1.Characteristic Expression of Multiple Neurotransmitters Oscillation Imbabance in Brains of 1 028 Patients with Depression
Anqi WANG ; Xuemei QING ; Yanshu PAN ; Pingfa ZHANG ; Ying ZHANG ; Jian LI ; Cheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):278-286
ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine (5-HT), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), inhibitory neurotransmitter (INH), and excitatory neurotransmitter (EXC) in the whole brain and different brain regions of depression patients by Search of Encephalo Telex (SET), providing new ideas for the study of heterogeneous etiology of depression. Methods(1) A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions: left frontal region (F3), right frontal region (F4), left central region (C3), right central region (C4), left parietal region (P3), right parietal region (P4), left occipital region (O1), right occipital region (O2), left anterior temporal region (F7), right anterior temporal region (F8), left posterior temporal region (T5), and right posterior temporal region (T6). The expression information of each neurotransmitter was compared with the normal model, and it was found that single neurotransmitter was in one of three states: increased, decreased, or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. (2) A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. (3) Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results(1) The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states (increased/decreased/normal), being normal in the majority. The decreased and increased expression of 5-HT, ACh, DA, INH, EXC, and NE in the whole brain occurred in 6% and 25%, 31% and 17%, 36% and 9%, 15% and 31%, 32% and 14%, and 22% and 22%, respectively. (2) The antagonizing pairs of neurotransmitters (EXC/INH, DA/5-HT, and ACh/NE) showed significant antagonistic relationships in the whole brain and different brain regions, with a strong negative correlation between EXC and INH (P<0.01, |r| values ranging from 0.69 to 0.76), a strong negative correlation between DA and 5-HT (P<0.01, |r| values ranging from 0.83 to 0.90), and a moderate negative correlation between ACh and NE (P<0.01, with |r| values ranging from 0.56 to 0.66). Meanwhile, non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations, with DA/NE (P<0.01, |r| values ranging from 0.38 to 0.46) and NE/EXC (P<0.01, |r| values ranging from 0.56 to 0.61) showing weak and moderate negative correlations, respectively, and DA/EXC showing a weak positive correlation (P<0.01, |r| values ranging from 0.38 to 0.47). (3) The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper, with a cumulative rate of 60.60%, including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- (9.05%), ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- (4.57%), and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- (3.31%). That is, the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%, and the patients with at least one neurotransmitter abnormality accounted for 91.95%. (4) The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues (F) ranging from 1.03 to 13.43, with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① AChP3↓/AChW↓/AChC3↓/AChF3↓/AChO1↓/AChT5↓/AChF7↓/NEP3↑/NEW↑/NEC3↑/NEF3↑/NEO1↑/NET5↑/NEF7↑ (F=13.43, whole brain), ② 5-HTO2↑/DAO2↓/5-HTP4↑/DAP4↓/5-HTW↑/DAW↓/5-HTC4↑/DAC4↓ (F=5.94), and ③ EXCF4↓/DAF4↓/NEF4↑/INHF4↑/5-HTF4↑/AChF4↓ (F=5.33). ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary, this study provides new guidance for the etiology, diagnosis, and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.
2.Characteristic Expression of Multiple Neurotransmitters Oscillation Imbabance in Brains of 1 028 Patients with Depression
Anqi WANG ; Xuemei QING ; Yanshu PAN ; Pingfa ZHANG ; Ying ZHANG ; Jian LI ; Cheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):278-286
ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine (5-HT), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), inhibitory neurotransmitter (INH), and excitatory neurotransmitter (EXC) in the whole brain and different brain regions of depression patients by Search of Encephalo Telex (SET), providing new ideas for the study of heterogeneous etiology of depression. Methods(1) A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions: left frontal region (F3), right frontal region (F4), left central region (C3), right central region (C4), left parietal region (P3), right parietal region (P4), left occipital region (O1), right occipital region (O2), left anterior temporal region (F7), right anterior temporal region (F8), left posterior temporal region (T5), and right posterior temporal region (T6). The expression information of each neurotransmitter was compared with the normal model, and it was found that single neurotransmitter was in one of three states: increased, decreased, or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. (2) A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. (3) Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results(1) The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states (increased/decreased/normal), being normal in the majority. The decreased and increased expression of 5-HT, ACh, DA, INH, EXC, and NE in the whole brain occurred in 6% and 25%, 31% and 17%, 36% and 9%, 15% and 31%, 32% and 14%, and 22% and 22%, respectively. (2) The antagonizing pairs of neurotransmitters (EXC/INH, DA/5-HT, and ACh/NE) showed significant