RESUMEN
Primary liver cancer is one of the leading causes of cancer-related deaths worldwide, its early diagnosis and early treatment are of great clinical importance. The main detection tools for liver cancer include serological indicators, imaging tests and risk assessment models. With the advancement of technology and research, the sensitivity and specificity of laboratory tests for liver cancer have been substantially improved, but there are still false negatives and low rates of early diagnosis. For different causes and prevalence regions, each country has developed its clinical practice guidelines to guide risk groups for effective prevention, early diagnosis and standardized treatment. It is important to establish a liver cancer diagnosis strategy that is suitable for China's national conditions, concerning the guidelines for the vigilance and prevention of liver cancer. In this article, the advantages and disadvantages of liver cancer-related tests and the impact of future development trends on laboratory strategies are explained from the perspective of laboratory testing strategies, to provide theoretical support for the practical application of liver cancer diagnostic strategies.
Asunto(s)
Humanos , Sensibilidad y Especificidad , Factores de Riesgo , Medición de Riesgo , Neoplasias Hepáticas/diagnósticoRESUMEN
Primary liver cancer is one of the leading causes of cancer-related deaths worldwide, its early diagnosis and early treatment are of great clinical importance. The main detection tools for liver cancer include serological indicators, imaging tests and risk assessment models. With the advancement of technology and research, the sensitivity and specificity of laboratory tests for liver cancer have been substantially improved, but there are still false negatives and low rates of early diagnosis. For different causes and prevalence regions, each country has developed its clinical practice guidelines to guide risk groups for effective prevention, early diagnosis and standardized treatment. It is important to establish a liver cancer diagnosis strategy that is suitable for China's national conditions, concerning the guidelines for the vigilance and prevention of liver cancer. In this article, the advantages and disadvantages of liver cancer-related tests and the impact of future development trends on laboratory strategies are explained from the perspective of laboratory testing strategies, to provide theoretical support for the practical application of liver cancer diagnostic strategies.
Asunto(s)
Humanos , Sensibilidad y Especificidad , Factores de Riesgo , Medición de Riesgo , Neoplasias Hepáticas/diagnósticoRESUMEN
Objective: To establish a comprehensive diagnostic classification model of lateral cephalograms based on artificial intelligence (AI) to provide reference for orthodontic diagnosis. Methods: A total of 2 894 lateral cephalograms were collected in Department of Orthodontics, Capital Medical University School of Stomatology from January 2015 to December 2021 to construct a data set, including 1 351 males and 1 543 females with a mean age of (26.4± 7.4) years. Firstly, 2 orthodontists (with 5 and 8 years of orthodontic experience, respectively) performed manual annotation and calculated measurement for primary classification, and then 2 senior orthodontists (with more than 20 years of orthodontic experience) verified the 8 diagnostic classifications including skeletal and dental indices. The data were randomly divided into training, validation, and test sets in the ratio of 7∶2∶1. The open source DenseNet121 was used to construct the model. The performance of the model was evaluated by classification accuracy, precision rate, sensitivity, specificity and area under the curve (AUC). Visualization of model regions of interest through class activation heatmaps. Results: The automatic classification model of lateral cephalograms was successfully established. It took 0.012 s on average to make 8 diagnoses on a lateral cephalogram. The accuracy of 5 classifications was 80%-90%, including sagittal and vertical skeletal facial pattern, mandibular growth, inclination of upper incisors, and protrusion of lower incisors. The acuracy rate of 3 classifications was 70%-80%, including maxillary growth, inclination of lower incisors and protrusion of upper incisors. The average AUC of each classification was ≥0.90. The class activation heat map of successfully classified lateral cephalograms showed that the AI model activation regions were distributed in the relevant structural regions. Conclusions: In this study, an automatic classification model for lateral cephalograms was established based on the DenseNet121 to achieve rapid classification of eight commonly used clinical diagnostic items.
