Active Target Research Articles

Insights into the mechanism of Danggui Liuhuang Tang in treating night sweats: A network pharmacology and molecular docking approach.

Night sweats can occur independently or in association with a number of medical conditions and can significantly disrupt daily life. This study focuses on the treatment of primary night sweats. Despite the considerable interest in Danggui Liuhuang Tang (DGLHT), an effective traditional Chinese medicine formula, its mechanism of action remains unknown. There is also no existing literature on the subject. Network pharmacology and molecular docking techniques. Network pharmacology techniques were employed to identify 109 active ingredients and 808 potential targets of DGLHT, as well as 2385 targets associated with night sweating diseases. The screening process yielded 375 common targets shared between DGLHT and night sweating. These included the active ingredients baicalein, quercetin, huarangiin, and tetrahydroafrican antipyrine, and the core targets interleukin 6, serine/threonine protein kinase 1, tumor necrosis factor, GAPDH enzyme, and Src protein kinase were identified. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that DGLHT exerts its therapeutic effects primarily by modulating the PI3K-Akt signaling pathway, neuroactive ligand-receptor interactions, lipid metabolism, and atherosclerosis pathways. Molecular docking revealed strong binding activity between the main active ingredients and their potential targets. The research identifies promising active ingredients and targets related to the effectiveness of DGLHT in controlling night sweats, thus contributing to the further exploration of potential therapeutics for this condition. In addition, the results of this experiment provide a basis for future research into night sweats.

Exploring the Mechanism of Modified Zexie Decoction Against Metabolic Associated Fatty Liver Disease Based on Network Pharmacology and Experimental Validation.

The incidence of metabolic-associated fatty liver disease (MAFLD) increases annually. Modified Zexie Decoction (MZXD) can treat this disease; however, their mechanisms of action are uncertain. This study evaluated the mechanisms of MZXD against MAFLD based on network pharmacology, molecular docking, and in vivo experiments. The main active compounds, targets and signaling pathways of MZXD against MAFLD were obtained using network pharmacological analysis. Underlying mechanisms were validated by molecular docking and in vivo assays. Forty-one active ingredients and 197 intersection targets were identified. The main active ingredients include quercetin, luteolin, isorhamnetin, 3-methylhexane, and 3β- acetoxyatractylone. The main targets were TP53, JUN, HSP90AA1, MAPK1, MAPK3, AKT1, NF-κB p65, TNF, ESR1, FOS, and IL-6. The pathway enrichment analysis indicated that MZXD was related to the IL-17, TNF, and PI3K-AKT signaling pathways. Molecular docking suggested that these active ingredients bound strongly to TNF, IL-6, and NF-κB p65, which are integral components of the TNF pathway. In the rat MAFLD model, MZXD attenuated high-fat diet( HFD)-induced liver injury and lipid accumulation, decreased the serum levels of the inflammatory mediators TNF-α, IL6, and IL-1β, and inhibited the protein expression of TNF-α, IL6, p- IKB-α and p-NF-κB p65. Furthermore, immunohistochemistry results showed that MZXD attenuated the F4/80 staining intensity of the liver compared with the model group. Collectively, our results suggested that MZXD could improve MAFLD by downregulating TNF/NF-κB signaling mediated macrophage activation.

YOUTH PEOPLE’S CIVIC AND POLITICAL ENGAGEMENT AT SMAN 1 GIRI, BANYUWANGI REGENCY

This community service activity aims to increase the political and civil literacy of novice voters in preparation for the 2024 Simultaneous Elections in Indonesia. The targets of this community service activity are school students or youth who are at least 17 years old in the year the 2024 Simultaneous Election will be held. Youth were chosen as the main target because they are a group with a large proportion in the 2024 election contestation which will determine the future of democracy. As new voters, they need preparation and a deep understanding of how to participate in the political process effectively to determine the direction and policies of government. For this reason, the Public Administration Department of Universitas Airlangga will partner with the East Java Provincial Education Office which will later provide guidance to the SMAN 1 Giri, Banyuwangi Regency to hold a community service program at the school. Community service activities will involve understanding the political system, democratic processes, political issues, and the importance of active political participation. Activities will be carried out through three main stages: preparation, implementation and evaluation. The preparatory stage involves collecting and compiling relevant political and civic literacy materials. Next, the implementation stage will involve counseling, workshops and group discussions to provide in-depth understanding to novice voters. The evaluation stage will be carried out to measure the effectiveness of the program and obtain feedback from participants. It is hoped that this activity will provide a fundamental contribution in increasing the political and civil literacy of novice voters. With a better understanding of the political system, first-time voters will be able to make good political decisions, participate actively in the political process, and critically evaluate the information they receive.

