Combinatorial Chemistry & High Throughput Screening - Volume 24, Issue 7, 2021

Aim and Objective: To evaluate the efficacy and safety of Chinese herbal medicines for promoting blood circulation and removing blood stasis (PBCRBSM) for preventing deep venous thrombosis (DVT) after total hip arthroplasty (THA). Materials and Methods: The databases were searched for studies comparing the preventive abilities of PBCRBSM and Western medicine, such as low molecular weight heparin (LMWH), rivaroxaban, and aspirin, as well as for randomized controlled trials on DVT after THA. Data were analyzed using RevMan 5.3 software. Results: A total of 3254 randomized controlled trials were included, including 1630 cases in the experimental group and 1624 cases in the control group. Meta-analysis showed that compared with Western medicine, PBCRBSM reduced the incidence of DVT (OR=0.38, 95% CI [0.30, 0.48], P < 0.001); prolonged activated partial thromboplastin time (APTT) (SMD=0.44, 95% CI [0.35, 0.53], P < 0.001); reduced D-dimer (SMD=-0.75, 95% CI [-0.84,-0.65], P < 0.001), FIB (SMD=-0.61, 95% CI [-0.72, -0.50], P < 0.001), blood viscosity (P<0.01), circumference difference in lower extremities (P<0.01), venous blood flow velocity (SMD=0.97, 95% CI [0.77, 1.16], P < 0.001), and drainage volume (SMD=-1.53, 95% CI [-1.71, -1.35], P < 0.001); and reduced adverse reactions (OR = 0.32, 95% CI [0.19, 0.56], P < 0.001). There was no significant difference in prolonging prothrombin time (PT) between traditional Chinese medicine and Western medicine (SMD = 0.07, 95% CI [-0.0.01). 3, 0.16], P > 0.05. Conclusion: PBCRBSM is an effective method for preventing DVT after THA and has fewer adverse effects.

Background: Clinical outcomes after rotator cuff repair associated with diabetes mellitus (DM) are generally favorable, but no study has attempted to establish the influence of DM on outcomes after rotator cuff repair. Purpose: To conduct a meta-analysis of clinical studies evaluating patient outcomes between people with DM and people without DM after rotator cuff repair. Study Design: Meta-analysis. Methods: A literature search of the Embase, PubMed, and Cochrane Library databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Cohort studies and case-control studies about clinical outcomes after rotator cuff repair comparing people with DM and people without DM were included. Statistical analysis was performed with RevMan (v 5.3.3). Results: Nine clinical studies that met the inclusion criteria were identified and included a total of 314 patients treated with DM and 1092 patients without DM. The failure rate was significantly higher in the DM group than in Non-DM group (23.97% compared with 16.60%, OR: 2.39; 95% CI, 1.69–3.37; p < 0.001). The postoperative retear rate and showed a significant difference between the two groups (24.5% and 13.7%; OR: 2.41; 95% CI, 1.57–3.71; p<0.001). The DM group showed a higher rate of postoperative unhealed cuff than the Non-DM group(41.81% and 25.23%; OR: 2.14; 95% CI, 1.69–3.37; p=0.01).Postoperative Range of motion(ROM) at 12 months after surgery show a significant difference in the range of external rotation between two groups (WMD: -6.02; 95% CI, -7.54 to -4.50; p<0.001). The preoperative Japanese Orthopaedic Association (JOA) score, the comparison of pre- and post-operative JOA scores showed a significant difference in the DM and Non-DM group(p<0.001). The postoperative JOA score, the pre- and post-operative muscle strength, the pre- and post-operative visual analog scale (VAS) show significant difference between the DM and Non-DM group(p<0.001). The postoperative infection rates, the rates of postoperative shoulder stiffness, the preoperative ROM, the postoperative ROM at 6 months, the postoperative ROM at 12 months of forward flexion and abduction, the American Shoulder and Elbow Surgeons score, the University of California, Los Angeles scores, and the preoperative Constant-Murley scores show no significant difference between the two groups. Conclusion: This meta-analysis indicates that DM may be relative to a higher rate of shoulder retear and cuff unhealing. However, patients with DM can achieve great clinical outcomes after cuff repair, compared to patients without DM.

