OBJECTIVE: To observe the effects of Tongdu Tiaoshen acupuncture (for unblocking the obstruction in the governor vessel and regulating the spirit) on depression-like behavior and the hippocampal Endophilin A1/reactive oxygen species (ROS) pathway in the chronic unpredictable mild stress (CUMS) model rats, and explore the mechanism of this therapy for depression. METHODS: Forty-eight male SD rats of SPF grade were randomly divided into a normal group (n=12) and a modeling group (n=36). In the modeling group, CUMS was performed to establish depression model. The successfully-modeled rats were randomized into a model group, a Tongdu Tiaoshen acupuncture group (referred to as the acupuncture group), and a fluoxetine group, with 12 rats in each group. In the acupuncture group, "Baihui" (GV20), "Shenting" (GV24), "Shuigou" (GV26) and "Dazhui" (GV14) were stimulated with acupuncture. This intervention measure was delivered once a day, continuously for 6 days; it was discontinued on day 7 and was completed in 28 days. In the fluoxetine group, intragastric administration was done with fluoxetine solution (2.1 mg/kg), once a day, and for 28 consecutive days. Before and after modeling, and after intervention completion, the body mass, sucrose preference rate and the total distance of movement and the boxes of horizontal crossing in the open field experiment were observed in each group. After intervention, using HE staining, the hippocampal neuron morphology was observed; using Nissl staining, the hippocampal Nissl body number was counted. The hippocampal mitochondria was observed under transmission electron microscopy. The average fluorescence intensity of ROS in hippocampal was determined using flow cytometry. With Western blot method, the protein expression of Endophilin A1, growth associated protein 43 (GAP-43), and brain-derived neurotrophic factor (BDNF) in hippocampal was detected; and with RT-qPCR method, the mRNA expression of Endophilin A1, GAP-43, and BDNF was recorded. Using the immunofluorescence, the average fluorescence intensity of Endophilin A1, GAP-43, and BDNF in hippocampal tissue was determined. RESULTS: Compared with the normal group, in the model group, the body mass, sucrose preference rate, and the total distance of movement and the boxes of horizontal crossing in the open field experiment decreased (P<0.01); the hippocampal neuronal structure was unclear, the matrix was relatively loose, and the number of Nissl body decreased (P<0.01); mitochondrial structure was disarranged, the outer membrane was ruptured, mitochondrial cristae was irregular or missed; the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue increased (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and its average fluorescence intensity decreased (P<0.01). Compared with the model group, the acupuncture group and the fluoxetine group showed the increase in body mass, sucrose preference rate, the total distance of movement and the boxes of horizontal crossing in the open field experiment (P<0.05, P<0.01); the hippocampal neuronal structure became relatively clear, the matrix was relatively dense, and the number of Nissl body was elevated (P<0.01); mitochondrial structure got normal and disarranged slightly, the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue were reduced (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and the average fluorescence intensity rose (P<0.01, P<0.05). Compared with the fluoxetine group, the acupuncture group presented the increase in the average fluorescence intensity of ROS, the protein expression and the average fluorescence intensity of Endophilin A1, the protein expression of GAP-43 and the mRNA expression of BDNF (P<0.01, P<0.05), and the decrease of the protein expression and the average fluorescence intensity of BDNF, the mRNA expression of Endophilin A1, and the average fluorescence intensity of GAP-43 (P<0.01, P<0.05). CONCLUSION Tongdu tiaoshen acupuncture alleviates depression-like behaviors in CUMS model rats and protects hippocampal neurons, which may be related to suppressing Endophilin A1/ROS signaling pathway and attenuating oxidative stress reactions.
Animals ; Male ; Hippocampus/metabolism* ; Acupuncture Therapy ; Rats, Sprague-Dawley ; Rats ; Depression/psychology* ; Humans ; Reactive Oxygen Species/metabolism* ; Disease Models, Animal ; Acupuncture Points

Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.

Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G₂ phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that β-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.
Animals ; Mice ; T-Lymphocytes, Regulatory ; Psoriasis/drug therapy* ; Arthritis, Rheumatoid ; Biological Assay ; Glucosides/pharmacology*

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies

OBJECTIVE： To screen the quality control components of Chrysanthemum morifolium based multiple component metabolism， and study its network pharmacology effect. METHODS： The water extract of C. morifolium was prepared. A total of one rats were selected， water extract of C. morifolium was perfused in jejunum segment after abdominal anesthesia； plasma sample 1 was collected by double perfusion collection. Other 3 rats were given water extract of C. morifolium intragastrically， and plasma sample 2 was collected by abdominal aorta blood collection. UPLC-MS/MS was used to analyze water extract of C. morifolium and plasma sample component， and prototype blood-entry component in water extract of C. morifolium was identified after metabolism. TCMSP and Swiss Target Prediction database were used to screen the core target of prototype blood-entry component. DAVID database was used to enrich the related pathways of core target. The quality control components were screened according to topological parameters. Cytoscape software was used to analyze pharmacological effect of quality control components of C. morifolium. RESULTS： After UPLC-MS/MS analysis， 27 compounds were identified in water extract of C. morifolium， among which there were 12 prototype blood-entry components. After network pharmacology analysis， 7 quality control components were identified， i.e. cosmosiin， apigenin-7-O-glucuronide， luteolin， tilianin， apigenin， hesperetin， acacetin. It was possible to treat cancer， cardiovascular and cerebrovascular diseases， and neurological diseases by acting on metabolic pathway， cancer related pathway， signal transduction related pathway， adipocyte lipolysis regulatory pathway， etc. CONCLUSIONS： The study screen the possible quality control components of water extract of C. morifolium. The theoretical pharmacological effect of it can be clarified through network pharmacology， which can provide a new idea for the utilization of C. morifolium.

Objective To investigate the expression of interleukin-3 receptor alpha(CD123)on bone marrow cells in acute myelocytic leukemia(AML)and its clinical significances.Methods By means of Fluorescence-activated cell sorer(FACS)and semi-quantity reverse transcripition polymerase chain reaction(RT-PCR),the expression of IL-3R?(CD123+)protein on CD34+CD38-cells and mRNA in BMMNCs of 62 AML patients of Tianjin Medical University General Hospital from March 2008 to January 2009 and 12 normal controls were detected respectively;Then the correlation between IL-3R? and the clinical stages of AML were analyzed.Results CD34+CD38-CD123+/CD34+CD38-and IL-3R? mRNA in BMMNC of 33 deno-vo or relapsed AML patients were higher than those of control group(P