Analysis of gut microbiota-derived metabolites regulating pituitary neuroendocrine tumors through network pharmacology.

Pituitary neuroendocrine tumors (PitNETs) are a special class of tumors of the central nervous system that are closely related to metabolism, endocrine functions, and immunity. In this study, network pharmacology was used to explore the metabolites and pharmacological mechanisms of PitNET regulation by gut microbiota. The metabolites of the gut microbiota were obtained from the gutMGene database, and the targets related to the metabolites and PitNETs were determined using public databases. A total of 208 metabolites were mined from the gutMGene database; 1,192 metabolite targets were screened from the similarity ensemble approach database; and 2,303 PitNET-related targets were screened from the GeneCards database. From these, 392 overlapping targets were screened between the metabolite and PitNET-related targets, and the intersection between these overlapping and gutMGene database targets (223 targets) were obtained as the core targets (43 targets). Using the protein-protein interaction (PPI) network analysis, Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway and metabolic pathway analysis, CXCL8 was obtained as a hub target, tryptophan metabolism was found to be a key metabolic pathway, and IL-17 signaling was screened as the key KEGG signaling pathway. In addition, molecular docking analysis of the active metabolites and target were performed, and the results showed that baicalin, baicalein, and compound K had good binding activities with CXCL8. We also describe the potential mechanisms for treating PitNETs using the information on the microbiota (Bifidobacterium adolescentis), signaling pathway (IL-17), target (CXCL8), and metabolites (baicalin, baicalein, and compound K); we expect that these will provide a scientific basis for further study.

Network Pharmacology Analysis and Retrospective Cohort Study Revealing the Effect of Qingyi Decoction on Intestinal Paralysis in Patients with Severe Acute Pancreatitis.

Intestinal dysfunction plays an important role in the clinical progress and prognosis of severe acute pancreatitis (SAP). Qingyi decoction (QYD) has shown beneficial effects on intestinal function recovery, but the prevention actions of the QYD on intestinal paralysis and its mechanism have not been fully explored. The possible molecular mechanism was unraveled by network pharmacology, including active ingredients and potential target prediction, as well as GO, KEGG, and REATCOME pathway enrichment analyses. The potential interactions between the main active ingredients of the QYD and core genes were explored by molecular docking. A retrospective cohort study on 137 patients with SAP from Tianjin Nankai Hospital was conducted to evaluate the preventive effect of QYD on intestinal paralysis. A total of 110 active ingredients in QYD were screened out, and 37 key targets were predicted by network pharmacology. GO, KEGG, and REATCOME enrichment analyses showed that bioinformatics annotation of the hub genes was mainly involved in intestinal epithelial functions and inflammatory response pathways. The main components of QYD possessed good affinity with IL-6, TNF, CASP3, CXCL8, and CRP by molecular docking. Patients who used QYD plus usual care seemed to have fewer intestinal paralysis rates, lower risk of renal insufficiency, ARDS and blood purification therapy, and shorter hospital and ICU stays. The multivariable regression analyses indicated that the mode of nasogastric and enemas administration of QYD (P = 0.010) and timely intervention with QYD (P = 0.045) were the independent protective factors for intestinal paralysis prevention in patients with SAP. In conclusion, QYD can be used as an effective adjuvant procedure to prevent the occurrence and development of intestinal paralysis in patients with SAP. The mechanisms may be involved in the anti-inflammatory response and maintenance of intestinal epithelial function.

Investigation of the Lipid-Lowering Activity and Mechanism of Three Extracts from Astragalus membranaceus, Hippophae rhamnoides L., and Taraxacum mongolicum Hand. Mazz Based on Network Pharmacology and In Vitro and In Vivo Experiments.