Background: The manual identification of Fructus Crataegi processed products is inefficient and unreliable. Therefore, efficient identification of the Fructus Crataegis’ processed products is important. Objective: In order to efficiently identify Fructus Crataegis processed products with different odor characteristics, a new method based on an electronic nose and convolutional neural network is proposed. Methods: First, the original smell of Fructus Crataegis processed products is obtained by using the electronic nose and then preprocessed. Next, feature extraction is carried out on the preprocessed data through convolution pooling layer LCP1, convolution pooling layer LCP2 and a full connection layer LFC. Thus, the feature vector of the processed products can be obtained. Then, the recognition model for Fructus Grataegis processed products is constructed, and the model is trained to obtain the optimized parameters: filters F1 and F2, bias vectors B1, B2, B3, and B4, matrices M1 and M2. Finally, the features of the target processed products are extracted through the trained parameters to achieve accurate prediction. Results: The experimental results show that the proposed method has higher accuracy for the identification of Fructus Crataegis processed products, and is competitive with other machine learning based methods. Conclusion: The method proposed in this paper is effective for the identification of Fructus Crataegi processed products.

Background: As artificial intelligence and big data analysis develop rapidly, data privacy, especially patient medical data privacy, is getting more and more attention. Objective: The study aims to strengthen the protection of private data while ensuring the model training process; this article introduces a multi-Blockchain-based decentralized collaborative machine learning training method for medical image analysis. In this way, researchers from different medical institutions are able to collaborate to train models without exchanging sensitive patient data. Methods: Partial parameter update method is applied to prevent indirect privacy leakage during model propagation. With the peer-to-peer communication in the multi-Blockchain system, a machine learning task can leverage auxiliary information from another similar task in another Blockchain. In addition, after the collaborative training process, personalized models of different medical institutions will be trained. Results: The experimental results show that our method achieves similar performance with the centralized model-training method by collecting data sets of all participants and prevents private data leakage at the same time. Transferring auxiliary information from similar task on another Blockchain has also been proven to effectively accelerate model convergence and improve model accuracy, especially in the scenario of absence of data. Personalization training process further improves model performance. Conclusion: Our approach can effectively help researchers from different organizations to achieve collaborative training without disclosing their private data.

Aim and Objective: Cell death is a main pathological change in brain ischemia. Astragalus membranaceus (Ast) and ligustrazine (Lig), as traditional Chinese herbs, have a protective effect against ischemia-reperfusion injury. We aim to find whether the underlying protective mechanism of Astragalus membranaceus and ligustrazine against Oxygen–glucose deprivation/reoxygenation (OGD/R) -induced injury in RBMECs is related to PKCδ/MARCKS pathway. Materials and Methods: OGD/R preconditioning was instituted in rat brain microvascular endothelial cells (RBMECs). The survival and apoptosis of RBMECs were detected by a Cell Counting Kit-8 and TUNEL staining; PKCδ/MARCKS and MMP9 expression were examined by immunofluorescence, western blot and quantitative real-time PCR. Results: OGD/R stimulation significantly increased RBMEC apoptosis, whereas Ast+Lig, Rottlerin or Ast+Lig+Rottlerin treatment evidently reduced cellular apoptosis and increased cell viability (P <0.05). Furthermore, Ast+Lig, Rottlerin or Ast+Lig+Rottlerin treatment significantly reduced mRNA expression levels of PKCδ/MARCKS and MMP9 (P <0.05), compared to OGD/R control group. Moreover, Ast+Lig, Rottlerin or Ast+Lig+Rottlerin treatment evidently reduced protein expression levels of PKCδ, MMP9, and MARCKS (P <0.05), compared to OGD/R control group, detected by western blotting or immunofluorescence. Conclusion: The administration of Astragalus membranaceus and ligustrazine protected RBMECs against OGD/R-induced apoptosis. PKCδ/MARCKS and MMP9 expression were significantly increased after OGD/R stimulation, while Astragalus membranaceus and ligustrazine treatment evidently suppressed. Collectively, Astragalus membranaceus and ligustrazine play protective effects against OGD/R-induced injury in RBMECs through regulating PKCδ/MARCKS pathway to inhibit MMP9 activation.