Asunto(s)
Masculino , Femenino , Humanos , Adulto Joven , Adulto , Inteligencia Artificial , Aprendizaje Profundo , Cefalometría , Maxilar , Mandíbula/diagnóstico por imagenRESUMEN
Objective: To develop a multi-classification orthodontic image recognition system using the SqueezeNet deep learning model for automatic classification of orthodontic image data. Methods: A total of 35 000 clinical orthodontic images were collected in the Department of Orthodontics, Capital Medical University School of Stomatology, from October to November 2020 and June to July 2021. The images were from 490 orthodontic patients with a male-to-female ratio of 49∶51 and the age range of 4 to 45 years. After data cleaning based on inclusion and exclusion criteria, the final image dataset included 17 453 face images (frontal, smiling, 90° right, 90° left, 45° right, and 45° left), 8 026 intraoral images [frontal occlusion, right occlusion, left occlusion, upper occlusal view (original and flipped), lower occlusal view (original and flipped) and coverage of occlusal relationship], 4 115 X-ray images [lateral skull X-ray from the left side, lateral skull X-ray from the right side, frontal skull X-ray, cone-beam CT (CBCT), and wrist bone X-ray] and 684 other non-orthodontic images. A labeling team composed of orthodontic doctoral students, associate professors, and professors used image labeling tools to classify the orthodontic images into 20 categories, including 6 face image categories, 8 intraoral image categories, 5 X-ray image categories, and other images. The data for each label were randomly divided into training, validation, and testing sets in an 8∶1∶1 ratio using the random function in the Python programming language. The improved SqueezeNet deep learning model was used for training, and 13 000 natural images from the ImageNet open-source dataset were used as additional non-orthodontic images for algorithm optimization of anomaly data processing. A multi-classification orthodontic image recognition system based on deep learning models was constructed. The accuracy of the orthodontic image classification was evaluated using precision, recall, F1 score, and confusion matrix based on the prediction results of the test set. The reliability of the model's image classification judgment logic was verified using the gradient-weighted class activation mapping (Grad-CAM) method to generate heat maps. Results: After data cleaning and labeling, a total of 30 278 orthodontic images were included in the dataset. The test set classification results showed that the precision, recall, and F1 scores of most classification labels were 100%, with only 5 misclassified images out of 3 047, resulting in a system accuracy of 99.84%(3 042/3 047). The precision of anomaly data processing was 100% (10 500/10 500). The heat map showed that the judgment basis of the SqueezeNet deep learning model in the image classification process was basically consistent with that of humans. Conclusions: This study developed a multi-classification orthodontic image recognition system for automatic classification of 20 types of orthodontic images based on the improved SqueezeNet deep learning model. The system exhibitted good accuracy in orthodontic image classification.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Aprendizaje Profundo , Reproducibilidad de los Resultados , Radiografía , Algoritmos , Tomografía Computarizada de Haz CónicoRESUMEN
This study explored the effect and underlying mechanism of Stellera chamaejasme extract(SCE) on multidrug resistance of breast cancer. The chemotherapy-sensitive breast cancer cell line MCF-7 and adriamycin(ADR)-resistant cell line MCF-7/ADR were used as experimental subjects. MTT assay was used to detect cell proliferation activity. Pi staining was used to detect the cell cycle. 4',6-Diamidino-2-phenylindole, dihydrochloride(DAPI) staining and flow cytometry were used to detect apoptosis. Dansylcadaverine(MDC) staining and GFP-LC3B-Mcherry adenovirus transfection were used to detect autophagy. The protein expression of Bcl-2, Bax, caspase-9, caspase-3, LC3B, p62, and Beclin-1 was detected by Western blot. The results showed that SCE could significantly inhibit the proliferation of both sensitive and resistant breast cancer cell lines. The drug resistance factor was 0.53, which was significantly lower than 59 of ADR. Meanwhile, the proportion of sensitive/resistant cells in the G_0/G_1 phase increased significantly after SCE treatment. In addition, DAPI staining showed that a series of apoptosis phenomena such as nuclear pyknosis, staining deepening, and nuclear fragmentation appeared in sensitive/resistant cell lines after SCE administration. Moreover, the results of flow cytometry double staining showed that the proportion of apoptotic cells in sensitive/resistant cell lines increased significantly after SCE administration. Besides, Western blot showed that the protein expression levels of caspase-3, caspase-9, and Bcl-2 significantly decreased and the expression level of Bax protein significantly increased in both breast cancer cell lines after SCE administration. Furthermore, SCE could also increase the positive fluorescent spots after MDC staining and yellow fluorescent spots after GFP-LC3B-mcherry transfection, and up-regulate the expression levels of autophagy-related proteins LC3B-Ⅱ, p62, and Beclin-1 in breast cancer cells. In summary, SCE may play the role of anti-multidrug resistance by blocking the cell cycle of breast cancer multidrug-resistant cells, blocking autophagy flow, and ultimately interfering with the apoptosis resistance of drug-resistant cells.
