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The brain is a complex tissue whose function relies on coordinated anatomical and molecular features. However, the molecular annotation of the spatial organization of the brain is currently insufficient. Here, we describe microfluidic indexing-based spatial assay for transposase-accessible chromatin and RNA-sequencing (MISAR-seq), a method for spatially resolved joint profiling of chromatin accessibility and gene expression. By applying MISAR-seq to the developing mouse brain, we study tissue organization and spatiotemporal regulatory logics during mouse brain development.
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Cromatina , Sequenciamento de Nucleotídeos em Larga Escala , Animais , Camundongos , Cromatina/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de RNA , Encéfalo , Expressão Gênica , Perfilação da Expressão GênicaRESUMO
Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N-glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N-glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N-glycopeptides using recently developed site-specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N-glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.
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Vírus da Dengue , Dengue , Glicoproteínas , Proteômica , Humanos , Dengue/sangue , Dengue/virologia , Proteômica/métodos , Glicoproteínas/sangue , Glicosilação , Masculino , Feminino , Adulto , Proteoma/análise , Pessoa de Meia-IdadeRESUMO
Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.
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Exposição Materna , Mecônio , Material Particulado , Humanos , Feminino , Mecônio/química , Gravidez , Estudos de Coortes , Recém-Nascido , Adulto , Poluentes AtmosféricosRESUMO
The heat shock protein 70 (HSP70) gene family plays a crucial role in the response of organisms to environmental stress. However, it has not been systematically characterized in shrimp. In this study, we identified 25 PcHsp70 genes in the Penaeus chinensis genome. The encoded proteins were categorized into six subgroups based on phylogenetic relationships. Tandem duplication was the main driver of amplification in the PcHsp70 family, and the genes have experienced strong purifying selection during evolution. Transcriptome data analysis revealed that the 25 PcHsp70 members have different expression patterns in shrimp under conditions of low temperature, low salinity, and white spot syndrome virus infection. Among them, PcHsp70.11 was significantly induced under all three stress conditions, suggesting that this gene plays an important role in response to environmental stress in P. chinensis. To the best of our knowledge, this is the first study to systematically analyze the Hsp70 gene family in shrimp. The results provide important information on shrimp Hsp70s, contributing to a better understanding of the role of these genes in environmental stress and providing a basis for further functional studies.
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Proteínas de Choque Térmico HSP70 , Penaeidae , Filogenia , Estresse Fisiológico , Animais , Penaeidae/genética , Proteínas de Choque Térmico HSP70/genética , Estresse Fisiológico/genética , Família Multigênica/genética , Perfilação da Expressão Gênica , Transcriptoma , SalinidadeRESUMO
Objective: Exploring newer approaches to brachial plexus block is crucial for improving surgical outcomes and patient comfort. This study aims to review the application and research progress of ultrasound-guided brachial plexus block via the costoclavicular space approach in upper limb surgery. Methods: This study provides a comprehensive review of existing literature, studies, and clinical cases related to the costoclavicular approach. The advantages and disadvantages of conventional approaches for brachial plexus block, including the intermuscular groove method, supraclavicular method, and axillary approach, are discussed. The anatomical characteristics of the costoclavicular space are examined, and the methods of brachial plexus nerve block using ultrasound-guided costoclavicular space approach are described. It holds great promise for enhancing patient care and increasing the overall success rate of surgical procedures. Results: The costoclavicular space approach for brachial plexus block offers several advantages, including stable anatomical structure, low nerve variation rate, and clear visualization of each nerve bundle under ultrasound imaging. Compared to traditional approaches, ultrasound-guided brachial plexus block via the costoclavicular space approach has a high success rate, rapid onset of anesthesia, and high safety. Conclusion: Ultrasound-guided brachial plexus block via the costoclavicular space approach is effective and safe in upper limb surgery. It provides good anesthesia and postoperative analgesia, making it a valuable technique for various upper limb surgeries. The potential clinical significance of our findings lies in the possibility that ultrasound-guided costoclavicular space approach, with its enhanced precision and patient outcomes, could play a pivotal role in improving upper limb surgical procedures.