Background: Novel coronavirus pneumonia (NCP), or coronavirus disease 2019 (COVID-19), is a worldwide health threat that has affected millions of people globally. Traditional Chinese medicine (TCM) has been introduced for the treatment of COVID-19. However, efficacy differs among herbal medicines, and the ideal prescription pattern for TCM herbal formulae for COVID-19 treatment needs to be explored. Therefore, the data mining method has been used in this study to analyze the TCM prescription pattern for COVID-19. Objective: The aim of this study was to analyze the TCM prescription pattern in Regional Schemes in China for COVID-19 in order to provide a new reference for the use of TCM in COVID-19 treatment. Methods: By searching the TCM treatment protocols of COVID-19 in 23 Regional Schemes, TCM syndromes and herbal medicines were analyzed by data mining. The Ancient and Modern Medical Case Cloud Platform (V2.1 personal Edition) was used to perform frequency statistics, correlation analysis, and cluster analysis. A total of 82 TCM syndromes and 171 Chinese herbal medicines were found. The course of the disease can be divided into the early stage, middle stage, severe stage, and recovery stage. Results: In the early stage, the focus is primarily on resolving dampness, dispelling cold, and diffusing the lungs. In the middle stage, the treatment priority is clearing heat and resolving toxins, promoting lung function, and relieving asthma. In the severe stage, the focus is on tonifying Qi, restoring Yang, and relieving the depletion of Yin and Yang. In the recovery stage, the main treatment is to invigorate the spleen and regulate Qi, tonify Qi, nourish Yin, and clear residual disease. There are certain differences between the Regional Schemes and the Nation Schemes, but the core prescription pattern of the former is consistent with the latter. The effectiveness of these 171 Chinese herbs include but are not limited to inhibiting COVID-19, strengthening immune system function, preventing heart failure, acting as antioxidants, oxidative stress inhibitory effects, maintaining organ function, and improving leukocyte survival. Conclusion: This study may help to improve understanding of TCM herbal prescription pattern, practices, reveal the efficacy of combinations of Chinese herbs, and provide new ideas for TCM treatment for COVID-19.

Background: Shoulder-hand syndrome (SHS) refers to a syndrome causing sudden edema, shoulder pain and limited hand function. Qingpeng ointment, a kind of Tibetan medicine, can reduce swelling, relieve pain, tonify stagnation and clear the meridians, which is consistent with the pathological mechanism of SHS after stroke. Therefore, if clinical trials can be used to explore the effectiveness of Qingpeng ointment for the treatment of poststroke SHS and promote its application in clinical medicine, it may prove the specific significance for the treatment of poststroke SHS poststroke SHS. Objective: The aim of the study was to investigate the clinical efficacy and safety of Qingpeng ointment in the treatment of poststroke SHS and to provide an objective basis for a better therapeutic treatment for poststroke SHS. Methods: A prospective, randomized, controlled study was conducted. This study recruited 120 patients with poststroke SHS who met the inclusion criteria. They were randomized into the treatment group and the control group, with 60 patients allocated to each group. The treatment group received routine medical treatment and rehabilitative care after using the Qingpeng ointment, while the patients in the control group received only routine treatment without the ointment. All patients received clinical assessment with the Visual Analogue Scale (VAS), measurement of the range of motion (ROM) of the upper-limb joints, the Fugl-Meyer Assessment of Upper Extremity (FMA-U) and the Modified Barthel Index Score (MBI) before and after the whole treatment. Results: After 4 weeks of treatment, the VAS scores of both the groups decreased significantly (P #156;0.05), and the difference between the two groups was statistically significant (P < 0.05). No statistical significance was observed for the difference between the treatment group and control group in terms of the FMA-U and MBI scores and the forward bend, backward, outstretch, external rotation and pronation angles after treatment. The increases in the values of VAS, FMA-M and MBI in the treatment group were greater than those in the control group, and the difference was statistically significant (P < 0.05). The increases in the values of the forward bend, outreach and external rotation angles in the treatment group were greater than those in the control group, and the difference was statistically significant (P < 0.05). Conclusion: The treatment group showed better results than the control group in terms of the relief of pain symptoms, the improvement of motor function and the improvement of the activities of daily living for patients with shoulder-hand syndrome after cerebral hemorrhage. Qingpeng ointment was found to be effective and safe for treating poststroke SHS.