antagonistic relationships in the whole brain and different brain regions, with a strong negative correlation between EXC and INH (P<0.01, |r| values ranging from 0.69 to 0.76), a strong negative correlation between DA and 5-HT (P<0.01, |r| values ranging from 0.83 to 0.90), and a moderate negative correlation between ACh and NE (P<0.01, with |r| values ranging from 0.56 to 0.66). Meanwhile, non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations, with DA/NE (P<0.01, |r| values ranging from 0.38 to 0.46) and NE/EXC (P<0.01, |r| values ranging from 0.56 to 0.61) showing weak and moderate negative correlations, respectively, and DA/EXC showing a weak positive correlation (P<0.01, |r| values ranging from 0.38 to 0.47). (3) The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper, with a cumulative rate of 60.60%, including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- (9.05%), ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- (4.57%), and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- (3.31%). That is, the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%, and the patients with at least one neurotransmitter abnormality accounted for 91.95%. (4) The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues (F) ranging from 1.03 to 13.43, with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① AChP3↓/AChW↓/AChC3↓/AChF3↓/AChO1↓/AChT5↓/AChF7↓/NEP3↑/NEW↑/NEC3↑/NEF3↑/NEO1↑/NET5↑/NEF7↑ (F=13.43, whole brain), ② 5-HTO2↑/DAO2↓/5-HTP4↑/DAP4↓/5-HTW↑/DAW↓/5-HTC4↑/DAC4↓ (F=5.94), and ③ EXCF4↓/DAF4↓/NEF4↑/INHF4↑/5-HTF4↑/AChF4↓ (F=5.33). ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary, this study provides new guidance for the etiology, diagnosis, and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.
3.Construction of Saccharomyces cerevisiae cell factory for efficient biosynthesis of ferruginol.
Mei-Ling JIANG ; Zhen-Jiang TIAN ; Hao TANG ; Xin-Qi SONG ; Jian WANG ; Ying MA ; Ping SU ; Guo-Wei JIA ; Ya-Ting HU ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2025;50(4):1031-1042
Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics*
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Diterpenes/metabolism*
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Metabolic Engineering
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Fermentation
;
Abietanes
4.Medicinal properties and mechanisms of p-cymene with mild and warm nature based on deficiency-cold and deficiency-heat syndrome models.
Xiao-Fang WU ; Yi LI ; Xing-Yu ZHAO ; Lin-Ze LI ; Qi ZHANG ; Yin-Ming ZHAO ; Ying-Li ZHU ; Chun WANG ; Jian-Jun ZHANG ; Lin-Yuan WANG
China Journal of Chinese Materia Medica 2025;50(8):2032-2040
This paper aims to study the effect of p-cymene on mice with deficiency-cold syndrome induced by hydrocortisone and deficiency-heat syndrome induced by dexamethasone and explore the medicinal properties and mechanism of p-cymene with mild and warm nature based on the dominant characteristics of the two-way applicable conditions of mild drugs. A total of 80 KM mice were randomly divided into blank group, deficiency-cold syndrome model group, deficiency-cold syndrome + ginseng group, and deficiency-cold syndrome + low-dose and high-dose p-cymene groups, as well as blank group, deficiency-heat syndrome model group, deficiency-heat syndrome + American ginseng group, and deficiency-heat syndrome + low-dose and high-dose p-cymene groups. Hydrocortisone and dexamethasone solution were intragastrically administered for 14 consecutive days to prepare deficiency-cold syndrome and deficiency-heat syndrome models. Except for the blank group and the model group intragastrically administered with normal saline, the other groups were intragastrically administrated with drugs for 14 days. The levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), total cholesterol(TC), triglyceride(TG), immunoglobin G(IgG), and immunoglobin M(IgM) in serum, as well as the activity of Na~+-K~+-ATPase in liver tissue were detected. The expression of transient receptor potential melastatin 8(TRPM8), transient receptor potential vanilloid 1(TRPV1), and uncoupling protein 1(UCP1) in brown adipose tissue of deficiency-cold syndrome model after intervention with p-cymene was studied. The results showed that p-cymene could effectively improve the levels of cAMP, cAMP/cGMP, TC, IgM, and IgG in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and reduce the content of cGMP. The effects on T3, T4, and TG were not statistically significant. At the same time, p-cymene could reduce the levels of cAMP, cAMP/cGMP, and T4 in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and increase the levels of cGMP, IgM, and IgG, and it had no effect on T3, TC, and TG. In addition, p-cymene could up-regulate the expression of TRPV1 and UCP1 in brown fat of mice with deficiency-cold syndrome and down-regulate the expression of TRPM8. In summary, p-cymene could significantly regulate the syndrome indexes of mice with deficiency-cold syndrome, and some indexes of mice with deficiency-heat syndrome could be improved, but the effects on lipid metabolism and energy metabolism indexes were not obvious, indicating that the regulation effect of p-cymene on deficiency-cold syndrome model was more prominent and that the medicinal properties of p-cymene were mild and warm. The regulation of TRPV1/TRPM8/UCP1 channel expression may be the molecular biological mechanism of p-cymene with mild and warm nature affecting the energy metabolism of the body.