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Bloqueio do Plexo Braquial , Humanos , Bloqueio do Plexo Braquial/métodos , Anestésicos Locais , Ultrassonografia de Intervenção/métodos , Ultrassonografia , Extremidade Superior/cirurgiaRESUMO
BACKGROUND: Gastric cancer (GC) tumorigenesis and treatment failure are caused by cancer stem cells. Polypyrimidine tract binding protein 1 (PTBP1) was shown to be involved in the development of embryonic stem cells and is now being considered as a therapeutic target for tumour progression and stem-cell characteristics. METHODS: PTBP1 expression in GC samples was detected using tissue microarrays. Proliferation, colony formation, spheroid formation and stem-cell analysis were used to examine PTBP1's role in tumorigenesis and stem-cell maintenance. In AGS and HGC-27 cells with or without PTBP1 deficiency, ubiquitin-related protein expression and co-precipitation assays were performed. RESULTS: We identified that PTBP1 was aberrantly highly expressed and represented a novel prognostic factor in GC patients. PTBP1 maintained the tumorigenic activity and stem-cell characteristics of GC in vitro and in vivo. PTBP1 directly interacts with c-Myc and stabilises its protein levels by preventing its proteasomal degradation. This is mediated by upregulating the ubiquitin-specific proteases USP28 and limiting FBW7-mediated ubiquitination of c-Myc. Moreover, the depletion of PTBP1-caused tumour regression was significantly compromised by exogenous c-Myc expression. CONCLUSIONS: By preserving the stability of c-Myc through the ubiquitin-proteasome pathway, the oncogene PTBP1 supports stem-cell-like phenotypes of GC and is involved in GC progression.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Proliferação de Células/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Carcinogênese/genética , Ubiquitinas/metabolismo , Linhagem Celular Tumoral , Ubiquitina Tiolesterase/genética , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismoRESUMO
The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.
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COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Ácidos Nucleicos , Humanos , COVID-19/diagnóstico , Influenza Humana/diagnóstico , SARS-CoV-2/genética , Recombinases , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Sensibilidade e Especificidade , Nucleotidiltransferases , RNA , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/genéticaRESUMO
BACKGROUND: Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. METHODS: We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. RESULTS: Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. CONCLUSIONS: Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC.
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BACKGROUND: Trichinosis is a worldwide food-borne zoonotic parasitic disease, which is mainly obtained by ingesting undercooked meat containing infected larvae. The purpose of our article is to introduce and discuss two rare cases of pleural effusion caused by Trichinella spiralis. CASE PRESENTATION: Here we described two male patients who presented to the respiratory department of our hospital with a massive unilateral pleural effusion, their serum eosinophils were in the normal range, laboratory serological tests revealed that Trichinella spiralis IgG antibody was positive. After the oral administration of antiparasitic drugs, the pleural effusion of two patients was completely absorbed. CONCLUSION: Both patients were diagnosed with Trichinosis complicated with pleural effusion, which is very rare in the clinic and easy to be misdiagnosed because of normal eosinophils.
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Derrame Pleural , Trichinella spiralis , Triquinelose , Animais , Humanos , Masculino , Triquinelose/complicações , Triquinelose/diagnóstico , Triquinelose/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Carne/parasitologia , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Anticorpos Anti-Helmínticos , LarvaRESUMO
Based on Au nano-cone array (Au-NCA) and a three-segment hybridization strategy, a novel SERS biosensor is proposed for the ultrasensitive detection of the microRNA miR-21. The uniform, stable, and reproducible Au-NCA was prepared by the single-layer colloidal ball template method. Subsequently, the target was hybridized with sequence 2. The resulting target-sequence 2 complex was then hybridized with sequence 1 anchored on Au-NCA. Thus, a three-segment sequence complex was formed. SERS measurements can be performed without the need for complex purification and amplification steps. Due to the ability of miR-21 to perform specific complementary hybridization with two sequences, SERS biosensors have superior specificity for miR-21 without interference from other miRNAs. Under the optimal conditions, the SERS biosensor was applied and the limit of detection (LOD) was as low as 3.02 aM. This method has been successfully used to the detection of miR-21 in the serum of lymphoma patients and healthy volunteers. The results are consistent with the traditional test methods. Therefore, this novel SERS biosensor shows excellent clinical translational potential in the detection of lymphoma.
