Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop.

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

A novel 7-chemokine-genes predictive signature for prognosis and therapeutic response in renal clear cell carcinoma.

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevailing type of malignancies, which is affected by chemokines. Chemokines can form a local network to regulate the movement of immune cells and are essential for tumor proliferation and metastasis as well as for the interaction between tumor cells and mesenchymal cells. Establishing a chemokine genes signature to assess prognosis and therapy responsiveness in ccRCC is the goal of this effort. Methods: mRNA sequencing data and clinicopathological data on 526 individuals with ccRCC were gathered from the The Cancer Genome Atlas database for this investigation (263 training group samples and 263 validation group samples). Utilizing the LASSO algorithm in conjunction with univariate Cox analysis, the gene signature was constructed. The Gene Expression Omnibus (GEO) database provided the single cell RNA sequencing (scRNA-seq) data, and the R package "Seurat" was applied to analyze the scRNA-seq data. In addition, the enrichment scores of 28 immune cells in the tumor microenvironment (TME) were calculated using the "ssGSEA" algorithm. In order to develop possible medications for patients with high-risk ccRCC, the "pRRophetic" package is employed. Results: High-risk patients had lower overall survival in this model for predicting prognosis, which was supported by the validation cohort. In both cohorts, it served as an independent prognostic factor. Annotation of the predicted signature's biological function revealed that it was correlated with immune-related pathways, and the riskscore was positively correlated with immune cell infiltration and several immune checkpoints (ICs), including CD47, PDCD1, TIGIT, and LAG-3, while it was negatively correlated with TNFRSF14. The CXCL2, CXCL12, and CX3CL1 genes of this signature were shown to be significantly expressed in monocytes and cancer cells, according to scRNA-seq analysis. Furthermore, the high expression of CD47 in cancer cells suggested us that this could be a promising immune checkpoint. For patients who had high riskscore, we predicted 12 potential medications. Conclusion: Overall, our findings show that a putative 7-chemokine-gene signature might predict a patient's prognosis for ccRCC and reflect the disease's complicated immunological environment. Additionally, it offers suggestions on how to treat ccRCC using precision treatment and focused risk assessment.

Changes of hippocampal gray matter volume and immune related genes in dizocilpine-induced schizophrenia model rats / 中华行为医学与脑科学杂志

Objective:To investigate the changes of hippocampal gray matter volume and expression of candidate immune related genes in a rat model of schizophrenia established by repeated administration of dizocilpine(MK-801).Methods:Thirty SPF grade Sprague-Dawley male rats at postnatal day 28 were randomly divided into MK-801 medium-dose (0.25 mg/kg) group, MK-801 high-dose(0.50 mg/kg) group and normal saline (5 mL/kg) group according to random number table method, with 10 in each group.Rats were given continuous intraperitoneal administration according to grouping once a day for 14 days.Open field test, novel object recognition test and Y-maze test were used at postnatal day 60 to detect spontaneous activity, exploration ability, anxiety level, object recognition memory ability and spatial working memory of rats, respectively.At postnatal day 67, structural magnetic resonance imaging was used to detect the changes of hippocampal gray matter volume in rat.And at postnatal day 70, qRT-PCR was used to detect the expression of candidate immune-related genes in rat hippocampus.SPSS 25.0 was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparisons.Results:(1)The behavioral results showed that there were significant differences in the total movement distance, central area activity time, novel object recognition index, and spontaneous correct alternation rate among the three groups ( F=11.15, 10.11, 13.62, 11.99, all P<0.05). The total movement distances in MK-801 medium-dose group and MK-801 high-dose group ((21.44±2.17) m, (22.87±1.96)m) were higher than that in the normal saline group ((18.70±1.88) m) (both P<0.05). The activity time of the central area in the MK-801 medium-dose group and MK-801 high-dose group((3.24±1.58) s, (2.50±1.32) s) were lower than that of the normal saline group ((6.05±2.48)s) (both P<0.01). Novel object recognition indexes in the MK-801 medium-dose group and MK-801 high-dose group((56.10±3.99)%, (54.00±6.41)%) were both lower than that in the normal saline group ((65.90±5.65)%)(both P<0.01), and the rates of spontaneous correct alternation ((54.60±7.03)%, (51.60±8.84)%) in the two groups were lower than that of the normal saline group ((68.40±8.57)%) (both P<0.01). (2) The results of structural magnetic resonance imaging showed that there were significant differences in the volume of hippocampal gray matter among the three groups ( F=9.24, P<0.001). The volumes of hippocampal gray matter in MK-801 medium-dose group and MK-801 high-dose group were lower than that in normal saline group(both P<0.001). (3)By constructing protein-protein interaction network, four candidate immune related genes were screened out: neuropeptide Y (NPY), somatostatin (SST), cholecystokinin (CCK) and tachykinin 1 (TAC1). The results showed that the mRNA expression levels of NPY, SST and CCK in the hippocampus of the three groups were significantly different ( F=11.41, 10.43, 5.85, all P<0.05), but there was no statistical difference in the TAC1 mRNA expression level ( F=0.08, P>0.05). The mRNA levels of NPY, SST and CCK in the hippocampus of rats in the MK-801 high-dose group were lower than those in the normal saline group (all P<0.05). Conclusion:Both medium dose and high dose MK-801 administration can reduce the volume of hippocampal gray matter in schizophrenia model rats, but they have different effects on the expression of hippocampal immune related genes, of which high dose administration has a greater effect.