Hyperlipidemia is a metabolic disorder characterized by abnormal lipid metabolism, resulting in lipid accumulation in the plasma. According to reports, medicinal and edible plants can reduce the risk of metabolic diseases such as hyperlipidemia. This study investigates the effects and mechanisms of Astragalus membranaceus extract (AME), Hippophae rhamnoides L. extract (HRE), and Taraxacum mongolicum Hand. Mazz extract (TME) on hyperlipidemia. Active compounds and potential gene targets of AME, HRE, and TME were screened using LC-MS and TCMSP databases, and hyperlipidemia targets were detected from the OMIM and DisGeNet databases. A drug-target pathway disease network was constructed through protein interactions, GO enrichment, and KEGG pathway analysis. Finally, the lipid-lowering effects of three extracts were validated through in vitro HepG2 cell and in vivo animal experiments. The results show that LC-MS and network pharmacology methodologies identified 41 compounds and 140 targets. KEGG analysis indicated that the PI3K-Akt and MAPK signaling pathways significantly treat hyperlipidemia with AHT. In vitro experiments have shown that AHT is composed of a ratio of AME:HRE:TME = 3:1:2. HepG2 cell and animal experiments revealed that AHT exhibits strong lipid-lowering and antioxidant properties, significantly regulating the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). It is worth noting that AHT can effectively downregulate the protein expression levels of p-AKT/AKT and p-PI3K/PI3K and upregulate the protein expression levels of p-AMPK/AMPK and SIRT1, verifying the results predicted by network pharmacology. This study presents a novel approach to utilizing these natural plant extracts as safe and effective treatments for hyperlipidemia.

Exploration of Active Ingredients, Targets, and Potential Mechanisms of Er-Miao-San in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology

Background Er-Miao-San (EMS) is a classic prescription in Traditional Chinese Medicine (TCM) for the treatment of colorectal cancer (CRC) and has shown promising therapeutic effects in clinical practice. However, the specific components and molecular mechanisms of EMS remain unclear. Purpose The aim of this study was to analyze the effective components and molecular mechanisms of EMS in treating CRC through network pharmacology techniques and experimental validation. Materials and Methods The Traditional Chinese Medicine Systems Pharmacology database was used to screen the main active chemical components and targets of the EMS formula. The compound structures were verified using the PubChem database, which is an organic small-molecule bioactivity database. GeneCards and OMIM databases were utilized to predict target genes related to CRC. The Cytoscape 3.8 software was used to construct a “Drug-Active Ingredient-Target-Disease” intersection network. The STRING database was employed to analyze the core target protein–protein interaction network shared by EMS and CRC. The core targets were further subjected to Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the R language. Molecular docking between the core targets and the major active chemical components of EMS was performed using AutoDock software. The impact of the core targets on the prognosis of CRC patients was analyzed using the R language. Subsequently, we validated the potential mechanisms predicted by network pharmacology for the inhibition of CRC cell proliferation by the key proteins in the relevant pathways through CCK8 cell proliferation assays and Western blot experiments. Results Molecular docking results showed good docking affinity between the key active components, such as quercetin and baicalein, of EMS and the core targets. Kaplan–Meier survival analysis demonstrated a close correlation between the core targets and the survival prognosis of CRC patients. Cellular experiments showed that EMS significantly inhibited the proliferation of CRC cells and may promote apoptosis and autophagy of CRC cells by suppressing the expression of key proteins in the PI3K/AKT pathway. Conclusion The TCM formula EMS exerts anti-CRC effects through multiple pathways and targets, improving the prognosis and extending the survival period of CRC patients. This study provides preliminary insights into the effective components and molecular mechanisms of EMS in the treatment of CRC, which were preliminarily validated through molecular docking and experimental approaches.

Implementation of Physical Activity in the Curricula of Medical Schools and Healthcare Professions Across Europe: The VANGUARD Project Study Protocol.

