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1.
Journal of Experimental Hematology ; (6): 1093-1099, 2023.
Article in Chinese | WPRIM | ID: wpr-1009966

ABSTRACT

OBJECTIVE@#To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism.@*METHODS@#MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot.@*RESULTS@#RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV.@*CONCLUSION@#RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.


Subject(s)
Humans , Resveratrol/pharmacology , Multiple Myeloma/metabolism , Cell Proliferation , Cell Line, Tumor , Apoptosis , MicroRNAs/genetics
2.
Journal of Experimental Hematology ; (6): 832-835, 2022.
Article in Chinese | WPRIM | ID: wpr-939696

ABSTRACT

OBJECTIVE@#To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP).@*METHODS@#Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed.@*RESULTS@#The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment.@*CONCLUSION@#RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Glucocorticoids/therapeutic use , Platelet Count , Platelet Transfusion , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Recombinant Proteins/therapeutic use , Thrombopoietin/therapeutic use
3.
Acta Pharmaceutica Sinica ; (12): 2445-2452, 2022.
Article in Chinese | WPRIM | ID: wpr-937059

ABSTRACT

The combination of Shuanghuanglian injection (SHLI) and ciprofloxacin injection (CIPI) is frequently prescribed in clinical practice, but the basis for the combination is weak. In this study, isothermal titration calorimetry and ultraviolet-visible absorption spectrometry were applied to identify the molecular interactions of SHLI and its main components, chlorogenic acid and neochlorogenic acid with CIPI. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and cold-spray ionization mass spectrometry were performed to confirm that this molecular interaction was related to the formation of self-assembled supramolecular systems induced by chlorogenic acid and neochlorogenic acid with CIPI through weak intermolecular bonds. The antibacterial activity toward Pseudomonas aeruginosa (P. aeruginosa) was evaluated via molecular interactions, and the inhibitory ability of SHLI, chlorogenic acid and neochlorogenic acid against P. aeruginosa was significantly reduced after interaction with CIPI. A molecular docking study demonstrated that the reduced antibacterial ability was closely related to the competitive binding of drug molecules to the same binding site of the DNA gyrase B (GyrB) subunit of P. aeruginosa. The present study uncovered the intermolecular interactions of SHLI and its main components chlorogenic acid and neochlorogenic acid with CIPI from the perspective of molecular self-assembly and contribute to the reduction of its antibacterial ability, providing a basis for the clinical combination of SHLI and CIPI.

4.
Acta Pharmaceutica Sinica ; (12): 1471-1476, 2022.
Article in Chinese | WPRIM | ID: wpr-924753

ABSTRACT

The joint application of traditional Chinese medicine injection containing chlorogenic acid (CA) and cefotaxime sodium (CS) is sometimes appeared in clinical practice, but the scientific basis of drug molecular compatibility is still weak. This study proposes a sequential analysis strategy based on isothermal titration calorimetry (ITC), cold-spray ionization mass spectrometry (CSI-MS) and antibacterial activity test to evaluate the molecular interactions between CA and CS. The results of ITC experiments showed that the Gibbs free energy ΔG < 0 and it was driven by enthalpy change when CA titrated CS, suggesting CA could spontaneously chemically react with CS. Subsequently, the parent ions (m/z 808.143 5) of binding molecular of CA and CS was detected by CSI-MS, indicating CA could chemically bond with CS. Furtherly, the antibacterial experiments found the antibacterial ability of CS against Klebsiella pneumonia was significantly reduced (P < 0.01) by CA in mixed solution. Finally, molecular docking technology showed CA and CS have a common target of penicillin binding protein 3 (PBP3), suggesting that the phenomenon of CA reduced the antibacterial ability of CS may be related to the competitive binding of two components with PBP3. Our studies have shown that CA could spontaneously chemically bond to CS and reduced its antibacterial ability, providing scientific data for molecular interaction evaluation of CA and CS.

5.
China Journal of Chinese Materia Medica ; (24): 5341-5350, 2021.
Article in Chinese | WPRIM | ID: wpr-921681

ABSTRACT

The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic β cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic β cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic β cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic β cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, β-carotene and β-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic β cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic β cell dysfunction.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Insulin-Secreting Cells , Medicine, Chinese Traditional , Molecular Docking Simulation , Tablets , Technology
6.
Acta Pharmaceutica Sinica ; (12): 906-912, 2021.
Article in Chinese | WPRIM | ID: wpr-886975

ABSTRACT

Depression is one of the diseases with the highest disability rate in the world. A large number of studies have shown that the intake of unsaturated fatty acids can deal with depression while chronic overconsumption of saturated fatty acids is a risk factor for depression. It was suggested that the mechanism of saturated fatty acids inducing depression is related to the following four aspects: regulating the function which links to depression in whole brain and specific brain regions, including the hippocampus, the hypothalamic-pituitary-adrenal axis, the striatum, and the prefrontal cortex; stimulating the secretion of inflammatory factors; affecting the balance and function of metabolic regulatory hormones, including leptin, adiponectin, glucocorticoid, and insulin; inducing the disturbance of intestinal flora. This article reviews the relationship between dietary fatty acids and depression, and the possible mechanisms by which saturated fatty acids induce depression from the four aspects mentioned above.