Animals
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Cymenes
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Mice
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Disease Models, Animal
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Humans
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Cyclic AMP/metabolism*
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Monoterpenes/administration & dosage*
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Liver/metabolism*
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Cyclic GMP/metabolism*
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TRPV Cation Channels/genetics*
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Uncoupling Protein 1/genetics*
5.Mechanism of Maxiong Powder in inhibiting Epac1-Piezo2 signaling pathway in medial habenular nucleus-interpeduncular nucleus of rats with neuropathic pain.
Xin-Yuan WANG ; Zhi CHEN ; Ying LIU ; Jian SUN ; Ru-Jie LI ; Zhi-Guo WANG ; Mei-Yu ZHANG
China Journal of Chinese Materia Medica 2025;50(10):2719-2729
Central sensitization(CS) is an important factor in inducing neuropathic pain(NPP), and the association between signal transduction protein 1(Epac1) and piezoelectric type mechanosensitive ion channel component 2(Piezo2) is a new and significant pathway for initiating CS. This study whether the central analgesic effect of Maxiong Powder is achieved through the synchronized regulation of the Epac1-Piezo2 signaling pathway in the medial habenular nucleus(MHb) and interpeduncular nucleus(IPN) of the brain. Dynamic in vivo microdialysis, combined with high-performance liquid chromatography-fluorescence detection(HPLC-RFC), behavioral assessments, immunohistochemistry, Western blot, and quantitative reverse transcription PCR, were employed in rats with partial sciatic nerve injury(SNI) to investigate the distribution and expression of Epac1 and Piezo2 proteins and genes in the MHb and IPN regions, and the changes in the extracellular levels of glutamate(Glu), aspartic acid(Asp), and glycine(Gly). Compared with the sham group, rats in the SNI group showed significantly reduced analgesic activity, a significant increase in cold pain sensitivity scores, and elevated Glu levels in the MHb and IPN regions. Additionally, the number of Piezo2-positive cells in these regions, as well as the expression levels of Epac1 and Piezo2 proteins and genes, were significantly increased. Compared with the SNI group, after Maxiong Powder administration, the analgesic activity in rats significantly increased, and cold pain sensitivity scores were significantly reduced. Maxiong Powder also significantly decreased the Glu content in the MHb and IPN regions and the Gly content in the MHb region, while significantly increasing the Asp content in both regions. Furthermore, Maxiong Powder significantly reduced the number of Piezo2-positive cells and lowered the protein and gene expression levels of Epac1 and Piezo2 in both brain regions. The central analgesic effect of Maxiong Powder may be related to its inhibition of Glu and Gly release in the extracellular fluid of the MHb and IPN regions, the increase of Asp levels in these regions, and the regulation of the Epac1-Piezo2 pathway through the reduction of Epac1 and Piezo2 protein and gene expression. These results provide partial scientific evidence for the clinical analgesic efficacy of Maxiong Powder and offer new ideas and approaches for the clinical treatment of NPP.
Animals
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Neuralgia/genetics*
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Rats
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Signal Transduction/drug effects*
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Male
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Rats, Sprague-Dawley
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Guanine Nucleotide Exchange Factors/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Habenula/drug effects*
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Ion Channels/genetics*
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Humans
6.Investigation of therapeutic effects and mechanisms of Shenqi Buqi Granules on patients with chronic heart failure of Qi deficiency based on proteomics.
Zhi-Bo WANG ; Ying LI ; Lan MIAO ; Jun-Guo REN ; Jian-Xun LIU
China Journal of Chinese Materia Medica 2025;50(11):3168-3179
This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P<0.05) and PPP1CA(r=0.62, P<0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.
Humans
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Drugs, Chinese Herbal/therapeutic use*
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Heart Failure/metabolism*
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Male
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Female
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Proteomics
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Middle Aged
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Qi
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Aged
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Protein Interaction Maps/drug effects*
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Adult
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Chronic Disease
7.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
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Male
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Rats
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Nucleus Accumbens/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Depression/complications*
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Membrane Glycoproteins/genetics*
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Rats, Sprague-Dawley
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Sleep Initiation and Maintenance Disorders/complications*
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Neurons/metabolism*
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Receptors, Immunologic/genetics*
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Signal Transduction/drug effects*
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Synapses/metabolism*
8.Protective mechanism of Chaihu Shugan San against CORT-induced damage in PC12 cells based on mitochondrial dynamics.