Establishment of animal models for depression in the elderly and progress on their application / 中华老年医学杂志

Geriatric depression in the elderly is becoming one of the most common psychiatric disorders affecting older people's mental and physical health.However, there is currently no systematic review on animal models for geriatric depression.Therefore, this paper analyzes and summarizes the animal models commonly used in geriatric depression studies and the application of antidepressants in geriatric depression models based on relevant national and international literature of recent years, aiming to provide insights on research approaches and considerations on study methods for geriatric depression.

Current research status of hepatitis D virus RNA detection / 临床肝胆病杂志

Hepatitis D caused by hepatitis D virus (HDV) infection is the most serious type of viral hepatitis. The prevalence rate of HDV has been seriously underestimated due to the lack of accurate HDV RNA detection methods. HDV RNA is the gold standard for the diagnosis of HDV infection and is of great significance in the diagnosis, screening, and treatment guidance of HDV. However, the multiple genotypes and strong secondary structure of HDV have led to great difficulties in HDV RNA detection. This article reviews the advances in HDV RNA detection methods and elaborates on the development from qualitative to quantitative detection methods, in order to provide new ideas for understanding the significance of HDV RNA detection and promoting the research and development of new HDV RNA detection methods.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types.

Immunotherapy with checkpoint inhibitors, such as PD-1/PD-L1 blockage, is becoming standard of practice for an increasing number of cancer types. However, the response rate is only 10%-40%. Thus, identifying biomarkers that could accurately predict the ICI-therapy response is critically important. We downloaded somatic mutation data for 46,697 patients and tumor-infiltrating immune cells levels data for 11070 patients, then combined TP53 and BRAF mutation status into a biomarker model and found that the predict ability of TP53/BRAF mutation model is more powerful than some past models. Commonly, patients with high-TMB status have better response to ICI therapy than patients with low-TMB status. However, the genotype of TP53MUTBRAFWT in high-TMB status cohort have poorer response to ICI therapy than the genotype of BRAFMUTTP53WT in low-TMB status (Median, 18 months vs 47 month). Thus, TP53/BRAF mutation model can add predictive value to TMB in identifying patients who benefited from ICI treatment, which can enable more informed treatment decisions.