The 2018 published World Health Organisation (WHO) Europe physical activity factsheet reports, specify agreed targets for physical activity and articulate the need to improve the education of medical doctors and healthcare practitioners in order to increase physical activity and reduce sedentary time in people at risk and/or living with Noncommunicable Diseases (NCDs). Given the dearth of relevant initiatives and the continuous need to increase physical activity participation towards better health management of NCDs, the aim of this study is to embed physical activity in the undergraduate curricula of future frontline healthcare professionals (medical doctors and allied health professions) in European countries. The Virtual Advice, Nurturing, Guidance on Universal Action, Research and Development for physical activity and sport engagement (VANGUARD) project consists of a collaborative partnership Consortium between six European Universities, WHO Europe and Ministry representatives that has been developed to implement physical activity in the curricula of medical schools and healthcare professions. The methodology of the VANGUARD project is informed by the WHO implementation guidance and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. Through a carefully planned implementation process and via using established appropriate implementation evaluation tools, the end result of the VANGUARD project will be the a) implementation of a physical activity module in six different European Universities (five medical schools and one physiotherapy department) and b) development of a toolkit/guide, in order to assist other healthcare systems and European Universities to develop relevant grass-root innovations for addressing the decline in physical activity levels.

Investigation of the pharmacological mechanisms of Shenfu injection in acute pancreatitis through network pharmacology and experimental validation

BackgroundShenfu Injection (SFI) has emerged as a prevalent therapeutic intervention in clinical practice for the management of acute pancreatitis (AP). The purpose of this research was to investigate and validate the potential mechanisms of SFI in the treatment of AP through network pharmacology. MethodsNetwork pharmacology was adopted to investigate the potential targets and mechanisms of SFI in the treatment of AP. Molecular docking was employed to evaluate the binding affinity between active components and targets. Single-cell transcriptome analysis was conducted to explore the cell types associated with SFI treatment in AP. In vitro and in vivo models of AP were induced by caerulein. The histopathological changes were observed by HE staining. Cell apoptosis was detected using flow cytometry and Tunel staining. Cell viability was assessed using CCK-8 assay. Western blot and ELISA were used to detect the protein expression and inflammatory cytokines, respectively. ResultsA total of 104 SFI active components were obtained, of which 29 targeted 76 genes. After intersecting with 3370 AP-related genes, 42 SFI treatment AP potential targets were identified. Enrichment analysis revealed that these targets were associated with cell apoptosis, necroptosis, and multiple signal transduction pathways, such as p53, IL-17 and TNF signal pathways, etc. Molecular docking demonstrated that the active components of SFI had good binding affinity with the corresponding targets and the binding ability of NGF and aromadendrene was the strongest. Bioinformatics analysis revealed that SFI treatment in AP is associated with various cell types, including acinar cells, endothelial cells, T cells, dendritic cells, ductal cells, and mesenchymal cells. Furthermore, in vitro experiments demonstrated that SFI induces acinar cell apoptosis in a dose-dependent manner, accompanied by increased expression of cleaved-caspase3/caspase3 and cleaved-caspase8/caspase8 proteins, and inhibition of inflammatory cytokine (TNF-ɑ, IL-1β, and PTGS2) expression. In vivo experiments demonstrated that SFI improved histopathological alterations, reduces inflammation, and promotes apoptosis and the expression of cleaved-casp3 and cleaved-casp8 in AP rats. ConclusionsThis study elucidated the multi-component, multi-target, and multi-cellular characteristics of SFI in the treatment of AP, and confirmed its mechanism of promoting acinar cell apoptosis.

Lycium barbarum Ameliorates Oral Mucositis via HIF and TNF Pathways: A Network Pharmacology Approach.