Background: Recent studies have shown that patients with psoriasis, a chronic inflammatory skin disorder that may accompany the serious systemic disease, are at risk of developing sudden sensorineural hearing loss. The pathogenesis remains unclear, and the mechanisms of this disorder are difficult to explore in the clinical setting due to psoriasis hearing loss’s infrequent incidence. Here, we aimed to identify key candidate genes that may be involved in the pathogenesis of psoriatic hearing loss. Methods: In the present study, through online databases and literature review, we utilized microRNA-mRNA network analysis and gene ontology annotation analysis, coupled with experimental data from clinical samples, to investigate the relationship between psoriasis and hearing loss. Results: We identified nine miRNAs implicated in both psoriasis and the auditory system. By using bioinformatics techniques, 12 target genes were identified. Finally, the gap junction beta-2 protein (GJB2) was found to be relevant to both psoriasis and hearing loss. Also, the expression of connexin 26 (Cx26), encoded by GJB2, was significantly downregulated in psoriatic patients’ plasma (p < 0.0001) and was negatively correlated with psoriasis area and severity index (PASI) clinical score (r, −0.286; p = 0.036). Conclusion: GJB2 is a potential candidate gene for hearing loss in psoriasis.

Aim and Objective: Inflammation-related changes in peripheral blood cells and blood proteins are prognostic factors for survival in hepatocellular carcinoma (HCC), but their usefulness is limited by an active bacterial infection. This study investigated whether infection interfered with the predictive value of serglycin, a proteoglycan found in hematopoietic cells, on survival in HCC. Materials and Methods: Patients with hepatitis B virus (HBV)-induced HCC, 100 without and 30 with a bacterial infection, and 30 healthy adult controls were enrolled retrospectively. Baseline clinical data collected before treatment with transarterial chemoembolization (TACE) was evaluated, and serglycin expression was assayed by flow cytometry. Receiver operating characteristic (ROC) curve analysis identified serglycin cutoff values for patient stratification. Cox regression and Kaplan–Meier analyses were performed to identify predictors of overall survival (OS). Results: Serglycin levels in peripheral blood cells were higher in both groups of HCC patients than in the control group. Cholinesterase, lung metastasis, average neutrophil serglycin fluorescence intensity, and aspartate aminotransferase levels were associated with survival risk. Barcelona Clinic Liver Cancer stage A was associated with a good prognosis of OS. Conclusion: The intensity of serglycin fluorescence in peripheral neutrophils was independently predictive of survival in HCC, and its value was not limited by a bacterial infection. The method presented here is a simple and feasible way to predict prognosis in HCC patients with TACE.

Background: Converging evidence indicates that the glutamatergic system and glia are directly implicated in the pathophysiology of depression. Clinical studies indicate that electroacupuncture (EA) has anti-depressant-like effects with low side effects for depression. However, the underlying antidepressant mechanism of acupuncture remains obscure. Methods: Chronic unpredictable mild stress (CUMS)-induced depressive rats were used to induce depressive-like behavior and evaluated by the weight change, open field test, sucrose preference test, and novelty suppressed feeding test. EA, NMDA receptor subunit 2A antagonist (NR2A RA) or NMDA receptor subunit 2B antagonist (NR2B RA) was used for comparison. Highperformance liquid chromatography (HPLC) was performed to detect the content of hippocampal glutamate, while western blot was performed for the hippocampal protein expression levels of calcium/calmodulin-dependent protein kinase II (CaMKII), Bax, caspase 3 and B-cell lymphoma-2 (Bcl-2). The distribution of glutamate ionotropic receptor NMDA type subunit 2A (NR2A), neuronal nuclear protein (NeuN), glutamate ionotropic receptor NMDA type subunit 2B (NR2B), and glial fibrillary acidic protein (GFAP) were detected by immunofluorescence. Results: Significant depression behavior (reduced body weight and sucrose preference, increased feeding and immobility time) was produced in CUMS-induced depressive rats, which was reversed significantly by EA. EA decreased hippocampal glutamate level. EA led to a significant decrease in expression levels of Bax, caspase 3, and CaMK II accompanied by increased Bcl-2 expression levels. Furthermore, EA significantly increased NR2A expression level as well as decreased NR2B expression level in the hippocampus. Conclusion: EA ameliorated depression-like behavior in CUMS rats, which might be mediated, at least in part, by regulating the glutamate, NMDA receptors, and apoptosis in the hippocampus.