7.
China Journal of Chinese Materia Medica ; (24): 2356-2362, 2021.
Article in Chinese | WPRIM | ID: wpr-879198

ABSTRACT

Drug combination is a common clinical phenomenon. However, the scientific implementation of drug combination is li-mited by the weak rational evaluation that reflects its clinical characteristics. In order to break through the limitations of existing evaluation tools, examining drug-to-drug and drug-to-target action characteristics is proposed from the physical, chemical and biological perspectives, combining clinical multicenter case resources, domestic and international drug interaction public facilities with the aim of discovering the common rules of drug combination. Machine learning technology is employed to build a system for evaluating and predicting the rationality of clinical drug combinations based on "drug characteristics-repository information-artificial intelligence" strategy, which will be debugged and validated in multi-center clinical practice, with a view to providing new ideas and technical references for the safety and efficacy of clinical drug use.


Subject(s)
Artificial Intelligence , Drug Combinations , Machine Learning , Technology
8.
China Journal of Chinese Materia Medica ; (24): 2594-2600, 2021.
Article in Chinese | WPRIM | ID: wpr-879165

ABSTRACT

To explore the drug use rules of traditional Chinese medicine(TCM) in the treatment of ulcerative colitis, and to provide some references for clinical treatment. The full-text search of "ulcerative colitis+TCM" was conducted based on CNKI. The literatures published from 2000 to 2020 were selected, and the clinical prescriptions for ulcerative colitis were selected according to the inclusion and exclusion criteria. The statistical processing and association rule analysis were carried out with use of Excel 2013, Clementine 12.0 and IBM SPSS Statistics 25.0 statistical software. A total of 177 prescriptions were obtained after retrieval of 3 432 relevant literatures, including 93 oral prescriptions and 84 enema prescriptions. Among them, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Coptidis Rhizoma, Aucklandiae Radix and Paeoniae Radix Alba were the most frequently used drugs in oral administration, with the functions of tonifying, heat clearing and Qi regulating. The drugs with high frequency in enema included Bletillae Rhizoma, Coptidis Rhizoma, Sanguisorbae Radix, Phellodendri Chinensis Cortex and Sophorae Flavescentis Radix, with the functions of heat clearing, blood stopping and tonifying. Both oral and enema means of drugs were mainly of warm, cold and slightly cold properties, and bitter and sweet flavors, involving spleen, stomach, lung and large intestine. In cluster analysis, oral and enema drugs were divi-ded into 5 groups. Accordingly, in the treatment of ulcerative colitis, tonifying medicine, heat clearing medicine and Qi regulating medicine are often used for oral administration and heat clearing medicine, hemostatic medicine and tonifying medicine are often used for enema administration. On this basis, they are combined with diuretic drugs and astringent drugs respectively.


Subject(s)
Humans , Colitis, Ulcerative/drug therapy , Data Mining , Drugs, Chinese Herbal , Medicine, Chinese Traditional
9.
Chinese Journal of Gastrointestinal Surgery ; (12): 626-632, 2021.
Article in Chinese | WPRIM | ID: wpr-942935

ABSTRACT

Objective: Due to its various anatomical variations and numerous branches, the gastrocolic vein trunk (Henle trunk) is the most common site to develop bleeding and other complications in laparoscopic right hemicolectomy for colon cancer. This study aims to investigate the role of ileocolic vein (ICV) joining with Henle trunk, a rare anatomical variation. Methods: A rare case whose ICV was newly found to involve in the formation of Henle trunk during laparoscopic resection of right hemicolon cancer was reported as right gastroepiploic vein+ right colic vein+superior right colic vein+ICV. This anatomical variation was confirmed by multi-slice spiral CT coronal two-dimensional reconstruction of right hemicolon angiography. The literatures about ICV participating in formation of Henle trunk were systematically searched from PubMed, The Cochran Library, CNKI net and Wanfang database, and the occurrence probability and composition of its anatomical variation were analyzed. Results: This was a 47-year-old female patient who underwent laparoscopic right hemicolectomy. When the vessels were dissected during operation, it was found that ICV did not accompany the ileocolic artery, but directly flowed into Henle trunk. Two-dimensional reconstructed CT images of right hemicolon vessels showed that the composition of Henle trunk was rarely varied, which was composed of right gastroepiploic vein, right colonic vein, superior right colonic vein and ICV. Five literatures were enrolled from literature retrieval. A total of 12 cases with ICV participating in the construction of Henle trunk were reported, with a probability of 0.27%-6.31% and 6 forms of the formation of Henle trunk. In this case, Henle trunk was made up of right gastroepiploic vein, right colonic vein, upper right colonic vein and ICV, which was reported for the first time. Conclusions: ICV involving in Henle trunk is a rare vascular variation, and this type of variation should be fully recognized. Careful dissection during operation is necessary to prevent intraoperative bleeding caused by improper operation.