Oral mucositis is the most common and troublesome complication for cancer patients receiving radiotherapy or chemotherapy. Recent research has shown that Lycium barbarum, an important economic crop widely grown in China, has epithelial protective effects in several other organs. However, it is unknown whether or not Lycium barbarum can exert a beneficial effect on oral mucositis. Network pharmacology has been suggested to be applied in "multi-component-multi-target" functional food studies. The purpose of this study is to evaluate the effect of Lycium barbarum on oral mucositis through network pharmacology, molecular docking and experimental validation. To explore the biological effects and molecular mechanisms of Lycium barbarum in the treatment of oral mucositis through network pharmacology and molecular docking combined with experimental validation. Based on network pharmacology methods, we collected the active components and related targets of Lycium barbarum from public databases, as well as the targets related to oral mucositis. We mapped protein- protein interaction (PPI) networks, performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, and constructed a 'components-disease-targets' network and 'components-pathways-targets' network using Cytoscape to further analyse the intrinsic molecular mechanisms of Lycium barbarum against oral mucositis. The affinity and stability predictions were performed using molecular docking strategies, and experiments were conducted to demonstrate the biological effects and possible mechanisms of Lycium barbarum against oral mucositis. A network was established between 49 components and 61 OM targets. The main active compounds were quercetin, beta-carotene, palmatine, and cyanin. The predicted core targets were IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A and MYC. The enrichment analysis predicted that the therapeutic effect was mainly through the regulation of inflammation, apoptosis, and hypoxia response with the involvement of TNF and HIF pathways. Molecular docking results showed that key components bind well to the core targets. In both chemically and radiation-induced OM models, Lycium barbarum significantly promoted healing and reduced inflammation. The experimental verification showed Lycium barbarum targeted the key genes (IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A, and MYC) through regulating the HIF and TNF signaling pathways, which were validated using the RT-qPCR, immunofluorescence staining and western blotting assays. In conclusion, the present study systematically demonstrated the possible therapeutic effects and mechanisms of Lycium barbarum on oral mucositis through network pharmacology analysis and experimental validation. The results showed that Lycium barbarum could promote healing and reduce the inflammatory response through TNF and HIF signaling pathways.

Bioinformatics analysis based on extracted ingredients combined with network pharmacology, molecular docking and molecular dynamics simulation to explore the mechanism of Jinbei oral liquid in the therapy of idiopathic pulmonary fibrosis

ObjectiveJinbei oral liquid (JBOL), which is derived from a traditional hospital preparation, is frequently utilized to treat idiopathic pulmonary fibrosis (IPF) and has shown efficacy in clinical therapy. However, there are now several obstacles facing the mechanism inquiry, including target proteins, active components, and the binding affinity between crucial compounds and target proteins. To gain additional insight into the mechanisms underlying JBOL in anti-IPF, this study used bioinformation technologies, including network pharmacology, molecular docking, and molecular dynamic simulation, with a substantial amount of data based on realistic constituents. MethodsUsing network pharmacology, we loaded 118 realistic compounds into the SwissTargetPrediction and SwissADME databases and screened the active compounds and target proteins. IPF-related targets were collected from the OMIM, DisGeNET, and GeneCards databases, and the network of IPF-active constituents was built with Cytoscape 3.10.1. The GO and KEGG pathway enrichment analyses were carried out using Metascape, and the protein-protein interaction (PPI) network was constructed to screen the key targets with the STRING database. Finally, the reciprocal affinity between the active molecules and the crucial targets was assessed through the use of molecular docking and molecular dynamics simulation. ResultsA total of 122 targets and 34 tested active compounds were summarized in this investigation. Among these, kaempferol, apigenin, baicalein were present in high degree. PPI networks topological analysis identified eight key target proteins. AGE-RAGE, EGFR, and PI3K-Akt signaling pathways were found to be regulated during the phases of cell senescence, inflammatory response, autophagy, and immunological response in anti-IPF of JBOL. It was verified by molecular docking and molecular dynamics simulation that the combining way and binding energy between active ingredients and selected targets. ConclusionsThis work forecasts the prospective core ingredients, targets, and signal pathways of JBOL in anti-IPF, which has confirmed the multiple targets and pathways of JBOL in anti-IPF and provided the first comprehensive assessment with bioinformatic approaches. With empirical backing and an innovative approach to the molecular mechanism, JBOL is being considered as a potential new medication.

A Network Pharmacological Study on the Treatment of Diminished Ovarian Reserve with Nourishing Yin Formula

Objective To identify the principal constituents of Nourishing Yin Formula, analyze its active substances and effective targets for treating DOR, and explore its potential mechanism of action. Methods The primary active constituents of Nourishing Yin Formula and their putative targets for treating DOR were identified through a search of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (BATMAN-TCM), GeneCards, OMIM, and Uniprot databases. A protein-protein interaction network was constructed using the String database to identify shared targets between the drug and disease. These drug-disease shared targets were then subjected to GO analysis and KEGG pathway enrichment analysis using the DAVID database. Results After screening, the primary chemical constituents of Nourishing Yin Formula for treating DOR were identified, including progesterone, beta-sitosterol, 17-Beta-Estradiol, quercetin, kaempferol, etc Among the 52 critical targets for Nourishing Yin Formula in DOR treatment, the core targets were AKT1, INS, IL6, TNF, EGFR, ESR1, MYC, CTNNB1, NOS3, ERBB2, EDN1, and ESR2. Conclusions The potential mechanism of Nourishing Yin Formula in the treatment of DOR may involve the herbal compound's impact on AKT1, INS, IL6, TNF, and EGFR pathways. It regulates ovarian granulosa cell proliferation and apoptosis, and restores ovarian blood supply.