Serum and urinary amino acid profiling analysis for urinary stone disease using GC-MS / 中华检验医学杂志

Objective:To analyze the serum and urinary amino acid (AA) profiles of urolithiasis patients to explore the potential biomarkers for clinical screening and early diagnosis.Methods:Case-control study. Serum and urine samples were collected from 74 urolithiasis patients (aged 20-82 years, 41 men, 33 female) in the department of urology of the First Affiliated Hospital of Fujian Medical University and 35 healthy controls (HC, aged 22-80 years old, 20 men, 15 female) from the health examination center from February 2015 to October 2017. Serum and urinary AA levels of patients and HC were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) based metabolomic strategy. The multivariate statistical analysis methods of principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) were employed for modeling. The variable importance projection (VIP) value of OPLS-DA model>1 and P<0.05 of t test were selected to screen the differential amino acid metabolites. The diagnostic capabilities of potential markers were evaluated by receiver operating characteristic (ROC) curve and binary logistic regression analysis. Results:Five AA metabolites including serine, glutamate, aspartic acid, isoleucine and glycine were found, which had statistically significant differences between the patient group and the control group ( P<0.05) and were associated with seven metabolic pathways. Serum serine, glutamate, aspartic acid, isoleucine and urine glycine and aspartic acid were combined into an integrated marker panel whose AUC value was 0.890, the sensitivity was 78.0%, and the specificity was 96.4%. Conclusion:Five amino acids in serum and urine could be used as an integrated biomarker panel for the clinical screening and early diagnosis of urolithiasis, which could provide some experimental basis for molecular urolithiasis research.

Evaluation of therapeutic markers and mechanism of Shuganjieyu capsule in treatment of depression / 中华行为医学与脑科学杂志

Objective:To compare the expression levels of candidate genes before and after Shuganjieyu capsule treatment, to analyze their correlation with depression symptoms and cognitive function, and to find and clarify the biomarkers related to the efficacy of Shuganjieyu capsule.Methods:Among 27 patients with mild to moderate depression (MMD), 24 items Hamilton depression rating scale (HAMD-24) was used to assess the severity of depression, Chinese revised Wechsler adult intelligence scale(WAIS-RC) and Chinese revised Wechsler memory scale(WMS) were used to assess cognitive function, and qRT-PCR was used to detect the expression levels of candidate genes in peripheral blood of patients with depression before and after treatment with Shuganjieyu capsule.SPSS 25.0 software was used for statistical analysis, paired t-test, non-parametric test, Spearman correlation analysis and receiver operating characteristic curve were used for data statistics. Results:The symptoms of MMD patients were relieved after Shuganjieyu capsule treatment(HAMD scores: baseline 14.00(9.75, 18.25), 8-week 4.00(2.00, 7.25), Z=-4.462, P<0.01), and the verbal intelligence quotient(VIQ) of WMS was puomoved (VIQ scores: baseline (123.00±10.24), 8-week (128.00±6.77), t=4.372, P<0.01). The level of gene expression brain derived neurotrophic factor(BDNF) (baseline 1.68(0.92, 2.63), 8-week 2.30(1.47, 4.34), Z=-2.781, P=0.005), glial cell derived neurotrophic factor(GDNF) (baseline 0.74(0.31, 1.15), 8-week 0.97(0.50, 1.71), Z=-2.159, P=0.031), 5-hydroxytryptamine receptor 2A(HTR2A) (baseline 0.60(0.39, 1.60), 8-week 0.98(0.44, 2.29), Z=-1.994, P=0.046) and glutamate ionotropic receptor AMPA type subunit 1(GRIA1) (baseline 1.19(0.66, 2.40), 8-week 1.76(0.86, 4.13), Z=-2.756, P=0.006) was up-regulated after treatment.The change rate of BDNF expression were correlated with the score of HAMD-24 ( r=-0.35, P=0.038) and performance intelligence quotient of WMS ( r=0.40, P=0.022). Conclusions:BDNF may be used as a therapeutic marker of Shuganjieyu capsule in the treatment of clinical symptoms and cognitive function of MMD patients, which is used to evaluate the efficacy of antidepressants.

circCHST15 is a novel prognostic biomarker that promotes clear cell renal cell carcinoma cell proliferation and metastasis through the miR-125a-5p/EIF4EBP1 axis.