Ling-Yuan ZHANG ; Qi-Qi ZHENG ; Jia-Li SHI ; Pei-Fang WANG ; Jia-Li LU ; Jian-Ying SHEN
China Journal of Chinese Materia Medica 2025;50(16):4546-4554
In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals
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PC12 Cells
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Rats
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Mitochondrial Dynamics/drug effects*
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Mitochondria/metabolism*
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Corticosterone/adverse effects*
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Membrane Potential, Mitochondrial/drug effects*
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Drugs, Chinese Herbal/pharmacology*
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Protective Agents/pharmacology*
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Cell Survival/drug effects*
9.Comparison of two transforaminal endoscopic techniques for recurrent L5S1 lumbar disc herniation with high iliac crest.
Yue-Hong GUAN ; Jian WU ; Li-Jun WANG ; Bin XU ; Jian TANG ; Ying ZHANG ; Ying-Qi HE
China Journal of Orthopaedics and Traumatology 2025;38(11):1100-1105
OBJECTIVE:
To explore the clinical efficacy of conventional transforaminal endoscopic technique and I See transforaminal endoscopic technique in the treatment of recurrent L5S1 lumbar disc herniation with high iliac crest.
METHODS:
A total of 36 patients with recurrent L5S1 lumbar disc herniation with high iliac crest after posterior small-incision discectomy, admitted from May 2016 to May 2023, were selected. They were divided into the conventional transforaminal endoscopy group and the I See transforaminal endoscopy group according to the different transforaminal endoscopic techniques adopted, and all patients in both groups underwent lateral transforaminal spinal canal decompression and discectomy. There were 18 patients in the conventional transforaminal endoscopy group, including 11 males and 7 females, with an age of (52.24±6.68) years;the I See transforaminal endoscopy group also had 18 patients, including 12 males and 6 females, with an age of (50.75±7.79) years. The perioperative indicators (operation time, number of intraoperative radiographs, and length of hospital stay) were compared between two groups. The clinical efficacy was evaluated using the visual analogue scale(VAS) for pain, the Japanese Orthopaedic Association(JOA) low back pain score, and the modified MacNab criteria before and after surgery.
RESULTS:
All patients achieved gradeⅠincision healing, with no infection cases. The operation time of the I See group was (64.25±16.67) minutes, which was significantly shorter than that of the conventional transforaminal endoscopy group (89.11±17.24) minutes, and the difference was statistically significant(P<0.05). The number of intraoperative radiographs in the I See group was (5.20±2.29) times, which was significantly less than that in the conventional transforaminal endoscopy group(19.16±3.68) times, and the difference was statistically significant(P<0.05). The VAS and total JOA scores of both groups at the 3rd day, the 3rd month after surgery, and the last follow-up were significantly lower than those before surgery, with statistically significant differences(P<0.05);however, there were no statistically significant differences in VAS and total JOA scores between two groups at the 3rd day, the 3rd month after surgery, and the last follow-up (P>0.05). According to the modified MacNab criteria for efficacy evaluation:in the conventional transforaminal endoscopy group, 14 cases were excellent and 4 cases were good;in the I See transforaminal endoscopy group, 15 cases were excellent and 3 cases were good;there was no statistically significant difference in efficacy between two groups(Z=0.177, P=0.674).
CONCLUSION
Both transforaminal endoscopic techniques have good clinical effects in the treatment of recurrent L5S1 lumbar disc herniation with high iliac crest, resulting in significant improvement of postoperative symptoms, and they are safe, reliable, and minimally invasive surgical methods. Compared with the conventional transforaminal endoscopy, the I See transforaminal endoscopic technique has shorter operation time and fewer intraoperative radiographs, so it is generally the first choice.
Humans
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Male
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Female
;
Intervertebral Disc Displacement/surgery*
;
Endoscopy/methods*
;
Middle Aged
;
Lumbar Vertebrae/surgery*
;
Ilium/surgery*
;
Adult
;
Diskectomy/methods*
10.Micronucleus counts correlating with male infertility: a clinical analysis of chromosomal abnormalities and reproductive parameters.
Shun-Han ZHANG ; Ying-Jun XIE ; Wen-Jun QIU ; Qian-Ying PAN ; Li-Hao CHEN ; Jian-Feng WU ; Si-Qi HUANG ; Ding WANG ; Xiao-Fang SUN
Asian Journal of Andrology 2025;27(4):537-542
Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans
;
Male
;
Infertility, Male/genetics*
;
Adult
;
Micronucleus Tests
;
Semen Analysis
;
Oligospermia/genetics*
;
Azoospermia/genetics*
;
Chromosome Aberrations
;
Sperm Count
;
Micronuclei, Chromosome-Defective
;
Middle Aged

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