Exploration of Potential Therapeutic Targets of Shentong Zhuyu Decoction for Ankylosing Spondylitis Based on Network Pharmacology and Molecular Docking.

This study aimed to explore the potential active components and therapeutic targets of Shentong Zhuyu Decoction (SZD) in the treatment of ankylosing spondylitis (AS) through network pharmacology and animal experiments. Targets for AS and related pathways were obtained by network pharmacology, and the pathways with the best binding affinity in molecular docking were verified by animal experiments. The network pharmacology analysis found 248 chemical components, 1068 drug targets and 803 AS-related targets in SZD. After intersection targets analysis, 116 common drug-disease targets were obtained, and matrix metalloproteinase-9, nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) and cytochrome P450 2D6 were identified as the key targets of SZD for the treatment of AS. A total of 2152 biological processes, 38 cellular component expressions and 150 molecular function terms were obtained in gene ontology enrichment analysis, and 153 Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathways were obtained in KEGG enrichment analysis. Molecular docking analysis showed that the absolute binding energies of glypallichalcone and NLRP3, quercetin and NLRP3 and kaempferol and NLRP3 were >7. Animal experiments showed that the expressions of NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 were significantly increased in the model group and the treatment group compared with those in the blank group, and the expression levels in the treatment group were significantly decreased compared with those in the model group (p < 0.05). The active components in SZD, such as baicalin, quercetin, kaempferol and glypallichalcone, may reduce the expression of IL-1β and IL-18 via the NLRP3/Caspase-1 signalling pathway to inhibit the development and progression of inflammation and play a role in the treatment of AS.

A new hybrid gadolinium nanoparticles-loaded polymeric material for neutron detection in rare event searches

Experiments aimed at direct searches for WIMP dark matter require highly effective reduction of backgrounds and control of any residual radioactive contamination. In particular, neutrons interacting with atomic nuclei represent an important class of backgrounds due to the expected similarity of a WIMP-nucleon interaction, so that such experiments often feature a dedicated neutron detector surrounding the active target volume. In the context of the development of DarkSide-20k detector at INFN Gran Sasso National Laboratory (LNGS), several R&D projects were conceived and developed for the creation of a new hybrid material rich in both hydrogen and gadolinium nuclei to be employed as an essential element of the neutron detector. Thanks to its very high cross-section for neutron capture, gadolinium is one of the most widely used elements in neutron detectors, while the hydrogen-rich material is instrumental in efficiently moderating the neutrons. In this paper results from one of the R&Ds are presented. In this effort the new hybrid material was obtained as a poly(methyl methacrylate) (PMMA) matrix, loaded with gadolinium oxide in the form of nanoparticles. We describe its realization, including all phases of design, purification, construction, characterization, and determination of mechanical properties of the new material.

Bio-inspired target detection method of active sonar based on multi-ping perception

Abstract The performance of the active sonar may degrade severely in real ocean environments, influenced by strong reverberation and multiple clutters. Inspired by the observation that dolphins always utilize a train of clicks when detecting underwater, we proposed an active target detection method by making full use of the multi-ping echo information which encompasses the differences between targets and reverberation/clutters. The detection performance of the click trains with different parameters were analysed first to give an insight on signal choice. Then we achieved apparent reverberation/clutter suppression result by utilizing the correlations and differences between multi-ping echoes. Further, the relative motion status between the target and the sonar platform could be perceived within multiple echoes, which strengthened the detection ability of weak target. We proposed two weighting strategies for multi-ping co-utilization. Either equal weights or unequal weights based on the different envelopes of dolphin echolocation click trains were exerted on multiple echoes, which can achieve different perception results for the relative target motion status. Both simulation and lake trials were conducted to verify the performance of the proposed method. The proposed method effectively suppress reveberaton and noise background by around 2-3 dB and achieve bionic detection of weak targets compared to traditional active sonar signal processing method.