Asunto(s)
Humanos , Femenino , Neoplasias de la Mama/metabolismo , Células MCF-7 , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Beclina-1/farmacología , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Línea Celular Tumoral , Resistencia a Antineoplásicos , Proliferación CelularRESUMEN
OBJECTIVE@#To investigate the expression and prognostic value of cytokines in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).@*METHODS@#Clinical data of 62 patients diagnosed with DLBCL in the First People's Hospital of Yunnan Province from June 2017 to November 2018 were collected. The differences in expression levels of 14 serum cytokines [interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-β] in patients with different survival outcomes, and the impact of the cytokines on 3-year progression-free survival (PFS) and 3-year overall survival (OS) of patients with DLBCL were analyzed retrospectively.@*RESULTS@#Among the 14 cytokines, only the expression of IL-10 was significantly different in patients with different survival outcomes (P =0.007). According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for IL-10 was 11.74 pg/ml. Serum IL-10 was positively correlated with infection markers procalcitonin (PCT) (r =0.321, P =0.029), C-reactive protein (CRP) (r =0.320, P =0.013) and tumor burden index lactate dehydrogenase (LDH) (r =0.439, P <0.001) in newly diagnosed DLBCL patients. The level of IL-10 in patients with pulmonary infection was significantly higher than that in patients without pulmonary infection (P =0.012). However, there was no statistically significant difference on the 3-year survival outcomes between patients with or without pulmonary infection. There was no significant difference in IL-10 level in patients with different Ann Arbor stages (P >0.05). Patients with high IL-10 level (IL-10>11.74 pg/ml) had significantly higher LDH level than those with low IL-10 level (IL-10≤11.74 pg/ml) (P <0.001). The 3-year PFS rate and 3-year OS rate of DLBCL patients with high IL-10 level were significantly lower than those of low IL-10 level group [(44.4±11.7)% vs (81.8±5.8)%, P <0.001; (61.6±11.5)% vs (93.2±3.8)%, P =0.001].@*CONCLUSION@#Serum IL-10 level in newly diagnosed DLBCL patients can reflect the inflammatory state of the body, which may be related to tumor load. Newly diagnosed DLBCL patients with serum IL-10>11.74 pg/ml have higher early mortality and worse prognosis.
Asunto(s)
Humanos , Pronóstico , Citocinas , Interleucina-10 , Estudios Retrospectivos , China , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Factor de Necrosis Tumoral alfa , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
Hazardous industrial wastes negatively impact the environment by creating issues for aquatic as well as human's life. This study investigates the treatment of hazardous industrial wastewater using cost-effective graphite adsorbent along with electrochemical regeneration integrated with renewable solar energy. The synthetic industrial effluent containing crystal violet dye was treated using an adsorbent (Nyex™ 1000) having a surface area of 1.0 m2 g-1 . The efficiency of removing solute was found to be more than 90%. The adsorbent regeneration efficiency was achieved at 99.5% by passing a charge of 100 C g-1 at current density of 10 mA cm-2 for 1 h. Solar energy was integrated with electrochemical reactor for the regeneration of adsorbent to make the system cost-effective and self-sustainable. PRACTITIONER POINTS: Industrial hazardous wastewater treatment with a cost-effective graphite integrated adsorbent. Development of renewable solar energy-integrated with electrochemical system for regeneration. Regeneration efficiency of adsorbent Nyex™ 1000 was achieved around 99.5% with integrated system. Sustainable system was introduced to incorporate with renewable energy for waste water treatment.
Asunto(s)
Grafito , Energía Solar , Purificación del Agua , Humanos , Aguas ResidualesRESUMEN
This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.