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Nanopartículas Metálicas , MicroRNAs , Humanos , Análise Espectral Raman/métodos , Ouro , Hibridização de Ácido NucleicoRESUMO
Background: Catheter-related infection (CRI) is a major complication in patients undergoing hemodialysis. The lack of high-throughput research on catheter-related microbiota makes it difficult to predict the occurrence of CRI. Thus, this study aimed to delineate the microbial structure and diversity landscape of hemodialysis catheter tips among patients during the perioperative period of kidney transplantation (KTx) and provide insights into predicting the occurrence of CRI.Methods: Forty patients at the Department of Transplantation undergoing hemodialysis catheter removal were prospectively included. Samples, including catheter tip, catheter outlet skin swab, catheter blood, peripheral blood, oropharynx swab, and midstream urine, from the separate pre- and post-KTx groups were collected and analyzed using metagenomic next-generation sequencing (mNGS). All the catheter tips and blood samples were cultured conventionally.Results: The positive detection rates for bacteria using mNGS and traditional culture were 97.09% (200/206) and 2.65% (3/113), respectively. Low antibiotic-sensitivity biofilms with colonized bacteria were detected at the catheter tip. In asymptomatic patients, no statistically significant difference was observed in the catheter tip microbial composition and diversity between the pre- and post-KTx group. The catheter tip microbial composition and diversity were associated with fasting blood glucose levels. Microorganisms at the catheter tip most likely originated from catheter outlet skin and peripheral blood.Conclusions: The long-term colonization microbiota at the catheter tip is in a relatively stable state and is not readily influenced by KTx. It does not act as the source of infection in all CRIs, but could reflect hematogenous infection to some extent.
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Infecções Relacionadas a Cateter , Transplante de Rim , Microbiota , Humanos , Transplante de Rim/efeitos adversos , Estudos Transversais , Cateteres de Demora/efeitos adversos , Infecções Relacionadas a Cateter/diagnóstico , Diálise Renal/efeitos adversosRESUMO
PURPOSE: This review aimed to conduct a meta-analysis of published randomized controlled studies (RCTs) comparing the effectiveness of dexmedetomidine (DEX) combined with ropivacaine versus single ropivacaine in transversus abdominis plane block (TAPB) for postoperative analgesia after laparoscopic cholecystectomy (LC). The purpose was to investigate whether DEX combined with ropivacaine in TAPB for postoperative analgesia in LC is superior to single ropivacaine administration. DESIGN: A Systematic Review and Meta-analysis. METHODS: Five electronic database systems were searched for RCTs on the effects of DEX combined with ropivacaine (joint group) and single ropivacaine on postoperative analgesia in LC. The standardized mean difference (SMD) or odds ratio (OR) and their corresponding 95% confidence interval (CI) of the indicators were calculated for comparison. FINDINGS: As of December 23, 2021, 153 articles were retrieved, but only 16 articles were finally included in this meta-analysis. The results showed that compared with single ropivacaine, DEX combined with ropivacaine in TAPB had better analgesia and lighter sedative effect in patients after LC. After LC 2h(T1), 4h(T2), 8h(T3), 12h(T4) and 24h (T5), the joint group participants have lower VAS scores (T1: SMD = -0.32, 95%CI: -0.49, -0.14; T2: SMD = -1.11, 95%CI: -1.56, -0.65; T3: SMD = -2.88, 95%CI: -3.74, -2.02; T4: SMD = -2.56, 95%CI: -3.04, -2.08; T5: SMD = -1.44, 95%CI: -1.81, -1.06). Also, the Ramsay score of the joint group is higher than the single group (T1: SMD = 1.05, 95%CI: 0.39, 1.71; T2: SMD = 1.57, 95%CI: 0.57, 2.57; T3: SMD = 1.64, 95%CI: 0.65, 2.63; T4: SMD = 1.72, 95%CI: 0.54, 2.89; T5: SMD = 0.57, 95%CI: 0.21, 0.94). CONCLUSIONS: The results of this review and meta-analysis suggest that DEX combined with ropivacaine has less postoperative pain, more patients got the status of sober and cooperative, and longer postoperative analgesia lasted than ropivacaine alone in TAPB, especially in the group of combined treatment with 1.0 mcg/kg DEX. Furthermore, the flow dynamics of the two groups are stable, and there is no notable difference in the incidence of adverse reactions.
