#VACINAPARATODOS: sentidos atribuídos por brasileiros à primeira dose da imunização contra a covid-19 no Instagram / #VACINAPARATODOS: meanings attributed by Brazilians to the first dose of immunization against covid-19 on Instagram / #VACINAPARATODOS: significados atribuidos por brasileños a la primera dosis de inmunización contra covid-19 en InstagramAutor

Este artigo se baseia em uma pesquisa que teve como objetivoapreender os sentidos atribuídos por brasileiros à primeira dose da imunização contra a covid-19. Trata-se de uma análise netnográfica. Os dados foram coletados em 2021 por meio da hashtag VACINAPARATODOS no Instagram. Os métodos utilizados para análise de dados foram: análise de similitude, com auxílio do software IRAMUTEQ e da análise do Discourse of the collective subject (discurso do sujeito coletivo), de Lefevre. Os resultados apontaram como ideias centrais: a emoção positiva e o sentimento de gratidão; a emoção negativa e o sentimento atribuído às vidas perdidas e ao negacionismo; o significado da primeira dose e o sentimento de esperança; a imunização e o exercício da cidadania: ato de consciência, responsabilidade e respeito. Os sentidos atrelados à oportunidade de acesso à vacina mostraram a dualidade de sentimentos que vão desde sensações positivas de reconhecimento e valorização até sentimentos negativos, de revolta e indignação, diante da hesitação vacinal e dos discursos antivacina.

This article bases on a research that aimed to understand the meanings attributed by Brazilians to the first dose of immunization against covid-19. A netnographic analysis was carried out. The data was collected in 2021 using the hashtag VACINAPARATODOS on Instagram. The methods used analyse the data were: similarity analysis, with the aid of the IRAMUTEQ software and of the analysis of Discourse of the collective subject, developed by Lefevre. The results pointed out the following central ideas: positive emotion and a feeling of gratitude; the negative emotion and a feeling attributed to lost lives and to denialism; the meaning of the first dose and the feeling of hope; the immunization and the exercise of citizenship: an act of conscience, responsibility and respect. The meanings linked to the opportunity to access the vaccine showed a duality of feelings ranging from positive feelings of recognition and appreciation to negative feelings of revolt and indignation, in the face of vaccine hesitancy and of the anti-vaccine discourses.

Este artículo se basa en una investigación que tuvo como objetivo comprender los significados atribuidos por los brasileños a la primera dosis de inmunización contra la covid-19. Se realizó un análisis netnográfico. Los datos fueron recogidos en 2021 a través del hashtag VACINAPARATODOS en Instagram. Los métodos utilizados para el análisis de los datos fueron: análisis de similitud, con ayuda del softwareIRAMUTEQ y del análisis del Discourse of collective subject (Discurso del sujeto colectivo), de Lefevre. Los resultados evidenciaron como ideas centrales: la emoción positiva y el sentimiento de gratitud; la emoción negativa y el sentimiento atribuido a las vidas perdidas y al negacionismo; el significado de la primera dosis y el sentimiento de esperanza; la inmunización y el ejercicio de la ciudadanía: un acto de conciencia, responsabilidad y respeto. Los significados vinculados a la oportunidad de acceder a la vacuna mostraron la dualidad de sentimientos que van desde sentimientos positivos de reconocimiento y aprecio hasta sentimientos negativos de revuelta y indignación, frente a las dudas sobre las vacunas y los discursos antivacunas.

Network meta-analysis of pembrolizumab as monotherapy and in combination with chemotherapy for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma / Metanálise em rede comparativa de pembrolizumabe como monoterapia e em combinação com quimioterapia para tratamento de primeira linha de carcinoma de células escamosas da cabeça e pescoço recorrente ou metastático

Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.