Asunto(s)
Apoptosis , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Extractos Vegetales , Transducción de Señal , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Objective:To establish an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration, and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome (CVH-IBS). Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty (PTCA) balloon stimulation method. After intragastric administration of Wujiwan (0.245 g·kg<sup>-1</sup>), blood was collected from the jugular vein at different time points, and the plasma concentrations of 10 active ingredients (berberine hydrochloride, palmatine hydrochloride, coptisine hydrochloride, jatrorrhizine hydrochloride, epiberberine, dihydroberberine, evodiamine, evodine, paeoniflorin, albiflorin) in Wujiwan was detected simultaneously by UPLC-MS/MS, the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated. Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group, the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent, and the peak time (<italic>t</italic><sub>max</sub>) was prolonged. Among them, the <italic>t</italic><sub>max</sub> of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute, respectively (<italic>P</italic><0.05, <italic>P</italic><0.01). Area under the plasma concentration-time curve (AUC<sub>0-</sub><italic><sub>t</sub></italic>) of each component increased, and evodiamine and paeoniflorin were significantly different (<italic>P</italic><0.05,<italic> P</italic><0.01). The clearance rates (CL/<italic>F</italic>) of these 10 active ingredients were all decreased, among which berberine hydrochloride, palmatine hydrochloride and evodiamine had significant differences (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats, which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.
RESUMEN
Objective:To analyze active components, its targets and signaling pathways of Shenlian formula based on network pharmacology, and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease (ASCVD), in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine (TCMSP), its target proteins were obtained by SymMap and ETCM Databases, and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions (PPI) network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds, 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 (PTGS2), estrogen receptor 1 (ESR1) and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic, nitric oxide biosynthetic process, response to estradiol, angiogenesis, inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway, phosphatidylinositol-3 kinase (PI3K)/ protein kinase B (Akt) signaling pathway, hypoxia induction factor-1 (HIF-1) signaling pathway and apoptosis. Among them, the regulatory effect of Shenlian formula on apoptosis may act on not only TP53, but also different signaling pathways of apoptosis respectively, thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area, improve the myocardial histopathological changes, and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD, and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.
RESUMEN
Objective:To compare the therapeutic efficacies of Wujiwan at two different compatibilities (No.1 and No.2) on irritable bowel syndrome (IBS) based on neuro-endocrine-immune network, and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine (TCM). Method:The chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty (PTCA) in suckling rats. The animals were randomly divided into a control group, a model group, a dicetel group (0.01 g·kg<sup>-1</sup>), low- (0.335 g·kg<sup>-</sup><bold><sup>1</sup></bold>), medium- (0.67 g·kg<sup>-</sup><bold><sup>1</sup></bold>), and high-dose (1.34 g·kg<sup>-</sup><bold><sup>1</sup></bold>) No. 1 Wujiwan groups, and low- (0.385 g·kg<sup>-</sup><bold><sup>1</sup></bold>), medium- (0.77 g·kg<sup>-</sup><bold><sup>1</sup></bold>), and high-dose (1.54 g·kg<sup>-</sup><bold><sup>1</sup></bold>) No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells (MC) in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine (5-HT), substance P (SP), somatostatin (SS), and vasoactive intestinal peptide (VIP) in the blood/colon tissue were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assay. Result:There was no significant difference in body weight among different groups. Compared with the control group, the model group exhibited decreased thresholds of abdominal elevation and bow back elevation (<italic>P<</italic>0.01), increased density of MCs in the colon tissue (<italic>P<</italic>0.05), up-regulated levels of 5-HT, SP, and SS in the blood and colon tissue (<italic>P<</italic>0.05, <italic>P<</italic>0.01), and elevated VIP level in the colon tissue (<italic>P</italic><0.05). Compared with the model group, Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation (<italic>P</italic><0.01), diminish the count of MC in the colon tissue (<italic>P</italic><0.05), and reduce the levels of 5-HT, SP, SS, and VIP (<italic>P</italic><0.05). As demonstrated by the comparison of No. 1 and No. 2 Wujiwan, No. 1 was superior to No. 2 in reducing the concentrations of 5-HT, SP, and SS in the blood, especially in 5-HT (<italic>P</italic><0.01). No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan, No. 2 significantly reduced SP expression, and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups (<italic>P</italic><0.05). Conclusion:Wujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect, No. 1 was superior to No. 2, while in terms of local effect, No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics, while No. 2 had an advantageous effect on intestinal sensation over No. 1.
