Protective effect of Xixin-Ganjiang herb pair for warming the lungs to dissolve phlegm in chronic obstructive pulmonary disease rats based on integrated network pharmacology and metabolomics.

Xixin-Ganjiang herb pair (XGHP) is a classic combination for warming the lungs to dissolve phlegm and is often used to treat a variety of chronic lung diseases; it can treat the syndrome of cold phlegm obstruction of lungs. First, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to examine the composition of XGHP, and network pharmacology was used to predict its potential core targets and signaling pathways in the current study. Second, a rat model of chronic obstructive pulmonary disease (COPD) was established for assessing the anti-COPD activity of XGHP, and metabolomics was used to explore the biomarkers and metabolic pathways. Finally, the sample was validated using molecular docking and Western blotting. The integration of metabolomics and network pharmacology results identified 11 targets, 3 biomarkers, 3 pathways, and 2 metabolic pathways. Western blotting showed that XGHP effectively regulated the expression of core proteins via multiple signaling pathways (downregulation of toll-like receptor 4 [TLR4] and upregulation of serine/threonine-protein kinase 1 [p-AKT1] and nitric oxide synthase 3 [NOS3]). Molecular docking results showed that the 10 potentially active components of XGHP have good affinity with tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase 9 (MMP-9), TLR4, p-AKT1, and NOS3. Our findings suggest that XGHP may regulate glucolipid metabolism, improve energy supply, and inhibit inflammatory responses (TNF-α, IL-6, and MMP-9) via the PI3K-Akt signaling pathway and HIF-1 signaling pathway in the management of COPD.

Long-term sex-based outcomes after surgery for acute type A aortic dissection: Meta-analysis of reconstructed time-to-event data.

BACKGROUND: The influence of sex on outcomes of surgery for acute type A aortic dissection remains incompletely characterized. We sought to evaluate post-procedural survival in the follow-up of females versus males. METHODS: We carried out a systematic review with meta-analysis of Kaplan-Meier-derived time-to-event data from studies published by June 2023 in the following databases: PubMed/MEDLINE, EMBASE, Web of Science and CENTRAL/CCTR (Cochrane Controlled Trials Register). RESULTS: Twelve studies met our eligibility criteria, including 11,696 patients (3753 females; 7943 males). The mean age ranged from 41.2 to 72.6 years with low prevalence of bicuspid aortic valve (ranging from 0.0% to 12.0%) and connective tissue disorders (ranging from 0.8% to 7.3%). We found a considerable prevalence of coronary artery disease (ranging from 12.1% to 21.1%) and malperfusion (ranging from 20.0% to 46.3%). At 10 years, females undergoing surgery had a significantly higher risk of all-cause mortality compared with males (HR 1.25, 95%CI 1.14-1.38, P â€‹< â€‹0.001). CONCLUSION: In the follow-up of patients undergoing surgery for type A aortic dissection, females presented poorer overall survival in comparison with males.

Integrated network pharmacology and metabolomics analyses of the mechanism underlying the efficacy of Ma-Mu-Ran Antidiarrheal Capsules against dextran sulfate sodium-induced ulcerative colitis.

The current study utilizes a comprehensive network pharmacology and metabolomics analysis to investigate the mechanism of action of Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) for the treatment of ulcerative colitis (UC). In this study, we established a mouse model of UC using dextran sulfate sodium. Colonic tissues were collected from mice and then subjected to hematoxylin and eosin staining, as well as histopathological analysis, to assess the therapeutic effect of MMRAC. Furthermore, we assessed the mechanisms through which MMRAC combats UC by employing integrated metabolomics and network pharmacology strategies. Lastly, we validated the key targets identified through western blot and molecular docking. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape to identify eight endogenous metabolites involved in the therapeutic action of MMRAC on UC. Further comprehensive analyses were focused on four key targets and their associated core metabolites and pathways. The results of western blot and molecular docking demonstrated that MMRAC could modulate key targets and their expression levels. The cumulative results indicated that MMRAC restored intestinal function in UC, reduced inflammatory responses, and alleviated oxidative stress by influencing the methionine and cysteine metabolic pathways, as well as the urea cycle. In addition, it had an impact on arginine, proline, glutamate, aspartate, and asparagine metabolic pathways and their associated targets.

Mechanism of Shiliu Buxue Syrup for anemia using integrated metabolomics and network pharmacology.