Structural biology develops rapidly with time. The static structure analysis of biomaterials is not enough to satisfy the studies of their functional mechanisms, with a huge obstacle for the dynamic process of biological complexes. The rapid development of cryo-electron microscopy (cryo-EM) technology makes it possible to observe the near-atomic resolution structures and dynamic nature of biological macromolecules, in the fields of dynamic characteristics of proteins, protein-protein interactions, molecular recognition, and structure-based design. In this review, we systematically elaborate the contribution of cryo-EM technology in the field of biomaterials such as ribosome motion, membrane protein structure and conformational space, dynamic transmission within the plasma membrane and clinical applications. We also put forward a new standpoint in the development of cryo-EM technology.

Stimulated emission depletion (STED) microscopy has become a useful tool for visualization and dynamic monitoring at an ultra-high resolution in biological research and material science. For STED technology, fluorescent probes are irreplaceable in the imaging process. Among these probes, organic fluorescent probes have superior photo-stability, high brightness, large Stokes’ shifts and excellent biocompatibility, thus are widely applied in STED microscopy. Based on this consideration, this review presents the recent advances on organic fluorescent probes for STED microscopy, including typical organic fluorescent probes, aggregation-induced emission luminogens (AIEgens), polymer dots, and other nanoparticles. The applications of organic fluorescent probes in biological imaging, such as in live-cell, live-tissue, and in vivo imaging, as well as in material monitoring at the nanoscale using STED microscopy, are also included. This review provides the guidelines for the design of new materials that can be used to enhance the imaging performance of STED microscopy, thus leading to real-world applications.

The unprecedented growth in the area of QSAR has completely changed the landscape of drug discovery. QSAR techniques quantitatively correlate the associations between chemical structure alterations and respective changes in biological activity, thereby playing a major role in improving the potency, efficacy and selectivity of the lead compounds in drug design. In this review, authors have summarized the role of QSAR in drug discovery, especially with respect to lead optimization and drug-receptor interactions. The recent trends in the usage of 3D-QSAR to understand Protein-Protein Interactions (PPIs) have been explored. Specifically, the latest advances in the concepts of chemical Space (CS) and chemography have been examined in detail. Also, the authors have tried to present the current limitations and challenges in this field. The authors agree with the prevalent view that the models must be systematically validated both internally as well as externally to strengthen the hit rates in the experiments. It is important to apply the ‘in cerebro-in silico’ approach that entails choosing the method specific to the target–ligand system.

Background: With increasing applications and development of high-throughput sequencing, knowledge of the primary structure of RNA has expanded exponentially. Moreover, the function of RNA is determined by the secondary or higher RNA structure, and similar structures are related to similar functions, such as the secondary clover structure of tRNA. Therefore, RNA structure alignment is an important subject in computational biology and bioinformatics to predict function accurately. However, the traditional RNA structure alignment algorithms have some drawbacks such as high complexity and easy loss of secondary structure information. Objective: To study R,,NA secondary structure alignment according to the shortcomings of existing secondary structure alignment algorithms and the characteristics of RNA secondary structure. Methods: We propose a new digital sequence RNA structure representation algorithm named “DSARna”. Then based on a dynamic programming algorithm, the scoring matrix and binary path matrix are simultaneously constructed. The backtracking path is identified in the path matrix, and the optimal result is predicted according to the path length. Conclusions: Upon comparison with the existing SimTree algorithm through experimental analysis, the proposed method showed higher accuracy and could ensure that the structural information is not easily lost in terms of improved specificity, sensitivity, and the Matthews correlation coefficient.

