This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

ObjectiveTo explore the clinical efficacy of Huangjin Shuangshen Jiawei （HJSSJW） granules in treating postoperative anxiety and depression after percutaneous coronary intervention （PCI） for coronary heart disease and the effects of this medicine on inflammatory cytokines. MethodNinety-four patients diagnosed with anxiety and depression after PCI were randomized into observation and control groups （47 cases） by the double-blind method. On the basis of conventional Western medical treatment， the observation group was treated with HJSSJW granules for 12 weeks， and the control group with the simulant of HJSSJW granules for 12 weeks. The two groups were compared in terms of Hamilton Anxiety and Depression Scales （HAMA-14， HAMD-24）， Pittsburgh Sleep Quality Inventory （PSQI）， Seattle Angina Score （SAQ）， TCM symptom scores， traditional Chinese medicine （TCM） symptom score and response rate， serum levels of hypersensitive-C reactive protein （hs-CPR）， tumor necrosis factor （TNF）-α， and interleukin （IL-6）， and incidence of major adverse cardiovascular events （MACEs） and adverse reactions. ResultAfter treatment， both groups showed declined scores of HAMA-14， HAMD-24， and PSQI （P<0.05， P<0.01） and the observation group had lower scores of HAMA-14， HAMD-24， and PSQI than the control group （P<0.01）. The scores of SAQ in both groups increased after treatment （P<0.01）， and the observation group had higher score of each dimension than the control group （P<0.05）. The TCM symptom scores decreased in both groups after treatment （P<0.01）， and they were lower in the observation group than in the control group （P<0.05）. The total response rate regarding TCM symptoms in the observation group was higher than that in the control group （χ²=9.225， P<0.01）. After treatment， the levels of hs-CPR， IL-6， and TNF-α became lowered in both groups （P<0.01）， and the observation group had lower levels of hs-CPR， IL-6， and TNF-α than the control group （P<0.05）. The incidence of MACEs in the observation group was lower than that in the control group during the 90 d of the follow-up period （χ²=4.242， P<0.05）. No adverse reactions associated with the use of HJSSJW granules were observed during the trial period. ConclusionHJSSJW granules can alleviate the bad mood， improve sleep， mitigate somatic symptoms， improve the quality of life， reduce inflammatory damage， and improve prognosis， being safe for clinical use in patients with postoperative anxiety and depression after PCI for coronary heart disease.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.