For many years, Shiliu Buxue Syrup (SLBXS) has been used in the treatment of anemia in Xinjiang, China. However, the potential therapeutic mechanism of SLBXS in the treatment of anemia remains unclear. We qualitatively analyzed the ingredients of SLBXS and predicted the underlying mechanisms by network pharmacology. A mice model of anemia was established by subcutaneous injection of 1-Acetyl-2-phenylhydrazine (APH). Spleen metabolomics was performed to screen potential biomarkers and pathways related to anemia. Furthermore, core targets of crucial pathways were experimentally validated. Finally, molecular docking was used for predicting interactions between compositions and targets. Network pharmacology indicated that the 230 SLBXS ingredients may affect 141 target proteins to regulate the PI3K/AKT and HIF-1 signaling pathways. Metabolomics revealed that SLBXS could mediate 30 biomarkers, such as phosphoric acid, l-pyroglutamic acid, alpha-Tocopherol, 1-stearoyl-rac-glycerol, and dihydroxyacetone phosphate, to regulate drug metabolism-other enzymes, glutathione metabolism, glycolysis or gluconeogenesis, nicotinate and nicotinamide metabolism, nitrogen metabolism, and purine metabolism. Western blot indicated that SLBXS can regulate the protein expression levels of AKT1, Bcl2, Caspase3, HIF-1α, VEGF-A, and NOS2. The molecular docking revealed that most of the compositions had a good binding ability to the core targets. Based on these findings, we speculate that SLBXS treats anemia mainly by modulating the PI3K/AKT and HIF-1 pathways and glutathione and glycolytic metabolisms.

Macrovasculature and positron emission tomography (PET) standardized uptake value in patients with lung cancer.

PURPOSE: To investigate the relationship between macrovasculature features and the standardized uptake value (SUV) of positron emission tomography (PET), which is a surrogate for the metabolic activity of a lung tumor. METHODS: We retrospectively analyzed a cohort of 90 lung cancer patients who had both chest CT and PET-CT examinations before receiving cancer treatment. The SUVs in the medical reports were used. We quantified three macrovasculature features depicted on CT images (i.e., vessel number, vessel volume, and vessel tortuosity) and several tumor features (i.e., volume, maximum diameter, mean diameter, surface area, and density). Tumor size (e.g., volume) was used as a covariate to adjust for possible confounding factors. Backward stepwise multiple regression analysis was performed to develop a model for predicting PET SUV from the relevant image features. The Bonferroni correction was used for multiple comparisons. RESULTS: PET SUV was positively correlated with vessel volume (R = 0.44, p < 0.001) and vessel number (R = 0.44, p < 0.001) but not with vessel tortuosity (R = 0.124, p > 0.05). After adjusting for tumor size, PET SUV was significantly correlated with vessel tortuosity (R = 0.299, p = 0.004) and vessel number (R = 0.224, p = 0.035), but only marginally correlated with vessel volume (R = 0.187, p = 0.079). The multiple regression model showed a performance with an R-Squared of 0.391 and an adjusted R-Squared of 0.355 (p < 0.001). CONCLUSIONS: Our investigations demonstrate the potential relationship between macrovasculature and PET SUV and suggest the possibility of inferring the metabolic activity of a lung tumor from chest CT images.

Effects of acupoint catgut embedding on the postmenopausal osteoporosis patients and related mechanism.

OBJECTIVE: To study the effect and mechanism of acupoint catgut embedding on patients of postmenopausal osteoporosis (PMOP). METHODS: In this prospective study, 90 patients with PMOP who received treatment in our hospital were randomly divided into the drug treatment group (n=45) and drug treatment + catgut embedding group (n=45) according to SPSS random table method. The drug treatment group was given conventional western medicine treatment, and the drug treatment + catgut embedding group was given point embedding therapy. Bone mineral density (BMD), calcium (Ca2+), osteoprotegerin (OPG), estrogen (E2), receptor activator of nuclear factor-kB ligand (RANKL), liver and kidney function and blood lipids were detected before treatment in the two groups, and visual analogue score (VAS) and PMOP symptom score were evaluated. The above-mentioned indexes were detected again 3 months and 6 months after treatment. RESULTS: At 3 and 6 months after treatment, the BMD and the levels of Ca2+ and E2 in the two groups were increased, while the levels of OPG and RANKL were decreased, and the improvement in the drug treatment + catgut embedding group was significantly better than that in the drug treatment group (P<0.05). The symptom scores of VAS and PMOP in the drug treatment + catgut embedding group were significantly lower than those in the drug treatment group (all P<0.001). There was no significant difference in the levels of alanine aminotransferase (ALT), total bilirubin (TBil), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA) between the two groups, but the levels of total cholesterol (TC) and triglyceride (TG) in the drug treatment + catgut embedding group were significantly lower than those in the drug treatment group (all P<0.001). CONCLUSION: Acupoint catgut embedding has a good effect on PMOP, and it can increase BMO and improve the clinical symptoms of patients, which is worthy of clinical promotion.