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) that erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted to the quest of the medicine that can cure COVID-19. Objective: Existing antivirals, such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine, have been repurposed to fight the current coronavirus epidemic. Exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Methods: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs, including antivirals and antimalarials, to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Aims & Objective: Coronavirus Disease 2019 (COVID-19) caused by the human coronavirus 2019 (HCoV-19, also known as SARS-CoV-2) infection is currently in a global outbreak. COVID-19 has posed a huge threat to public health and economic stability worldwide. CR3022, a human monoclonal neutralizing antibody isolated from a Severe Acute Respiratory Syndrome (SARS) recovery patient, was confirmed to be able to bind the S protein of HCoV-19 with a certain degree of neutralizing activity. Crystal structural information indicated that CR3022 could bind to the epitope on the receptor binding domain (RBD) of HCoV-19, whose epitope consists of 28 amino acids, and 24 of them are conserved in SARS-CoV of SARS. However, the crystal structure is only a static conformation at a certain moment in time, and it cannot provide dynamic details of the interaction between antigen and antibody. Methods: In this study, molecular dynamics (MD) simulation combined with MM/PBSA and CAS methods were performed to investigate the mechanism of binding of CR3022 against SARS-CoVRBD and HCoV-19-RBD in order to determine their holographic dynamic information. Results: It was found that the CR3022-SARS-CoV-RBD complex was more stable during 100ns MD run than that of the CR3022-HCoV-19-RBD system. There were common conservative amino acids on the β2 sheet of RBD, including Tyr369, Phe377, Lys378, Tyr380, Gly381, Lys386, Leu390 and others. These conservative amino acids play significant roles in the binding process of CR3022 antibody against SARS-CoV-RBD and HCoV-19-RBD. It was also found that the binding mode of CR3022 to its native target SARS-CoV-RBD is more comprehensive and uniform. Moreover, the β2 sheet residue Thr385 and non-β2 sheet residues Arg408 and Asp428 of the CR3022-SARS-CoV-RBD system were found to be crucial for their binding affinities, thus forming a special conformational epitope. However, these key amino acids are not present in the CR3022-HCoV-19-RBD system. The binding mode of CR3022 and HCoV-19-RBD is similar to that of SARS-CoV-RBD, but the deficiency of crucial hydrogen-bonds and salt-bridges. Therefore, the binding of CR3022 and HCoV-19-RBD only draws on the partial mode of the binding of CR3022 and SARS-CoV-RBD, so there is a loss of affinity. Conclusion: Thus, in order to better fight the epidemic of COVID-19 with the CR3022 antibody, this antibody needs to further improve the neutralization efficiency of HCoV-19 through mutation of it’s CDR region.

Alzheimer's disease is an age-related neurodegenerative disease. The factors causing Alzheimer's disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer's disease progression. Among them, neuroinflammation, oxidative stress, and apoptosis play a major role because of the accumulation of extracellular amyloid-beta peptides. Here, the clearance of amyloid beta-peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta-peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines, and the complement system also has a major role in Alzheimer's disease. The physiological clearance pathways involved in amyloid beta-peptide are glymphatic, vascular, and immune pathways. Amyloid precursor protein, low-density lipoprotein receptor-related protein 1, receptor for the advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines, and microglia are involved in amyloid beta-peptide clearance pathways across the blood-brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid-beta agglomeration. This insoluble amyloid-beta leads to a neurodegenerative cascade and neuronal cell death occurs. Studies had shown that disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for Alzheimer'sdisease via focusing on pathways for amyloid-beta clearance are discussed.

Background: Rheum palmatum L. (RpL) is a traditional Chinese medicine commonly used clinically. However, there was no systematic research to elucidate the mechanisms of RpL acting on COPD. Objective: To explore the potential mechanisms against COPD based on network pharmacology. Methods: The active compounds of RpL were retrieved from TCMSP database, and their corresponding targets were obtained through TCMSP and STITCH databases. COPD-related targets were identified from the TTD, GeneCards and MalaCards database. Drug-disease genes were obtained through intersection analysis, and the correlation between these genes and COPD was analyzed. After that, a protein-protein interaction network was constructed and enrichment analysis was performed. Then, key targets were obtained according to the network topology attributes analysis. Finally, the Auto dock vina 1.1.2 was used for molecular docking to verify the binding ability between the active compounds and key targets. Results: There were 8 active compounds and 90 corresponding targets were identified in RpL. A total of 4502 COPD-related targets were obtained from databases. After cross-analysis, 81 drug-disease targets were obtained. Drug-disease targets mainly regulated apoptosis and inflammatory responses and participated in related signal pathways. Besides, 28 key genes were obtained from the network topology analysis. TP53, TNF, NFKB1, VEGFA, MMP9, and MMP1 were selected to dock with the compounds. The results of molecular docking showed that the above targets have different affinities with the 8 active compounds of RpL. Conclusion: The mechanisms of RpL acting on COPD were mainly related to the regulation of apoptosis, inflammatory response, and airway remodeling.