RESUMEN
ObjectiveTo explore the value of MSCT for differentiating the hypovascular pancreatic neuroendocrine tumors (Hypo-PNETs) from mass-forming pancreatitis.Methods21 patients with histological-confirmed MPFs and 19 patients with Hypo-PNETs who underwent preoperative dynamic contrast-enhanced CT were included. The CT images were analyzed including tumor size,density, border, CT values in each phase, dilatation of pancreatic duct and bile duct and metastases. The clinical data included age, sex and clinical symptoms.ResultsMFPs often occurred in male patient compared with Hypo-PNETs (85.7% vs 52.6%, P<0.05), and the difference is statistically significant; Metastases only occurred in Hypo-PNETs (P<0.05), and the difference is drastically significant. The well-defined margin often occurred in Hypo-PNETs (52.4% vs 47.6%, P=0.032). Solid tumor more happened in MFPs(95.2% vs 47.4%, P<0.05). The CT values in the portal of MFPs were higher than Hypo-PNETs(P<0.05). The combined features showed accepted diagnostic performance for differentiating Hypo-PNETs from MFPs (89.5% of sensitivity and 95.2% of specificity).ConclusionMFPs often occurred in male patient, and CT values of portal phase, density, border and metastases may be valuable for differentiating Hypo-PNETs from MFPs.
RESUMEN
Corona virus disease 2019(COVID-19) has brought untold human sufferings and economic tragedy worldwide. It causes acute myocardial injury and chronic damage of cardiovascular system, which has attracted much attention from researchers. For the immediate strategy for COVID-19, "drug repurposing" is a new opportunity for developing drugs to fight COVID-19. Artemisinin and its derivatives have a wide range of pharmacological activities. Recent studies have shown that artemisinin has clear cardiovascular protective effects. This paper summarizes the research progress on the pathogenesis the pathogenesis of COVID-19 in cardiovascular damage by 2019 novel coronavirus(2019-nCoV) virus from myocardial cell injury directly by 2019-nCoV virus,viral ligands competitively bind to ACE2 and then reduce the protective effect of ACE2 on cardiovascular disease, "cytokine storm" related myocardial damage, arrhythmia and sudden cardiac death induced by the infection and stress, myocardial injury by hypoxemia, heart damage side effects from COVID-19 drugs and summarizing the cardiovascular protective effects of artemisinin and its derivatives have activities of anti-arrhythmia, anti-myocardial ischemia, anti-atherosclerosis and plaque stabilization. Then analyzed the possible multi-pathway intervention effects of artemisinin-based drugs on multiple complications of COVID-19 based on its specific immunomodulatory effects, protective effects of tissue and organ damage and broad-spectrum antiviral effect, to provide clues for the treatment of cardiovascular complications of COVID-19, and give a new basis for the therapy of COVID-19 through "drug repurposing".
Asunto(s)
Humanos , Artemisininas , COVID-19 , Enfermedades Cardiovasculares , Cardiopatías , SARS-CoV-2RESUMEN
The normal immune system has the ability to distinguish between "self" and "non-self". Because of its dynamic balance of "immune activity-immune tolerance", it will produce immune response to the non-self antigen, but with no response or weak response to the self-antigen. However, if the balance was broken, T cell in the abnormal immune activation state will respond continually to the self-antigen, with an abnormal immune response, which caused autoimmune disease. Pathologically, "invalid" immune recognition and immune response become the main causes for autoimmune diseases. Co-stimulatory molecule is an important link between Attach antigen presenting cells(APC) and immune cells (T cell and B cell). Studies have proved that excessive co-stimulation and/or insufficient co-inhibition could cause detect of self-tolerance and induce autoimmunity. Although co-stimulatory and co-inhibitory pathways have a significant impact on all ADS, this paper focuses on their effect on two systemic autoimmune diseases [systemic lupus erythematosus (SLE) and rheumatoid arthritis(RA)] and two organ-specific autoimmune diseases [multiple sclerosis (MS) and type 1 diabetes (T1DM)], in order to discuss the pathogenesis and relationship between co-stimulatory molecules and autoimmune diseases.
