Additional file 1 of Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation

Additional file 1: Table S1. Includes detailed information of all enzyme-linked immunosorbent assay kits. Table S2. Includes 672 putative target genes of CRT predicted using ETCM database and TCMIP v2.0 platform. Table S3. Includes 3472 DKD-related genes from Human Phenotype Ontology (HPO), DisGeNet and Drugbank databases. Table S4. Includes enrichment results of clinical symptoms of 390 CRT putative targets. Table S5. Includes enrichment results of functional modules of 390 CRT putative targets. Table S6. Includes 231 candidate targets of CRT against DKD in “Disease Gene-Drug Target” interaction networks based on calculated network topological features. Table S7. Includes enrichment results of functional modules of 231 CRT candidate targets

DataSheet1_Disease-Modifying Anti-rheumatic Drug Prescription Baihu-Guizhi Decoction Attenuates Rheumatoid Arthritis via Suppressing Toll-Like Receptor 4-mediated NLRP3 Inflammasome Activation.docx

As a traditional Chinese medicine-originated disease-modifying anti-rheumatic drug prescription, Baihu-Guizhi decoction (BHGZD) is extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic efficacy. Mechanically, our previous data indicated that BHGZD may ameliorate RA partially by restoring the balance of the “inflammation-immune” system through regulating the TLR4-c-Fos-IL2-TNF-alpha axis. Toll-like receptor 4 (TLR4) has been revealed to be involved in the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex. Thus, the aim of the current study was to determine the regulatory effects of BHGZD on the TLR4–mediated inflammasome activation during RA progression based on the modified adjuvant-induced arthritis model (AIA-M) and the lipopolysaccharide/adenosine triphosphate (LPS/ATP)–induced pyroptosis cellular models. As a result, oral administration of BHGZD exhibited prominent improvement in the disease severity of AIA-M rats, such as reducing the redness and swelling of joints, arthritis incidence, arthritic scores, and diameter of the limb and increasing pain thresholds. In line with the in vivo findings, BHGZD treatment effectively inhibited the LPS/ATP–induced pyroptosis of both Raw264.7 macrophage and MH7A cells in vitro by reducing pyroptotic cell death morphology (swollen cells) and decreasing propidium iodide–positive and terminal deoxynucleotidyl transferase–mediated dUTP-fluorescein nick end labeling (TUNEL)–positive cells. Notably, the increased expression levels of TLR4, NLRP3, interleukin 1β, and interleukin 18 proteins and the elevated activities of caspase-1 and lactic dehydrogenase in in vivo and in vitro disease models were markedly reversed by the treatment with BHGZD. In conclusion, the above findings proved the immunomodulatory and anti-inflammatory activities of BHGZD, especially in pyroptosis, which may be attributed to the activation of TLR4–mediated NLRP3 inflammasome signaling.</p

DataSheet_1_A Novel Drug Combination of Mangiferin and Cinnamic Acid Alleviates Rheumatoid Arthritis by Inhibiting TLR4/NFκB/NLRP3 Activation-Induced Pyroptosis.pdf

Growing evidence shows that Baihu-Guizhi decoction (BHGZD), a traditional Chinese medicine (TCM)-originated disease-modifying anti-rheumatic prescription, may exert a satisfying clinical efficacy for rheumatoid arthritis (RA) therapy. In our previous studies, we verified its immunomodulatory and anti-inflammatory activities. However, bioactive compounds (BACs) of BHGZD and the underlying mechanisms remain unclear. Herein, an integrative research strategy combining UFLC-Q-TOF-MS/MS, gene expression profiling, network calculation, pharmacokinetic profiling, surface plasmon resonance, microscale thermophoresis, and pharmacological experiments was carried out to identify the putative targets of BHGZD and underlying BACs. After that, both in vitro and in vivo experiments were performed to determine the drug effects and pharmacological mechanisms. As a result, the calculation and functional modularization based on the interaction network of the “RA-related gene–BHGZD effective gene” screened the TLR4/PI3K/AKT/NFκB/NLRP3 signaling-mediated pyroptosis to be one of the candidate effective targets of BHGZD for reversing the imbalance network of “immune-inflammation” during RA progression. In addition, both mangiferin (MG) and cinnamic acid (CA) were identified as representative BACs acting on that target, for the strong binding affinities between compounds and target proteins, good pharmacokinetic features, and similar pharmacological effects to BHGZD. Notably, both BHGZD and the two-BAC combination of MG and CA effectively alleviated the disease severity of the adjuvant-induced arthritis-modified rat model, including elevating pain thresholds, relieving joint inflammation and bone erosion via inhibiting NF-κB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream caspase-1, the reduced release of IL-1β and IL-18, and the modulation of GSDMD-mediated pyroptosis. Consistent data were obtained based on the in vitro pyroptosis cellular models of RAW264.7 and MH7A cells induced by LPS/ATP. In conclusion, these findings offer an evidence that the MG and CA combination identified from BHGZD may interact with TLR4/PI3K/AKT/NFκB signaling to inhibit NLRP3 inflammasome activation and modulate pyroptosis, which provides the novel representative BACs and pharmacological mechanisms of BHGZD against active RA. Our data may shed new light on the mechanisms of the TCM formulas and promote the modernization development of TCM and drug discovery.</p