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Colecistectomia Laparoscópica , Dexmedetomidina , Humanos , Ropivacaina/farmacologia , Colecistectomia Laparoscópica/efeitos adversos , Anestésicos Locais , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Músculos Abdominais , AnalgésicosRESUMO
The combination of carbon-based nanohoops with other functional organic molecular structures should lead to the design of new molecular configurations with interesting properties. Here, necklace-like nanohoops embedded with carborane were synthesized for the first time. The unique deboronization of o-carborane has led to the facile preparation of ionic nanohoop compounds. Nanohoops functionalized by nido-o-carborane show excellent fluorescence emission, with a solution quantum yield of up to 90.0 % in THF and a solid-state quantum efficiency of 87.3 %, which opens an avenue for the applications of the nanohoops in OLEDs and bioimaging.
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Boranos , Boro , Estrutura Molecular , Compostos de Boro , Boranos/químicaRESUMO
The layout of portable document format (PDF) files is constant to any screen, and the metadata therein are latent, compared to mark-up languages such as HTML and XML. No semantic tags are usually provided, and a PDF file is not designed to be edited or its data interpreted by software. However, data held in PDF files need to be extracted in order to comply with open-source data requirements that are now government-regulated. In the chemical domain, related chemical and property data also need to be found, and their correlations need to be exploited to enable data science in areas such as data-driven materials discovery. Such relationships may be realized using text-mining software such as the "chemistry-aware" natural-language-processing tool, ChemDataExtractor; however, this tool has limited data-extraction capabilities from PDF files. This study presents the PDFDataExtractor tool, which can act as a plug-in to ChemDataExtractor. It outperforms other PDF-extraction tools for the chemical literature by coupling its functionalities to the chemical-named entity-recognition capabilities of ChemDataExtractor. The intrinsic PDF-reading abilities of ChemDataExtractor are much improved. The system features a template-based architecture. This enables semantic information to be extracted from the PDF files of scientific articles in order to reconstruct the logical structure of articles. While other existing PDF-extracting tools focus on quantity mining, this template-based system is more focused on quality mining on different layouts. PDFDataExtractor outputs information in JSON and plain text, including the metadata of a PDF file, such as paper title, authors, affiliation, email, abstract, keywords, journal, year, document object identifier (DOI), reference, and issue number. With a self-created evaluation article set, PDFDataExtractor achieved promising precision for all key assessed metadata areas of the document text.
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Metadados , Leitura , Mineração de Dados , Processamento de Linguagem Natural , SoftwareRESUMO
SIGNIFICANCE: Sarcoidosis is a variable, multisystem granulomatous disease, which can affect many organs including the lungs, lymph nodes, and eyes. It is difficult to differentiate sarcoidosis and tuberculosis because of their similar clinical and pathological features. PURPOSE: This study aimed to describe a sarcoidosis case with typical ocular and systemic manifestations combined with suspected tuberculosis infection. CASE REPORT: A 30-year-old Chinese man, initially diagnosed with tuberculosis, presented with typical ocular sarcoidosis during antituberculosis therapy. The ocular surface, anterior chamber, anterior chamber angle, ciliary body, vitreous, optic disc, and lacrimal gland of the patient all exhibited manifestations of sarcoidosis, although optic disc involvement has rarely been reported. Typical ocular sarcoidosis manifestations and positive responses to corticosteroid therapy of the patient helped us reach the diagnosis of systemic sarcoidosis. The patient was followed up for 48 months and showed significant improvement of miliary nodules and lymph nodes in both lungs. However, the appearance of uveitis in the right eye persisted because of nonadherence to steroid treatment. CONCLUSIONS: This case shows the importance of ophthalmic evaluation in the diagnosis and management of sarcoidosis and supports a possible role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis.
