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

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.

[摘 要] 目的：构建靶向CD38和CD138分子抗原的双靶点嵌合抗原受体基因修饰T淋巴细胞（CD38/CD138 CAR-T细胞），探讨其对多发性骨髓瘤（MM）细胞的体外杀伤作用。方法：利用CAR-T细胞技术，基于MM细胞高表达CD38和CD138抗原，分别构建靶向CD38、CD138的CD38 CAR-T与CD138 CAR-T细胞，以及同时靶向CD38与CD138的CD38/CD138 CAR-T细胞，实验分为未处理T、CD38 CAR-T、CD138 CAR-T和CD38/CD138 CAR-T细胞组。采用流式细胞术检测CAR-T细胞的表型，利用LDH释放法检测各种CAR-T细胞对MM细胞RPMI8226和U266的体外杀伤作用。结果：成功构建CD38 CAR-T、CD138 CAR-T和CD38/CD138 CAR-T细胞。CD38/CD138 CAR-T细胞倾向于向记忆表型分化，表达较高水平的增殖分子（CD25）、激活分子（CD27）和较低水平的耗竭分子（PD-1、CTLA-4、TIM-3）（均P < 0.001），而且CD38/CD138 CAR-T细胞不易于耗竭和衰老，且表达较低水平的r-H2AX、p-p53、p21和p16蛋白（均P < 0.01）。在不同效靶比条件下，CD38/CD138 CAR-T细胞较CD38 CAR-T、CD138 CAR-T细胞对RPMI8226和U266细胞具有更强的杀伤作用（均P < 0.001）。结论：靶向CD38和CD138治疗MM的CD38/CD138 CAR-T 细胞在体外具有较优表型及较强的抗肿瘤功能。

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.