RESUMEN
Objective:By means of network pharmacology, the active ingredients, targets and molecular pathways of Shengmaiyin (Dangshen prescription) in the treatment of atherosclerotic cardiovascular disease (ASCVD) were studied, in order to reveal the molecular mechanism of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD, and provide the rational explanation of the compatibility of the combination. Method:The main chemical components of Shengmaiyin (Dangshen prescription) were obtained by means of SymMap database, traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)platform and BATMAN-TCM platform. Compound targets were retrieved by SymMap and the Encyclopedia of Traditional Chinese Medicine (ETCM), and disease targets were retrieved by DisGeNET and GeneCards databases. The intersections of compound targets and disease targets were used to obtain the predicted targets of song-decoction on ASCVD. The Protein-Protein Interaction (PPI) network diagram was constructed through STRING database, and key compounds and targets of Shengmaiyin (Dangshen prescription) acting on ASCVD were obtained through Cytoscape. Finally, the enriched key targets were put for Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis through the Database for Annotation,Visualization and Integrated Discovery(DAVID). Result:There were 33 key compounds and 25 key targets of Shengmaiyin (Dangshen prescription) for ASCVD. The GO analysis showed that the biological functions of Shengmaiyin (Dangshen prescription) in the treatment of key ASCVD targets mainly involved biological processes, such as the regulation of apoptosis, inflammatory response, regulation of nitric oxide synthesis and regulation of insulin secretion. The KEGG pathway was mainly enriched in 20 signaling pathways, including tumor necrosis factor(TNF) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, apoptosis signaling pathway and estrogen signaling pathway. Conclusion:Through network pharmacology, this study explored active ingredients and potential targets of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD at the molecular level, preliminarily verified the mechanism of action of Shengmaiyin (Dangshen prescription), and laid a theoretical foundation for further study on the mechanism of action.
RESUMEN
Objective:To study the protective effect and mechanism of artemisinin on systemic inflammatory response syndrome (SIRS)mice using endotoxin (LPS)-induced SIRS mouse model. Method:Male BALB/c mice aged 5-7 weeks were randomly divided into normal group, LPS model group, low, medium and high-dose artemisinin groups (25, 50, 100 mg·kg-1) and ibuprofen group (39 mg·kg-1). LPS (10 mg·kg-1) was intraperitoneally injected at the 7th day after the prophylaxis. According to the SIRS clinical diagnostic criteria, the respiratory rate, rectal temperature, lung index, spleen index, glycolipid metabolism, brain tissue inflammatory factors, and phosphorylation of lung tissue inflammation-related proteins were measured. Result:Intraperitoneal injection of LPS significantly reduced the respiratory rate of mice (P<0.05), body temperature decreased significantly (P<0.01), spleen index increased significantly (P<0.01), peripheral blood neutrophil percentage increased significantly (P<0.05), percentage of monocytes decreased significantly (P<0.01), thrombocyte decreased (P<0.01), platelet specific ratio decreased (P<0.01), total cholesterol content in plasma decreased (P<0.01), plasma glucose content decreased (P<0.01). The expression of interleukin-1β increased in hippocampus and cortex of brain tissue (P<0.01), and the secretion of tumor necrosis factor-α increased in hippocampus and cortex of brain tissue (P<0.01). The expression of phosphorylated protein STAT1 was increased (P<0.01), and the expression of phosphorylated protein c-Jun was increased (P<0.01). After the administration of artemisinin, the body temperature and the respiratory rate of mice induced by LPS were significantly increased, the pathological changes of various organs induced by LPS were alleviated, the hypoglycemia induced by LPS was significantly increased (P<0.05), the levels of inflammatory factors in hippocampus and cortex was significantly reduced, and the expressions of phosphorylated proteins STAT1 and c-Jun in lung tissue were significantly reduced (P<0.05, P<0.01). Conclusion:Artemisinin has a significantly protective effect on SIRS mice induced by intraperitoneal injection of LPS possibly by reducing the secretion of inflammatory factors TNF-α and IL-1β.
RESUMEN
BACKGROUND@#The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.@*METHODS@#All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.@*RESULTS@#At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.@*CONCLUSIONS@#Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.@*TRIAL REGISTRATION@#ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132.