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Sarcoidose , Uveíte , Adulto , Biópsia/efeitos adversos , Diagnóstico Diferencial , Granuloma/diagnóstico , Humanos , Masculino , Sarcoidose/diagnóstico , Uveíte/diagnóstico , Uveíte/etiologiaRESUMO
Gastric cancer is a type of malignant tumor that seriously threatens human life and health. Invasion and metastasis present difficulties in the treatment of gastric cancer, and the remodeling of the tumor cytoskeleton plays an important role in mediating the ability of tumor cells to achieve invasion and metastasis. Previous experimental results suggest that Celastrus orbiculatus extract can regulate cytoskeletal remodeling in gastric cancer, but the active component has not been determined. Betulonic acid, as an effective component of COE, inhibits the invasion and metastasis of gastric cancer cells by regulating cytoskeletal remodeling in vitro; its specific mechanisms have been studied here. After betulonic acid was dissolved, it was diluted to various working concentrations in RPMI-1640 medium and added to AGS, HGC-27 and GES-1 cell lines. Cell viability was assessed by CCK-8 and colony formation assays. Cytoskeleton staining was used to detect changes in cytoskeleton morphology. Functional assays including wound healing assays and transwell assays were used to detect the invasion and migration of cells. The effect of betulonic acid on cell invasion and migration was clearly and precisely observed by high-content imaging technology. Western blotting was used to detect the regulation of matrix metalloproteinase-related proteins and epithelial-mesenchymal transformation-related proteins. We found that betulonic acid inhibited the migration and invasion of gastric cancer cells. Therefore, betulonic acid inhibits the invasion and metastasis of gastric cancer cells by mediating cytoskeletal remodeling and regulating epithelial mesenchymal transformation.
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Antineoplásicos Fitogênicos/farmacologia , Celastrus , Citoesqueleto/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Ácido Oleanólico/análogos & derivados , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Celastrus/química , Linhagem Celular Tumoral , Citoesqueleto/patologia , Humanos , Invasividade Neoplásica/patologia , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Ferulic acid (FA), a phenolic acid widely occurring in nature, has attracted extensive attention because of its biological activity. Ovalbumin (OVA) is a commonly used carrier protein. The mechanism of FA binding with OVA was investigated by utilizing a variety of spectral analyses, accompanied by computer simulation. RESULTS: It was discovered that the fluorescence quenching mechanism of OVA by FA was a static mode as a result of the formation of an FA-OVA complex, which was verified by the concentration distributions and pure spectrum of the constituents decomposed from the high overlap spectrum signals using multivariate curve resolution-alternate least squares algorithm. Hydrogen bonds and Van der Waals forces drove the formation of FA-OVA complex with a binding constant of 1.69 × 104 L mol-1 . The presence of FA induced the loose structure of OVA with an attenuation of α-helix content and improved the thermal stability of OVA. Computer docking indicated that FA interacted with the amino acid residues Arg84, Asn88, Leu101 and Ser103 of OVA through hydrogen bonds. Molecular dynamics simulation proved that the combination of FA with OVA boosted the conformational stability of OVA and hydrogen bonds brought a crucial part in stabilizing the structure of the complex. CONCLUSIONS: The study may supply the theoretical basis for the design of FA transport system using OVA as carrier protein to improve the instability and low bioavailability of FA. © 2021 Society of Chemical Industry.