Menumbuhkan Kesadaran Orang Tua dalam Deteksi dan Intervensi Stunting Anak Sejak Dini

Stunting is a chronic nutritional problem in children that occurs since in the womb and will have an impact on the child's growth and development in the future. The purpose of this community service activity is to raise public awareness and knowledge in detecting and intervening stunting in children as early as possible. The method used is the delivery of information related to stunting and demonstration of early detection of stunting. The targets of this community service activity are pregnant mothers and mothers who have toddlers in Tembong Village, Carita. The results showed a significant change between before and after participating in the counseling program, namely increasing knowledge and building commitment in mothers to continuously monitor the nutritional status and growth of toddlers at Posyandu.

Exploring the potential mechanisms of Rehmannia glutinosa in treating sepsis based on network pharmacology

The present study utilized network pharmacology to identify therapeutic targets and mechanisms of Rehmannia glutinosa in sepsis treatment. RNA-sequencing was conducted on peripheral blood samples collected from 23 sepsis patients and 10 healthy individuals. Subsequently, the RNA sequence data were analyzed for differential expression. Identification of active components and their putative targets was achieved through the HERB and SwissTarget Prediction databases, respectively. Functional enrichment analysis was performed using GO and KEGG pathways. Additionally, protein-protein interaction networks were constructed and survival analysis of key targets was conducted. Single-cell RNA sequencing provided cellular localization data, while molecular docking explored interactions with central targets. Results indicated significant involvement of identified targets in inflammation and Th17 cell differentiation. Survival analysis linked several targets with mortality rates, while molecular docking highlighted potential interactions between active components and specific targets, such as rehmaionoside a with ADAM17 and rehmapicrogenin with CD81. Molecular dynamics simulations confirmed the stability of these interactions, suggesting Rehmannia glutinosa’s role in modulating immune functions in sepsis.

A comparative study of PEO-PBO content on the targeting and anti-glioma activity of annonaceous acetogenins-loaded nanomicelles

Annonaceous acetogenins (ACGs) have great potential in the treatment of gliomas, but are extremely insoluble and difficult for delivery in vivo. Poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) is an amphiphilic polymer and can reduce the clearance of nanoparticles by mononuclear phagocyte system. To explore an efficient and safe nanomedicine for glioma, ACGs-loaded nanomicelles (ACGs/EB-NCs) was constructed using PEO-PBO as a carrier, and the effect of PEO-PBO content on the targeting and anti-glioma activity were also compared. ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs, the three nanomicellels prepared with different ACGs/EB feeding ratios, had average particle sizes of 148.8±0.5 nm, 32.7±4.1 nm, and 27.1±0.3 nm, respectively. The three ACGs/EB-NCs were spherical in shape, with drug loading content close to the theoretical drug loading content, encapsulation efficiency greater than 97 %, and good stability in physiological media. The cumulative release rates of ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs were 78.2 %, 63.4 %, and 56.3 % within 216 hours, respectively. The inhibitory effects of three ACGs/EB-NCs on U87 MG cells were similar and stronger than free ACGs (P<0.05), with half inhibitory concentration of 0.17, 0.18, and 0.16 ng/mL (P>0.05), respectively. In U87 MG tumor‑bearing mice, ACGs/EB5-NC, ACGs/EB10-NCs and ACGs/EB20-NCs showed a similar tumor inhibition rate of 61.1±5.9 %, 56.2±8.6 % and 64.3±9.4 % (P>0.05), with good safety. Three ACGs/EB-NCs exhibited excellent liver escape ability and tumor targeting ability, with the tumor targeting index greater than 1.5. Three ACGs/EB-NCs were successfully prepared with strong anti-glioma activity and tumor targeting properties, which are expected to provide new options for the clinical treatment of gliomas. The content of PEO-PBO in micelles did not have a significant effect on the tumor targeting and anti-glioma activity of ACGs/EB-NCs.

Exploring the action mechanism of Oxalis corniculata L. decoction in treating osteoarthritis utilizing liquid chromatography-mass spectrometry technology combined with network pharmacology.

