Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Radix Paeoniae Rubra Against Glioma.

Glioma has a high mortality and can hardly be completely cured. Radix Paeoniae Rubra (RPR) is a prevalent component in traditional Chinese medicine used for tumor treatments. We explored the mechanism of RPR in treating glioma using network pharmacology and experiments. A network pharmacology approach was used to screen active ingredients, targets of RPR and glioma. We then constructed a herb-active ingredient-target-pathway network and conducted protein-protein interaction (PPI) network analysis, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was also performed. Using CCK-8, colony formation, and xenograft experiments, we evaluated the effect of RPR on glioma. The involved pathway and proteins were identified by Western blot. From public databases, we identified nine active RPR ingredients and 40 overlapping targets among 109 RPR targets and 1360 glioma-associated targets. The PPI analysis revealed ten targets, such as AKT1, TP53, and VEGFA, which were identified as hub genes. The results from GO and KEGG analysis highlighted the involvement of the PI3K/AKT pathway. A herb-active ingredient-target-pathway network was constructed. By docking molecular structures, six suitable conformations have been identified. The RPR extract demonstrated anti-tumor properties by inhibiting glioma cell proliferation in vitro and in vivo, likely achieved by suppressing the phosphorylation of the PI3K/AKT signaling pathway. RPR concurrently downregulated the phosphorylation level of AKT1 and the protein expression level of VEGFA, while upregulating the expression of P53 in the U251 cell line. Utilizing network pharmacology and molecular docking, our study not only predicted the impact of RPR on glioma but also delineated the herb-active ingredient-target-pathway network. Experimentally, we confirmed that RPR may exert its anti-tumor properties by inhibiting the phosphorylation of the PI3K/AKT pathway, including AKT1, and by regulating the expression levels of VEGFA and P53.

Effects of 1,4-dihydropyridine derivatives on cell injury and mTOR of HepG2 and 3D-QSAR study.

1,4-dihydropyridine derivatives (1,4-DHPs) are a class of drugs used to treat cardiovascular diseases, but these drugs can cause liver injury. To reveal the toxicity characteristics of these compounds, we used a series of assays, including cell viability, enzyme activity detection, and western blotting, to investigate the toxicity of seven kinds of 1,4-DHPs (0-100 µM) on HepG2 cells and establish 3D-QSAR model based on relevant toxicity data. After HepG2 cells were treated with 1,4-DHPs for 24 h, high-dose (100 µM) 1,4-DHPs decreased cell viability to varying degrees, while ROS and MDA contents were significantly increased, and ATP content was reduced. Moreover, with the concentration of 100 µM 1,4-DHPs (Nimodipine, Nitrendipine, Cilnidipine, and Manidipine) were markedly inhibited the phosphorylation levels of mTOR protein. The results of the 3D-QSAR model showed that the non-cross validation coefficient (R2) and cross validation coefficient (Q2) of the model were 0.982 and 0.652, respectively. Combined with external validation and the Williams diagram, the model showed good predictability and application domain. Based on the CoMSIA 3D contour map, the introduction of large volume and hydrogen bond receptor groups on the carbonyl oxygen side chains of the 1,4-DHPs ring 3- and 5- was beneficial for reducing the toxicity of 1,4-DHPs. The results of this study could supplement information on the cytotoxicity of 1,4-DHPs, and could provide theoretical support for predicting the toxicity of 1,4-DHPs.

Application of Atorvastatin Combined with Ezetimibe in Elderly Patients with Hypertension Combined with T2DM and Analysis of Significance of Changes in Serum Bilirubin Levels During Treatment.

Objective: To investigate the application of atorvastatin (AT) combined with ezetimibe (EZ) in elderly patients with hypertension (HY) combined with type 2 diabetes mellitus (T2DM) and the significance analysis of changes in serum bilirubin levels during treatment. Methods: One hundred and twelve elderly patients with HY combined with T2DM admitted to our hospital from September 2019 to March 2022 were selected and divided into a control group (AT) and a combined group (AT + EZ) according to the random number table method, with 56 cases in each group. It revealed that blood glucose, lipid function, inflammatory factors, and serum bilirubin [(total bilirubin, direct bilirubin (DBIL), indirect bilirubin (IBIL))] were also compared in both groups. The combined group was divided into high and low expression groups according to the mean total bilirubin value, and the incidence of adverse reactions was compared between the two groups. Results: Glucose, lipid function, and inflammatory factors were lower in the combined group than in the control group (P < .05). Total bilirubin, DBIL, and IBIL were higher in the combined group than in the control group (P < .05). The total incidence of adverse reactions in the high expression group was significantly lower than that in the low expression group (12.50% vs. 28.57%, P < .05). Conclusion: AT combined with EZ can effectively improve glucose, lipids, inflammation and upregulate serum bilirubin in patients with HY combined with T2DM.

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders.

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a newly developed technique involves stimulating the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear, with resulting activation of vagal connections to central and peripheral nervous systems. Increasing evidence indicates that maladaptive neural plasticity may underlie the pathology of several pediatric neurodevelopmental and psychiatric disorders, such as autism spectrum disorder, attention deficit hyperactivity disorder, disruptive behavioral disorder and stress-related disorder. Vagal stimulation may therefore provide a useful intervention for treating maladaptive neural plasticity. In the current review we summarize the current literature primarily on therapeutic use in adults and discuss the prospects of applying taVNS as a therapeutic intervention in specific pediatric neurodevelopmental and other psychiatric disorders. Furthermore, we also briefly discuss factors that would help optimize taVNS protocols in future clinical applications. We conclude from these initial findings that taVNS may be a promising alternative treatment for pediatric disorders which do not respond to other interventions.