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Proteínas de Transporte , Simulação de Dinâmica Molecular , Sítios de Ligação , Proteínas de Transporte/metabolismo , Simulação por Computador , Ácidos Cumáricos , Simulação de Acoplamento Molecular , Ovalbumina/química , Ligação Proteica , Espectrometria de Fluorescência , Análise Espectral , TermodinâmicaRESUMO
BACKGROUND: Tea polyphenols have been reported to have the effect of lowering uric acid. However, there are few studies on the inhibitory effects and molecular mechanisms of specific catechins on the urate-metabolizing enzyme xanthine oxidase (XO). In this research, multiple spectroscopic methods and computer simulations were used to determine the inhibitory ability and mechanisms of epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG) on XO. RESULTS: Herein, EGCG and GCG reversibly inhibited XO activity in a mixed manner, with IC50 values of 40.50 ± 0.32 and 33.60 ± 0.53 µmol L-1 , and also decreased the superoxide anion radical (O2 - ) of the catalytic system by reducing the XO molecule and inhibiting the formation of uric acid. The combination of EGCG or GCG with allopurinol showed synergistic inhibition on XO. The binding of EGCG or GCG to XO with moderate affinity formed a stable complex by hydrogen bonds and van der Waals forces. The presence of EGCG and GCG made the structure of XO more stable and compact. The two inhibitors bound to the vicinity of flavin adenine dinucleotide (FAD) in XO, hindering the entry of substrate; thus the activity of XO was suppressed. CONCLUSION: Both EGCG and GCG are excellent natural XO inhibitors, and inhibited the activity of XO by occupying the channel of the substrate to enter the active center and interfering with the dual substrate reaction catalyzed by XO. These findings provide a scientific basis for the application of catechins in dietary supplements and medicines with lowering uric acid effects. © 2022 Society of Chemical Industry.
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Alopurinol , Xantina Oxidase , Xantina Oxidase/metabolismo , Polifenóis , Ácido Úrico , Inibidores Enzimáticos/química , CháRESUMO
BACKGROUND: Although energy devices and botulinum toxin A (BTX-A) can alleviate age-related laxity, ptosis, and platysmal bands, they have limited efficacy on horizontal neck lines. OBJECTIVES: The purpose of this study was to investigate the efficacy, safety, and subject satisfaction of a combined treatment of non-cross-linked hyaluronic acid (HA) compound filling plus mesotherapy for the correction of horizontal neck lines, in comparison with BTX-A. METHODS: This multicenter, randomized, evaluator-blinded, prospective study enrolled female patients with moderate-to-severe horizontal neck lines corrected with either 2 or 3 sessions of of non-cross-linked HA compound filling plus mesotherapy or 1 session of BTX-A injection. Improvement of the neck lines grades, Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and adverse events (AEs) were evaluated and compared at 1, 3, 6, and 10 months after the final treatment. RESULTS: Twenty-five patients received HA filling plus mesotherapy and 23 received BTX-A injection. Compared with BTX-A, the HA compound filling plus mesotherapy significantly improved the horizontal neck lines grades on all follow-up visits (Pâ =â 0.000). Cases of different baseline grades (2, 2.5, and 3) demonstrated similar outcomes. The GAIS and patients' satisfaction ratings were significantly higher for the HA filling plus mesotherapy treatment group (Pâ =â 0.000). Significantly higher pain ratings, higher incidence, and longer recovery of AEs (erythema, edema, and ecchymosis) were noticed in the combined treatment group (Pâ <â 0.001). No serious AEs occurred. CONCLUSIONS: Compared with BTX-A, combined treatment with HA compound filling plus mesotherapy significantly improved moderate-to-severe horizontal neck lines and achieved a high level of patient satisfaction.
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Toxinas Botulínicas Tipo A , Técnicas Cosméticas , Mesoterapia , Envelhecimento da Pele , Toxinas Botulínicas Tipo A/efeitos adversos , China , Técnicas Cosméticas/efeitos adversos , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Estudos Prospectivos , Resultado do TratamentoRESUMO
We developed o-carborane as a new mechanophore by showing that the o-carborane cluster is the preferred scission site in chain-centered polymers through ultrasonication mechanochemistry. Mechanistic studies are consistent with a predominately homolytic mechanism of chain scission. The mechanically generated monocarbaborane fragments are highly reactive toward alcohol nucleophiles. By contrast, carborane with a different regiochemistry (m-carborane) maintained its high mechanical stability. DFT simulations provide insights into the origins of carborane's mechanical lability. This fundamental research provides a new stimulus for carborane cage activation.