , Polímeros , Polietilenoglicóis , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Microambiente TumoralRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The Kadsura coccinea (Lem.) A. C. Smith is known as "Heilaohu" of the Tujia ethnomedicine in China. It has anti-tumor, anti-oxidation, anti-HIV, anti-inflammatory and liver protective effects, used to treat diseases such as rheumatoid arthritis, cancer, gastritis and hepatitis. In this research, we investigated the anti-fibrotic effect and possible mechanisms of acetylbinankadsurin A (ACBA) in vitro and in vivo, which is a natural compound derived from roots of K. coccinea. AIM OF THE STUDY: We try to evaluate the efficacy of ACBA in the treatment of liver fibrosis and to explore the underlying mechanisms of ACBA by network pharmacology, machine learning, molecular docking, molecular dynamics simulations, and experimental assessment. MATERIALS AND METHODS: ACBA was isolated from the CH2Cl2 layer of the roots of K. coccinea through column chromatographic techniques. The structure of ACBA was determined by using 1D and 2D NMR. CCl4-induced C57BL/6 mouse liver fibrosis models were established to evaluate the anti-fibrosis effects of ACBA in vivo. The molecular targets of ACBA and liver fibrosis were obtained from various databases, then constructed a protein-protein interaction (PPI) networks through the STRING database. Gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were applied using the "clusterProfiler" R package. Furthermore, the key genes for ACBA treatment of liver fibrosis were identified by the least absolute shrinkage and selection operator (LASSO). Molecular docking and molecular dynamics simulations were also carried out. Finally, the target and pathway of ACBA were verified by immunofluorescence staining, RT-PCR and Western blot. RESULT: First, ACBA attenuated CCl4-induced liver injury and fibrosis in vivo. These findings were accompanied by decreased expression of α-SMA and collagen I. Second, ACBA significantly decreased serum levels of ALT, AST, TNF-α and IL-6. Then, we identified 133 potential targets of ACBA and 7987 targets of liver fibrosis. KEGG analysis showed that ACBA could regulate the drug metabolism - cytochrome P450, fructose and mannose metabolism, IL-17 and NF-κB signaling pathways. Next, six core targets was screened by LASSO analysis including AKR1B1, PFKFB3, EPHA3, CDK1, CCR1 and CYP3A4. Molecular docking showed that ACBA has a good binding affinity for CCR1. Furthermore, compared with CCR1 inhibitor BX-471, The results of molecular simulation dynamics showed that ACBA was stable in binding with CCR1. Consistently, ACBA remarkably downregulated the expression of CCR1, p-NF-κBp65, p-IκBα, p-STAT1 and TNF-α proteins, which were upregulated in CCl4-induced hepatic fibrosis and LPS-THP-1 cells. CONCLUSION: Our results suggest that ACBA significantly attenuated CCl4-induced liver fibrosis in histopathological and in serum level. This effect may be mediated by CCR1, NF-κB and STAT1 signalling.
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Medicamentos de Ervas Chinesas , Simulação de Dinâmica Molecular , Camundongos , Animais , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Farmacologia em Rede , NF-kappa B , Cirrose Hepática/tratamento farmacológico , Aprendizado de Máquina , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
Background: Magnetic resonance sialography (MRS) can be used to clearly examine the main duct of the parotid and is widely applied in the diagnosis of chronic obstructive parotitis (COP). However, there are few studies on the classification, treatment options and prognosis of COP using MRS. Methods: Clinical and imaging data were retrospectively collected from 41 patients with COP between January 2010 and December 2020 at the Ninth People's Hospital affiliated with Shanghai Jiao Tong University School of Medicine. All patients underwent MRS and were treated with intraductal irrigation. The patients were divided into 2 groups according to the presence or absence of symptomatic relapse during the 6-month follow-up period. The imaging features of parotid MRS included three parts: gland volume, stenosis classification and dilatation classification. The location/length of dilatation, the widest diameter of the dilated duct, and the condition of the branch ducts were also recorded and compared between the groups. Results: A mean of 14.8±12.3 irrigations were performed. There were 15 patients with recurrence and 26 without recurrence. There was no significant difference in the parotid volume (P=0.460), stenosis grade (P=0.738) or maximum diameter of dilatation of the branch duct (P=0.723) between the recurrence and non-recurrence groups. Statistically significant differences were found in dilatation classification (P=0.009), length of dilatation (P=0.043), condition of the branch ducts (P=0.017) and dexamethasone use (P=0.031). Conclusions: MRS is an available diagnostic and grading modality for COP. The imaging features and classification of the parotid main duct in MRS could be helpful for treatment selection. Patients who accept irrigation could be less likely to experience recurrence with a low dilatation grade and no branch duct dilatation.
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Although a variety of dynamic covalent bonds have been successfully used in the development of diverse sustainable thermosetting polymers and their composites, solving the trade-off between recovery efficiency and comprehensive properties is still a major challenge. Herein, a "one-stone-two-birds" strategy of lower rotational energy barrier (Er ) phosphate-derived Diels-Alder (DA) cycloadditions was proposed for easily recyclable carbon fiber (CF)-reinforced epoxy resins (EPs) composites. In such a strategy, the phosphate spacer with lower Er accelerated the segmental mobility and dynamic DA exchange reaction for network rearrangement to achieve high-efficiency repairing, reprocessing of the EPs matrix and its composites and rapid nondestructive recycling of CF; meanwhile, incorporating phosphorus-based units especially reduced their fire hazards. The resulting materials simultaneously showed excellent thermal/mechanical properties, superb fire safety and facile recyclability, realizing the concept of recycling for high-performance thermosetting polymers and composites. This strategy is of great significance for understanding and enriching the molecular connotation of DA chemistry, making it potentially applicable to the design and development of a wide range of dynamic covalent adaptable materials toward practical cutting-edge-tech applications.
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A novel oxidative cleavage and fluoromethylthiolation reaction of CâC bonds has been developed that represents the first and general method for the preparation of mono-, di-, and trifluoromethylthioesters from alkenes. The protocol features excellent product selectivity and substrate suitability. Various observations suggested that the protocol proceeded via a two-step radical process and that aldehyde was the key intermediate. What's more meaningful is that this route provides a new direction for converting alkenes into higher-value-added carbonyl-containing chemicals.