Pembrolizumabe em monoterapia ou em combinação com quimioterapia é aprovado como tratamento de primeira linha em carcinoma de células escamosas recorrente/metastático de cabeça e pescoço (CECCP R/M) com base na melhora da sobrevida global (OS), em comparação com o esquema EXTREME no estudo KEYNOTE-048. Esse estudo comparou os resultados clínicos de pembrolizumabe com outros tratamentos recomendados de primeira linha em CECCP R/M por meio de uma metanálise de rede bayesiana. Uma revisão sistemática da literatura foi conduzida em julho de 2022, a partir da qual seis ensaios clínicos que atendiam aos critérios de elegibilidade de pacientes do KEYNOTE-048 foram incluídos na rede. Os desfechos de OS e sobrevida livre de progressão (PFS) foram comparados na indicação de pembrolizumabe (população total para pembrolizumabe em combinação com quimioterapia e população com escore positivo combinado [CPS] ≥ 1 em monoterapia com pembrolizumabe). Foi observada melhora significativa na OS para pembrolizumabe em combinação com quimioterapia e monoterapia com pembrolizumabe versus o esquema EXTREME (razão de risco, intervalo de confiança de 95%: 0,72, 0,60-0,86; 0,73, 0,60-0,88), platina+5-FU (0,58, 0,43-0,76; 0,58, 0,44-0,78) e platina+paclitaxel (0,53, 0,35-0,79; 0,53, 0,35-0,81), respectivamente. Uma tendência numérica não significativa de melhoria na OS foi observada em relação ao esquema TPEx. A PFS foi comparável com a maioria dos tratamentos de primeira linha e melhor em relação à platina+5-FU (0,48, 0,36-0,64; 0,59, 0,45-0,79). Análises adicionais em subgrupos com CPS mais elevado também mostraram resultados consistentes. No geral, os resultados de nosso estudo mostraram melhora nos desfechos de OS em comparação aos tratamentos de primeira linha alternativos, consistentes com os achados do estudo KEYNOTE-048. Esses dados apoiam o uso de pembrolizumabe como opção de tratamento em primeira linha em pacientes com CECCP R/M.

Automatic detection and classification of disease in citrus fruit and leaves using a customized CNN based model / Detección y clasificación automática de enfermedades en frutas y hojas de cítricos utilizando un modelo basado en CNN personalizado

India's commercial advancement and development depend heavily on agriculture. A common fruit grown in tropical settings is citrus. A professional judgment is required while analyzing an illness because different diseases have slight variati ons in their symptoms. In order to recognize and classify diseases in citrus fruits and leaves, a customized CNN - based approach that links CNN with LSTM was developed in this research. By using a CNN - based method, it is possible to automatically differenti ate from healthier fruits and leaves and those that have diseases such fruit blight, fruit greening, fruit scab, and melanoses. In terms of performance, the proposed approach achieves 96% accuracy, 98% sensitivity, 96% Recall, and an F1 - score of 92% for ci trus fruit and leave identification and classification and the proposed method was compared with KNN, SVM, and CNN and concluded that the proposed CNN - based model is more accurate and effective at identifying illnesses in citrus fruits and leaves.

El avance y desarrollo comercial de India dependen en gran medida de la agricultura. Un tipo de fruta comunmente cultivada en en tornos tropicales es el cítrico. Se requiere un juicio profesional al analizar una enfermedad porque diferentes enfermedades tienen ligeras variaciones en sus síntomas. Para reconocer y clasificar enfermedades en frutas y hojas de cítricos, se desarrolló e n esta investigación un enfoque personalizado basado en CNN que vincula CNN con LSTM. Al utilizar un método basado en CNN, es posible diferenciar automáticamente entre frutas y hojas más saludables y aquellas que tienen enfermedades como la plaga de frutas , el verdor de frutas, la sarna de frutas y las melanosis. En términos de desempeño, el enfoque propuesto alcanza una precisión del 96%, una sensibilidad del 98%, una recuperación del 96% y una puntuación F1 del 92% para la identificación y clasificación d e frutas y hojas de cítricos, y el método propuesto se comparó con KNN, SVM y CNN y se concluyó que el modelo basado en CNN propuesto es más preciso y efectivo para identificar enfermedades en frutas y hojas de cítricos.

Anti-COVID-19 mechanism of Anoectochilus roxburghii liquid based on network pharmacology and molecular docking / 药学学报

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Mechanism of Sanhuang Xiexintang in Protecting Stress Gastric Ulcer in Rats / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Analysis and verification of the effect of Yi Qi Yang Yin decoction on rheumatoid arthritis / 中国临床药理学与治疗学

AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF - κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4 / PPARγ/NF - κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.