Transcutaneous auricular vagus nerve stimulation increases eye-gaze on salient facial features and oxytocin release.

Non-invasive, transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) via the ear is used therapeutically in epilepsy, pain, and depression, and may also have beneficial effects on social cognition. However, the underlying mechanisms of taVNS are unclear and evidence regarding its role in social cognition improvement is limited. To investigate the impact of taVNS on social cognition we have studied its effects on gaze toward emotional faces in combination with eye-tracking and on the release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation. A total of 54 subjects were enrolled (49 were included in the final analysis) in a sham-controlled, participant-blind, crossover experiment, consisting of two treatment sessions 1 week apart. In one session participants received 30-min taVNS (tragus), and in the other, they received 30-min sham (earlobe) stimulation with the treatment order counterbalanced. The proportion of time spent viewing the faces and facial features (eyes, nose, and mouth) was measured together with resting pupil size. Additionally, saliva samples were taken for the measurement of oxytocin concentrations by enzyme-linked immunoassay. Saliva oxytocin concentrations increased significantly after taVNS compared to sham stimulation, while resting pupil size did not. In addition, taVNS increased time spent viewing the nose region irrespective of face emotion, and this was positively correlated with increased saliva oxytocin concentrations. Our findings suggest that taVNS biases visual attention toward socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release.

Shenling Baizhu Powder () Ameliorates Pi (Spleen)-Deficiency-Induced Functional Diarrhea in Rats.

OBJECTIVE: To explore the mechanism of Pi (Spleen)-deficiency-induced functional diarrhea (FD) model rats treated by Shenling Baizhu Powder (, SBP). METHODS: Thirty male Sprague-Dawley rats were randomly divided into 5 groups including control, model, low-, medium-, and high-dose SBP groups (SBPLDG, SBPMDG, SBPHDG), 6 rats in each group, respectively. Pi-deficiency-induced FD rats model was developed through Radix et Rhizoma Rhei gavage for 7 days. After modeling, the rats were treated with 3 doses of SBP [0.93, 1.86, and 3.72 g/(kg·d)], and the rats in the control and model groups were given pure water for 7 days. The diarrhea index was calculated. On the 7th and 14th days, the traveled distance of rat was measured by the open field test. Serum D-xylose content was determined by the phloroglucinol method and interleukin (IL)-10 and IL-17 levels were measured using an enzyme-linked immunosorbent assay kit. The content of Treg cells was determined by flow cytometry. RESULTS: Compared with the control group, the diarrhea index and IL-17 level in the model group were significantly higher and the total exercise distance and D-xylose content significantly decreased (P>0.05). The expression of IL-10 in the SBPHDG group was significantly up-regulated, and serum D-xylose level and Treg cells increased significantly compared with the model group (P>0.05). CONCLUSION: High-dose SBP exhibited ameliorating effects against Pi-deficiency induced FD, which might be attributed to its modulations on intestinal absorption function as well as adaptive immunity in mesenteric lymph nodes of rat.

Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor.

Human immunodeficiency virus type 1 (HIV-1) is responsible for the majority of HIV infections worldwide, and we still lack a cure for this infection. Blocking the interaction of HIV-1 and its primary receptor CD4 is one strategy for identifying new anti-HIV-1 entry inhibitors. Here we report the discovery of a novel ligand that can inhibit HIV-1 entry and infection via CD4. Biological and computational analyses of this inhibitor and its analogs, using bioactivity evaluation, Rule of Five (RO5), comparative molecular field analysis (CoMFA)/comparative molecular similarity index analysis (CoMSIA) models, and three-dimensional quantitative structure-activity relationship (3D-QSAR), singled out compound 3 as a promising lead molecule for the further development of therapeutics targeting HIV-1 entry. Our study demonstrates an effective approach for employing structure-based, rational drug design techniques to identify novel antiviral compounds with interesting biological activities.

Assessment of arsenic in colostrum and cord serum and risk exposure to neonates from an island population in China.

Arsenic (As) has been proven to be highly toxic to humans, but limited attention has focused on exposure levels and potential risks to mother-neonate pairs of coastal populations. This study was conducted by examining the As concentration in colostrum and umbilical cord serum collected from 106 mother-neonate pairs living on Shengsi Island, facing the Yangtze River estuary and Hangzhou Bay in China. Average concentrations of total As in colostrum and cord serum were 18.51 ± 7.00 and 19.83 ± 10.50 µg L-1. One-way ANOVA analysis showed delivered ages and source of drinking water played significant roles in influencing the maternal exposure patterns. Correlation analysis indicated a significantly positive association between As concentrations in colostrum and cord serum. Multivariable linear regression models adjusted for other confounders clarified the dose-response relationship with a coefficient value of 0.23 and a 95 % confidence interval of (0.006, 0.492); p < 0.05. The calculated daily intake of total As for neonates through breastfeeding was in the range from 0.413 to 3.65 µg kg-1 body weight, and colostrum As, especially the most toxic species, inorganic arsenic (iAs), would pose a risk to neonates.