BACKGROUND: Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC. METHODS: circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization. RESULTS: The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression. CONCLUSIONS: We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.

Metabolic module identification and biological mechanism of Xiaoyaosan for treatment of depression / 药学学报

The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.

The role and mechanism of invariant natural killer T cells in liver anti-tumor immunity / 临床肝胆病杂志

Invariant natural killer T (iNKT) cells are a T lymphocyte subset derived from the thymus and can express both natural killer cell-related receptors and T cell receptor. The iNKT cells are widely distributed in the body and are enriched in the liver, and they exhibit unique functional characteristics and can secrete cytokines and regulate the activity of other immune cells in microenvironment, so as to achieve the role of immune surveillance and disease prevention; especially in tumor microenvironment, iNKT cells can stimulate anti-tumor immune response and reverse immunosuppressive microenvironment in the liver. This article reviews the biological characteristics of iNKT cells and their special role in liver immune homeostasis, especially the anti-tumor effect and mechanism of iNKT cells.

Hypoxic stimulation leads to the changes of inflammatory factors in mucosal epithelial cells of nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the roles of hypoxic stimulation in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing the variation and differences of inflammatory factors secreted from epithelial cells of nasal polyps and normal nasal mucosa under hypoxic stimulation. Methods: Sixty-eight patients who were diagnosed with CRSwNP from June 2015 to January 2018 at China-Japan Union Hospital of Jilin University were analyzed, including 36 males and 32 females, aged (45.2±12.5) years. Nasal polyps mucosa was included in CRS-NP group and inferior turbinate mucosa was included in CRS-IT group. According to the degree of eosinophil infiltration in histopathologic results, each of these two groups was further divided into eosinophil infiltration and non-eosinophil infiltration as Eos-NP group (n=34), Non-Eos-NP group (n=34), Eos-IT group (n=20) and Non-Eos-IT group (n=20). The inferior turbinate mucosa of twenty-five patients who were diagnosed with cyst of paranasal sinus or deviation of nasal septum was classified as control group (n=25), including 14 males and 11 females, aged (42.8±10.2) years. The expression of interleukin 17A (IL-17A), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in each group was analyzed by immunohistochemical staining. After 0, 24 and 48 h hypoxic stimulation, the secretion of IL-17A, IFN-γ, TNF-α in primary nasal mucosa epithelial cells of each group was tested by enzyme-linked immune sorbent assay (ELISA) experiment; the expression of HIF-1α was tested by immunofluorescent staining and imaging and Western blot. SPSS 17.0 software and two-way ANOVA were used for statistical analysis. Results: Immunohistochemical staining showed that the expression of IL-17A and TNF-α was much higher in control group (optical density (OD) value was 0.37±0.03, 0.53±0.02, respectively) and the expression of IFN-γ and HIF-1α was much higher in Eos-IT group (OD value was 0.47±0.03, 0.39±0.02, respectively). The secretion of IL-17A and TNF-α was much lower in control group than that in other groups under normal condition. After 48 h hypoxic stimulation, the secretion of IL-17A and TNF-α was much higher in control group compared with other groups. The secretion of IFN-γ in Eos-NP group was much higher than that in control group under normal condition ((13.7±1.3) pg/ml vs (11.1±1.6) pg/ml, P<0.05). After 48 h hypoxic stimulation, there was no difference of IFN-γ between control group and Eos-NP group. The expression of HIF-1α decreased in Eos-NP group and Non-Eos-NP group while increased in CRS-IT group and control group upon prolonged exposure to hypoxia. HIF-1α was mostly located at cytoplasm of epithelial cells in control and CRS-IT group while mainly located at nucleus of epithelial cells in CRS-NP group. Conclusions: The secretion of IL-17A, TNF-α, IFN-γ and the expression of HIF-1α show significant difference between normal nasal mucosa, polyps and inferior turbinate of CRSwNP under hypoxic stimulation, presenting different subcellular localization. This illustrates the proteins above are involved in transcription and regulation of the gene responsible for the pathogenesis of CRSwNP.