RESUMEN
The aim of this paper was to obtain low toxicity and high efficiency anti-tumor Chinese medicine through screening the combination ratios of Momordicae Semen and Epimedii Folium, and to explore the anti-tumor mechanism of the combination of two drugs by observing their effect on apoptosis-related proteins in cancer cells. Methyl thiazolyl tetrazolium(MTT) assay was used to observe the effect of drug combination on the proliferation of tumor cells from different tissue sources. The effects of the combination of the two drugs on tumor cells were analyzed by Compusyn software. Plate cloning assay was used to observe the effect of combination of these two drugs on the proliferation of A549 cells in vitro. The expression of reactive oxygen species(ROS) and apoptotic proteins p53, Bcl-2 and Bax were compared by using ROS kit and Western blot. Lewis lung cancer model was used to observe the anti-tumor effect of drugs in vivo. The results showed that the anti-tumor effect of their ethanol extract was more significant than that of water extract, and the anti-proliferation effect was strongest when the ratio was 1∶1(P<0.05). Compusyn analysis showed that the combination of the two drugs had synergistic effect. Further studies showed that after combined use, the number of clonogen formation in A549 cells was significantly reduced(P<0.01); ROS production was increased; the expression of apoptosis-related protein p53 was up-regulated, and the ratio of Bcl-2/Bax was decreased. In vivo animal study showed that the tumor inhibition rate was 53.06%(P<0.05) in the high dose group. As compared with the single use of the two drugs, the combination of the two drugs had more significant anti-proliferative effect on tumors, and the optimum ratio was 1∶1. The combination of the two drugs at a ratio of 1∶1 inhibited the proliferation of various tumor cells, and had no significant effect on normal liver cells LO2 when compared with other ratios. Therefore, it can be preliminarily inferred that the combination of the two drugs may have the effect of synergism and detoxification. Further studies showed that the combination of the two drugs can significantly inhibit the proliferation of A549 cells, and its mechanism may be related to the activation of endogenous apoptotic pathway. In vivo experiments also showed that the tumor inhibition rate increased with the increase of drug concentration.
Asunto(s)
Animales , Humanos , Células A549 , Antineoplásicos Fitogénicos/farmacología , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Medicamentos Herbarios Chinos/farmacología , Epimedium/química , Neoplasias Pulmonares/tratamiento farmacológico , Momordica/química , Neoplasias Experimentales/tratamiento farmacológico , Hojas de la Planta/químicaRESUMEN
Objective: To investigate the protective effect of phenolic compounds 4-hydroxybenzylideneacetone and (HBAc)3,4-dihydroxybenzylideneacetone (DHBAc) of Osmundae Rhizoma on the systemic inflammatory response syndrome (SIRS) in mice by establishing the mice model of SIRS.Method: BALB/c mice were randomly divided into the normal group,the SIRS model group and the different doses of HBAC and DHBAc group (25,50,100 μg·kg-3).Lipopolysaccharides (LPS) was injected intraperitoneally after 7 days of prophylactic administration.After 5 hours of modeling,the anus temperature,respiratory rate,the number of white blood cell (WBC) and platelets (PLT),WBC classification,glycolipid metabolism,inflammatory factor and signal transducing phosphorylated protein of lung were measured.Result: Intraperitoneal injection with LPS (6 mg·kg-1) in mice can significantly reduce the respiratory rate (PPPPPβ(PPPPPPPPPβ(PConclusion: The SIRS model can be established through intraperitoneal injection of LPS.HBAc and DHBAc have protective effects on endotoxin-induced SIRS in mice,and may exert anti-inflammatory effects through IκB and c-JUN pathways.
RESUMEN
In the background of the high incidence and high mortality of cardiovascular diseases,atherosclerosis is the main pathological feature of cardiovascular diseases and the core pathological basis for disease progression. In the evolution of atherosclerotic plaques,the rupture of unstable plaques,plaque shedding and formation of thrombosis are the most dangerous parts. In this process,the formation of plaque fibrosis is the core mechanism regulating plaque stability. Additionally,fibrosis reflects dynamic changes in the inflammatory processes and pathological changes. In view of the inflammation regulation and fibrosis regulation,this paper clarified the process of atherosclerotic plaque,explained the roles of relevant inflammatory cells and cytokines in plaque stability,and summed up drug researches related with stable plaque in recent years. In the future,improving the fibrosis will be a new idea for stabilizing plaque in atherosclerosis drug development.