This study aimed to identify the chemical constituents of Oxalis corniculata L. decoction. Furthermore, the mechanism of action of O corniculata L. decoction in treating osteoarthritis (OA) was investigated utilizing network pharmacology. The chemical composition of the O corniculata L. decoction was analyzed by employing UHPLC-Q-Exactive-MS/MS. Subsequently, a "compound-target-pathway" network was established through network pharmacology, offering a novel approach to identify the molecular mechanism underlying the treatment of OA with O corniculata L. decoction. Ultimately, the molecular docking technique was employed to validate the binding ability of the active ingredients with therapeutic targets. A total of 539 compounds were identified in O corniculata L. decoction. Topological analysis of the protein-protein interaction network indicated that compounds, including guanosine, naringenin-7-O-beta-D-glucuronide, noroxyhydrastinine, and chrysophanol 8-O-glucoside, have therapeutic potential for OA. In addition, GAPDH, TNF, TP53, epidermal growth factor receptor, and ESR1 may be key targets for the treatment of OA, primarily involving lipid and atherosclerosis, cellular senescence, IL-17 signaling pathway, and epidermal growth factor receptor tyrosine kinase inhibitor resistance signaling pathways. This method preliminarily identified the chemical composition of O corniculata L. decoction and predicted the active ingredients, potential targets, and signaling pathways of O corniculata L. decoction in treating OA. The findings of this research revealed the potential function of O corniculata L. decoction in anti-inflammation, alongside its ability to promote osteoblast proliferation and differentiation, providing new ideas for the processing of O corniculata L. herbs and related drug development.

Integration of network pharmacology, UHPLC-Q exactive orbitrap HRMS technique and metabolomics to elucidate the active ingredients and mechanisms of compound danshen pills in treating hypercholesterolemic rats

Ethnopharmacological relevanceHypercholesterolemia (HLC) was a key risk factor for cardiovascular disease (CVD) characterized by elevated cholesterol levels, particularly LDL. While traditional Chinese medicine preparations Compound Danshen Pills(CDP) has been clinically used for hypercholesterolemia and coronary heart disease, its specific therapeutic effect on HLC remains understudied, necessitating further investigation into its mechanisms. Aim of the studyThe aim of this study was to explore the potential of CDP in treating HLC and elucidate its underlying mechanisms and active components. Materials and methodsA hypercholesterolemic lipemia rat model induced by a high-fat diet was employed. Network pharmacology combined with UHPLC-Q exactive orbitrap HRMS technique was used to predict the active components, targets and mechanisms of CDP for HLC. Histological analysis and serum biochemical assays were used to assess the therapeutic effect of CDP and its main active ingredient Sa B on hypercholesterolemic lipemia rat model. Immunofluorescence assays and western blotting were used to verify the mechanism of CDP and Sa B in the treatment of HLC. Metabolomics approach was used to demonstrate that CDP and Sa B affected the metabolic profile of HLC. ResultsOur findings demonstrated that both CDP and its main active ingredient Sa B significantly ameliorated hypercholesterolemic lipemic lesions, reducing levels of TC, LDL, AST, ALT, and ALP. Histological analysis revealed a decrease in lipid droplet accumulation and collagen fiber deposition in the liver, as well as reduced collagen fiber deposition in the aorta. Network pharmacology predicted potential targets such as PPARα and CYP27A1. Immunofluorescence assays and western blotting confirmed that CDP and Sa B upregulated the expression of Adipor1, PPARα and CYP27A1. Metabolomics analyses further indicated improvements in ABC transporters metabolic pathways, with differential metabolites such as riboflavin, taurine, and choline showed regression in levels after CDP treatment and riboflavin, L-Threonine, Thiamine, L-Leucine, and Adenosine showed improved expression after Sa B treatment. ConclusionCDP and Sa B have been shown to alleviate high-fat diet-induced hypercholesterolemia by activating the PPAR pathway and improving hepatic lipid metabolism. Our study demonstrated, for the first time, the complex mechanism of CDP, Sa B in the treatment of hypercholesterolemia at the protein and metabolic levels and provided a new reference that could elucidate the pharmacological effects of traditional Chinese medicine on hypercholesterolemia from multiple perspectives.