Application of stable isotope-resolved metabolomics in glucose catabolism / 药学学报

With the rapid development of high sensitivity detection techniques such as nuclear magnetic resonance and mass spectrometry, stable isotope-resolved metabolomics has been widely used in elucidating the regulatory mechanism of metabolic pathways and metabolic flow analysis, and some breakthroughs have been made. In this paper the application of stable isotope-resolved metabolomics in glucose catabolic regulation, metabolic flow analysis and functional interpretation of key metabolic pathways is reviewed, providing references for the wider use and application of this technology.

The key role of mitochondrial energy metabolism disorder in the pathogenesis of depression / 药学学报

Depression is a common mental illness with mood disorders as the main clinical feature. In recent years numerous studies have shown that mitochondrial function and structure are abnormal in patients with depression, and changes in mitochondrial ultrastructure can lead to energy metabolism disorders in the body. It is suggested that 'mitochondrial energy metabolism disorder' may be the pathogenesis of depression. This paper reviews the intrinsic association of mitochondrial energy metabolism with depression and notes potential mechanisms from the standpoint of mitochondrial structure and function on the molecular level. We provide a reference for understanding the pathogenesis of depression and identifying the possible targets of antidepressant drugs.

Effect of interferon-α and thymopentin on the mRNA expression of APOBEC3A and APOBEC3B in HepG2.2.15 cells / 临床肝胆病杂志

ObjectiveTo investigate the effect of synergistic intervention of interferonα (IFNα) and thymopentin (TP5) on the mRNA expression of apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) in HepG2.2.15 cells. MethodsHepG2.2.15 cells were divided into blank control group, IFNα treatment group, TP5 treatment group, and IFNα+TP5 treatment group, and at 12, 24, 48, and 72 hours of treatment, quantitative real-time PCR was used to measure the mRNA expression of APOBEC3A and APOBEC3B in HepG2.2.15 cells. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank control group, the IFNα treatment group and the IFNα+TP5 treatment group had a significant increase in the mRNA expression of APOBEC3A at 12, 24, 48, and 72 hours of treatment (all P＜0001). Compared with the IFNα treatment group, the IFNα+TP5 treatment group had a significant increase in the mRNA expression of APOBEC3A at these four time points (all P＜0.001). TP5 treatment had no significant influence on the mRNA expression of APOBEC3A at each time point (all P＞0.05). There was no significant difference in the mRNA expression of APOBEC3B between the blank control group and the treatment groups (all P＞0.05). ConclusionIFNα combined with TP5 can significantly upregulate the mRNA expression of APOBEC3A in HepG2.2.15 cells.

Energy metabolism mechanism of Xiaoyaosan in treatment of depression based on integrative pharmacology-based research platform of traditional Chinese medicine / 中国药理学与毒理学杂志

Objective: To predict the action targets of antidepressant active ingredients of Xiaoyaosan in order to find out more about the "multi-component, multi-target and multi-pathway" mechanism. Methods: The target-disease target network of Xiaoyaosan antidepressant was constructed by using the integrative pharmacology- based research platform of traditional Chinese medicine. The key nodes were screened by network analysis method, and the pathway enrichment analysis of the key nodes was carried out on the basis of the network analysis method to explore its possible biological process in the treatment of depression. Results: Many components of Xiaoyaosan had antidepressant properties through ATPase Na+K+transporting subunit alpha 1, ATP synthase subunit alpha, beta and gamma targets, involving tricarboxylic acid cycle, carbohydrate metabolism, amino acid metabolism, serotonergic synapse and oxidative phosphorylation pathways. Conclusion: Xiaoyaosan plays an antidepressant role in regulating the energy metabolism through "the multi-component and multi-target" model.