Video_4_Working Memory Capacity of Biological Motion’s Basic Unit: Decomposing Biological Motion From the Perspective of Systematic Anatomy.WMV

Many studies have shown that about three biological motions (BMs) can be maintained in working memory. However, no study has yet analyzed the difficulties of experiment materials used, which partially affect the ecological validity of the experiment results. We use the perspective of system anatomy to decompose BM, and thoroughly explore the influencing factors of difficulties of BMs, including presentation duration, joints to execute motions, limbs to execute motions, type of articulation interference tasks, and number of joints and planes involved in the BM. We apply the change detection paradigm supplemented by the articulation interference task to measure the BM working memory capacity (WMC) of participants. Findings show the following: the shorter the presentation duration, the less participants remembered; the more their wrist moved, the less accurate their memory was; repeating verbs provided better results than did repeating numerals to suppress verbal encoding; the more complex the BM, the less participants remembered; and whether the action was executed by the handed limbs did not affect the WMC. These results indicate that there are many factors that can be used to adjust BM memory load. These factors can help sports psychology professionals to better evaluate the difficulty of BMs, and can also partially explain the differences in estimations of BM WMC in previous studies.</p

Video_3_Working Memory Capacity of Biological Motion’s Basic Unit: Decomposing Biological Motion From the Perspective of Systematic Anatomy.WMV

Many studies have shown that about three biological motions (BMs) can be maintained in working memory. However, no study has yet analyzed the difficulties of experiment materials used, which partially affect the ecological validity of the experiment results. We use the perspective of system anatomy to decompose BM, and thoroughly explore the influencing factors of difficulties of BMs, including presentation duration, joints to execute motions, limbs to execute motions, type of articulation interference tasks, and number of joints and planes involved in the BM. We apply the change detection paradigm supplemented by the articulation interference task to measure the BM working memory capacity (WMC) of participants. Findings show the following: the shorter the presentation duration, the less participants remembered; the more their wrist moved, the less accurate their memory was; repeating verbs provided better results than did repeating numerals to suppress verbal encoding; the more complex the BM, the less participants remembered; and whether the action was executed by the handed limbs did not affect the WMC. These results indicate that there are many factors that can be used to adjust BM memory load. These factors can help sports psychology professionals to better evaluate the difficulty of BMs, and can also partially explain the differences in estimations of BM WMC in previous studies.</p

Video_1_Working Memory Capacity of Biological Motion’s Basic Unit: Decomposing Biological Motion From the Perspective of Systematic Anatomy.WMV

Many studies have shown that about three biological motions (BMs) can be maintained in working memory. However, no study has yet analyzed the difficulties of experiment materials used, which partially affect the ecological validity of the experiment results. We use the perspective of system anatomy to decompose BM, and thoroughly explore the influencing factors of difficulties of BMs, including presentation duration, joints to execute motions, limbs to execute motions, type of articulation interference tasks, and number of joints and planes involved in the BM. We apply the change detection paradigm supplemented by the articulation interference task to measure the BM working memory capacity (WMC) of participants. Findings show the following: the shorter the presentation duration, the less participants remembered; the more their wrist moved, the less accurate their memory was; repeating verbs provided better results than did repeating numerals to suppress verbal encoding; the more complex the BM, the less participants remembered; and whether the action was executed by the handed limbs did not affect the WMC. These results indicate that there are many factors that can be used to adjust BM memory load. These factors can help sports psychology professionals to better evaluate the difficulty of BMs, and can also partially explain the differences in estimations of BM WMC in previous studies.</p

Video_2_Working Memory Capacity of Biological Motion’s Basic Unit: Decomposing Biological Motion From the Perspective of Systematic Anatomy.WMV

Many studies have shown that about three biological motions (BMs) can be maintained in working memory. However, no study has yet analyzed the difficulties of experiment materials used, which partially affect the ecological validity of the experiment results. We use the perspective of system anatomy to decompose BM, and thoroughly explore the influencing factors of difficulties of BMs, including presentation duration, joints to execute motions, limbs to execute motions, type of articulation interference tasks, and number of joints and planes involved in the BM. We apply the change detection paradigm supplemented by the articulation interference task to measure the BM working memory capacity (WMC) of participants. Findings show the following: the shorter the presentation duration, the less participants remembered; the more their wrist moved, the less accurate their memory was; repeating verbs provided better results than did repeating numerals to suppress verbal encoding; the more complex the BM, the less participants remembered; and whether the action was executed by the handed limbs did not affect the WMC. These results indicate that there are many factors that can be used to adjust BM memory load. These factors can help sports psychology professionals to better evaluate the difficulty of BMs, and can also partially explain the differences in estimations of BM WMC in previous studies.</p