Mechanism of Yi-xin-yin oral liquid according to homotherapy for heteropathy theory based on UHPLC-Q-TOF/MS combined with network pharmacology and molecular docking techniques / 中国临床药理学与治疗学

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

UPLC-QE-MS combined network pharmacological analysis of the mechanism of ulcerative colitis / 中国临床药理学与治疗学

AIM:To explore the anti-ulcerative colitis mechanism of Buzhongyiqi pills based on the network pharmacology and experimental verification. METHODS: UPLC-QE-MS was used for qualitative analysis of Buzhongyiqi pills. Targets of the chemistry constituents and the disease were retrieved from GeneCards. Then the protein-protein interaction (PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Ulcerative colitis mouse model was established to verify the key targets. RESULTS: A total of 41 constituents migrating of Buzhongyiqi pills were identified. A total of 123 common targets of the constituents and the disease and 24 core targets were screened out.KEGG enrichment and PPI network analysis showed that Buzhongyiqi pills may play a role in the treatment of ulcerative colitis through Akt, PI3K and other pathways. Furthermore, the results of animal experiments showed that Buzhongyiqi pills could significantly improve the depression behaviors of ulcerative colitis, reduce the levels of IL-6 and TNF-α in serum, inhibition Akt/PI3K signaling, and reduce the protein expression of PI3K. CONCLUSION: Buzhongyiqi pills may play a role in the treatment of ulcerative colitis by inhibition Akt / PI3K signaling pathway, and inhibiting PI3K and reduce the levels of IL-6 and TNF-α in the mice.

Effects of Tao Hong Si Wu decoction on IncRNA expression in rats with occlusion of middle cerebral artery / 中国药理学通报

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Mechanism of Ruanmai decoction in treating atherosclerosis based on YWHAZ/p38MAPK/CASP3 signaling pathway / 中国药理学通报

Aim To explore the mechanism of action of Ruanmai decoction in treating atherosclerosis through network pharmacology. Methods The chemical components and targets of Ruanmai decoction were queried using TCMSP. Relevant targets for atherosclerosis were retrieved from DrugBank, GeneCards, OMIM, and TTD databases. The " Drug-Active Ingredient-Target" PPI network was constructed using Cyto-scape software. GO and KEGG enrichment analysis were performed using the David database. Molecular docking verification of key components with core targets was conducted using the Seesar software. Atherosclerosis mouse models were established by feeding ApoE mice with a high-fat diet, and Ruanmai decoction granules were administered orally. Aortic pathological sections were stained, blood lipids were measured, and immunofluorescence was used to detect Mac2 and YWHAZ protein expression. Western blot was used to detect p-p38MAPK and C-CASP3 protein expression. Results Ruanmai decoction screened a total of 72 active drug components corresponding to 168 target genes for the treatment of atherosclerosis. The targets were primarily enriched in biological processes related to lip-id metabolism, inflammation and immunity, oxidative stress, vascular endothelial function, cell proliferation and apoptosis, glycolysis, and ubiquitination. Signaling pathways such as МАРК, TNF, PDK-Akt, and IL-17 were also involved. Animal experiments verified that RMJ could regulate the p38MAPK signaling pathway by down-regulating key targets YWHAZ, p-p38MAPK, and C-CASP3, thereby reducing AS inflammation and inflammation-induced apoptosis. Conclusions Ruanmai decoction can inhibit the expression of YWHAZ and activate the p38MAPK signaling pathway, potentially improving vascular inflammation, lipid metabolism, oxidative stress, and other pathological processes by regulating the МАРК, TNF, PDK-Akt, and IL-17 signaling pathways, thus preventing and treating atherosclerosis.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification / 中国药理学通报

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL

Study on relationship of target organ injury of mechanism and "structure-effect-dose" of Hedysari Radix during radiotherapy-chemotherapy induced / 中国药理学通报

Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "

Mechanism of Fufang Congrong Yizhi Capsules in treatment of mild cognitive impairment based on network pharmacology / 中国药理学通报