Study on mechanism of Xiaoyao Powder antidepression based on Arrowsmith tool / 中草药

Using the literature retrieval tool Arrowsmith to explore the possible modern medical mechanisms of Xiaoyao Powder and single herb in the treatment of depression from the theoretical level. The related literature retrieval tool Arrowsmith was used to search and find the associated literature. The results were analyzed and summarized from the single drug, compound of Xiaoyao Powder, and common key terms. Correlation analysis between the composition of Xiaoyao Powder and the mechanism of antidepressant effect by Cytoscape tool. The results showed that different single drugs in Xiaoyao Powder may affect the nerve-endocrine-immune and other key pathways by regulating TLR4, TRPV1, Caspase-3, PPARG, COX-2, NRF2, PI3K, ERK1, MAPK, p38 MAPK, and other targets. Anxiety, restraint stress, spleen deficiency, learning, and memory play an antidepressant role. The main acting site of Xiaoyao Powder anti-depression is in the hippocampus. The antidepression effect of Xiaoyao Powder embodies the characteristics of multi-component, multi-target and multi-pathway of traditional Chinese medicine. Through Arrowsmith search, this study provides a scientific basis for further elucidating the mechanism of antidepression effect of Xiaoyao Powder, and provides research directions and ideas for the research of traditional Chinese medicine compound prescription.

Application of metabolomics in antidepressant pharmacological research of Xiaoyao Powder / 中草药

Metabolomics, as an important part of systematic biology, is more closely related to phenotype, and has the characteristics of integrity, objectivity, sensitivity and dynamics, which enables it to be rapidly applied and popularized in the research field of traditional Chinese medicine. In this paper, the application of metabolomics in antidepressant pharmacological research, screening of pharmacodynamic markers and development of new antidepressant drugs were summarized. Xiaoyao Powder can achieve the therapeutic effect through the rectifying effect of energy metabolism and intestinal microflora metabolism. Amino acids, sugars, and other substances may be the diagnostic markers of depression or therapeutic markers of Xiaoyao Powder. On the basis of fully exploring the scientific connotation of the antidepressant effect of Xiaoyao Powder, a new antidepressant medicine was created to provide new ideas and explore new approaches for the inheritance and development of the classic formula.

Pharmacological Mechanism of Xiaoyaosan in Treating Depression Due to Liver Stagnation and Spleen Deficiency / 中国实验方剂学杂志

Depression belongs to the category of "stagnation syndrome" in traditional Chinese medicine. There are many clinical types of depression in which liver stagnation and spleen deficiency syndrome is one of the main types. As a classic prescription for liver-soothing and spleen-strengthening, Xiaoyaosan has a definite curative effect in the treatment of depression due to liver stagnation and spleen deficiency. With fewer adverse reactions, a high safety and good patient compliance, it can be combined with western medicine to reduce the recurrence rate and adverse reactions of western medicine, and has become the focus and hotspot of research in recent years. Although many experts and scholars have conducted a lot of research on the pharmacological mechanism of Xiaoyaosan in the treatment of depression due to liver stagnation and spleen deficiency, its mechanism is still unclear. In addition, there are many types of animal models for depression due to liver stagnation and spleen deficiency but only a few systematic reports on Xiaoyaosan in treating depression of liver stagnation and spleen deficiency. Therefore, based on two classic models of chronic mild unpredictable stress depression model (CUMS) and chronic restraint stress depression model (CIS), a review was conducted on the pharmacological mechanisms of Xiaoyaosan in the treatment of depression due to liver stagnation and spleen deficiency by regulating neurotransmitter concentration, affecting the expression of neurotrophic factor, regulating hytothalamus-pitutary-adrenal(HPA)axis imbalance, improving intestinal micro-ecology and gastrointestinal function, regulating endogenous metabolite levels and immune inflammatory factor levels and improving synaptic structure and plasticity, so as to provide potential guidelines for basis study and clinical application of Xiaoyaosan in the treatment of depression due to liver stagnation and spleen deficiency.