Aim To predict the mechanism of Fufang Congrong Yizhi Capsules (FCYC) in the treatment of mild cognitive impairment (MCI) by network pharmacology method, and further validate it in combination with cellular experiments. Methods TCMSP, Gene-Cards, OMIM and TTD databases, Chinese Pharmacopoeia and related literature were used to screen the active ingredients of FCYC and the targets of MCI treatment. The TCM-compound-target-disease network and PPI of intersection targets were constructed, and the GO and KEGG analysis were performed by the Ehamb bioinformation platform. GO and KEGG analysis were performed through Yihanbo biological information platform. Cell model of MCI was established by PC-12 injury induced by Aβ

Exploration of molecular mechanism of Selaginella moelledorffii Hieron. in treatment of laryngeal cancer based on network-based pharmacology, molecular docking techniques and experimental validation / 中国药理学通报

Aim To explore the molecular mechanism of Selaginella moelledorffii Hieron. in the treatment of laryngeal cancer. Methods According to the relevant literature reports, the chemical constituents of S. moellendorffii were obtained, and the active ingredients were screened out through the SwissADME database, and the targets were screened through the PharmMapper database. The laryngeal cancer-related targets were collected by searching OMIM and other databases, and the Venny 2.1.0 online platform was used to obtain the intersection of the two. Protein interaction analysis of the potential targets was performed using the STRNG platform. GO functional analysis and KEGG pathway analysis was carried out using DAVID database. Visual networks were built with Cytoscape 3.8.0 software. Molecular docking was validated by SYBYL-X 2. 0 software. MTT method, Hoechst 33258 staining method and Western blotting were also used for validation. Results At the molecular level, a total of 110 active ingredients of S. moellendorffii and 82 drug targets were screened out, 1,608 targets related to laryngeal cancer, and intersection of 34 targets. GO analysis yielded 135 entries, and KEGG analysis yielded a total of 61 pathways. Molecular docking results showed that the 11 key active ingredients such as 2", 3"-dihydrooch-naflavone wood flavonoids and 4 core target proteins such as MAPK1 had 95. 5% of good docking activity. At the cellular level, SM-BFRE was screened for its strongest inhibitory effect on laryngeal cancer cell proliferation through MTT assay. Furthermore, Hoechst 33258 staining showed that the decrease in Hep-2 cell viability produced by SM-BFRE was related to cell apoptosis. Finally, Western blot verified that SM-BFRE inhibited PI3K/Akt/NF through inhibition- K B/COX-2 pathway to induce apoptosis in laryngeal cancer cells. Conclusions To sum up, it fully reflects the multicomponent, multi-target, and multi-channel synergistic effect of S. moellendorffii in the treatment of laryngeal cancer, and provides a theoretical reference for further elucidation of the mechanism of action of S. moellendorffii in the treatment of laryngeal cancer.

Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Analysis of effective components of Agaricus blazei Murill extract by LC-MS and network pharmacology analysis in treatment of chronic myeloid leukemia / 中国药理学通报

Aim To explore the potential targets and related signaling pathways of Agaricus blazei Murill (AbM ) extract in the treatment of chronic myeloid leukemia (CML) based on liquid chromatography mass spectrometry ( LC-MS ), network pharmacology, molecular docking, and were further verified by experiments in vitro. Methods The active components of AbM extract were retrieved from LC-MS, Swiss Target Prediction database was used to predict related targets, and CML disease target genes were obtained from Gen- eCards and DisGeNET databases. After screening the common targets of drug and CML, the protein-protein interaction network of the common targets was performed by STRING, and GO and KEGG enrichment a- nalysis were done by DAVID database. Cytoscape software was used to construct the network of target protein. Molecular docking was carried out by DockThor, and the Pymol software was used to make a visual picture. The inhibitory effect of AbM extract on leukemia cells K562 was determined by CCK-8 experiment, and the effect of AbM extract on the expression and phosphorylation level of related proteins was verified by Western blot. Results The prediction results showed that 126 active components of AbM extract, and 172 common targets were collected. KEGG pathway analysis results showed that PI3K/Akt/mTOR signaling pathway might play an important role in the treatment of CML disease. The IC

A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer / 中国药理学通报

Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

Mechanism of Wen Shen Xuan Bi Tang in treatment of osteoporosis based on network pharmacology and animal experimental verification / 中国药理学通报

Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.

Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking / 中国药理学通报

Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I