Subject(s)
Female , Humans , Middle Aged , Anatomic Variation , Colectomy , Colonic Neoplasms/surgery , Laparoscopy , Mesenteric Veins
10.
Journal of Acupuncture and Tuina Science ; (6): 359-366, 2020.
Article in Chinese | WPRIM | ID: wpr-872423

ABSTRACT

Objective: To observe the clinical efficacy of mind-refreshing and balance-restoring needling method combined with Frenkel exercises in treating ataxia after cerebral stroke. Methods: The recruited 120 patients were randomized into an observation group and a control group, with 60 cases in each group. The control group was intervened by mind-refreshing and balance-restoring needling method, while the observation group was given additional lower-limb Frenkel exercises. Before and after treatment and at the follow-up, the ataxic lower-limb function was scored using Berg balance scale (BBS) and international cooperative ataxia rating scale (ICARS), and Barthel index (BI) was adopted to score the activities of daily living (ADL). Results: After treatment, the markedly effective rate was 70.2% and the total effective rate was 96.5% in the observation group, versus 39.7% and 87.9% in the control group, and the differences in the markedly effective rate and the total effective rate were statistically significant (P<0.01, P<0.05). The intra-group comparisons showed that the BBS, ICARS and BI scores after treatment and at the follow-up were significantly different from those before treatment in both groups (all P<0.01).There were significant differences in the BBS score between the two groups after treatment and at the follow-up (P<0.05, P<0.01); the between-group differences in the ICARS and BI scores were statistically insignificant after treatment (both P>0.05), while the between-group differences in the ICARS and BI scores were statistically significant at the follow-up (both P<0.05). The interaction effects between the scoring time of BBS and BI and the group factor were statistically significant (P<0.01, P<0.05). Conclusion: Mind-refreshing and balance-restoring needling can effectively improve the lower-limb ataxic symptoms and ADL after stroke; when combined with Fenkel exercises, this needling method can produce more significant efficacy.

11.
Chinese Journal of Hematology ; (12): 192-197, 2020.
Article in Chinese | WPRIM | ID: wpr-1012168

ABSTRACT

Objective: To construct a new CD123- specific chimeric antigen receptor in order to provide a foundation for immunotherapy of CD123 positive leukemia. Methods: A hybridoma strain (6E11) capable of stably secreting CD123 antibody was obtained by a monoclonal screening technique, and the hybridoma cells were expanded and injected intraperitoneally to the pretreated Balb/c mice. Ascites was collected and purified to obtain the monoclonal antibody (mAb) . The affinity and specificity of 6E11 mAb were measured. The variable regions of the heavy and light chains of the 6E11 mAb were cloned by RT-PCR from the 6E11 mouse hybridoma. We generated a new CD123 specific chimeric antigen receptor with a scFv fragment derived from 6E11 antibody, designated as 6E11 CAR. T cells were transduced with lentiviral supernatant from 293T cells transfected with 6E11 CAR plasmid to generate 6E11 CAR-T cells. The specific cytotoxicity of 6E11 CAR-T against CD123(+) acute myeloid leukemia (AML) cell lines and primary AML cells in vitro were evaluated by co-culture experiments, degranulation experiments and cytokine releasing assay. Results: ① A hybridoma cell line 6E11 stably secreting anti-human CD123 antibody was developed and its variable region sequences were obtained. ② The 6E11 mAb has high affinity for CD123 protein (Kd value: 2.1 nmol/L) . The 6E11 mAb specifically recognizes CD123(+) cell line THP-1 cells and does not respond to CD123(-) cell line Jurkat cells. ③ 6E11 CAR-T cells were successfully generated with a CAR expression rate higher than 60%. ④ 6E11 CAR-T cells could specifically kill CD123(+) MV4-11 cell line but had no killing effect on the CD123(-) K562 cell line. Compared with vector-T cells, 6E11 CAR-T cells have higher killing rate to MV4-11 cells[ (98.60±1.20) %vs (20.28±6.74) %, P<0.001]. ⑤ MV4-11 cells activated 6E11 CAR-T cells significantly but not Vector-T cells[ (26.33±3.30) %vs (1.17±0.06) %, P<0.001]. ⑥ 6E11 CAR-T cells released more cytokines than vector-T cells when co-cultured with MV4-11[IL-2: (92.90±1.51) pg/ml vs (6.05±3.41) pg/ml, P<0.001; TNF-α: (1 407.20±91.95) pg/ml vs (7.86±0.85) pg/ml, P<0.001; IFN-γ: (5 614.60±170.17) pg/ml vs (8.42±2.70) pg/ml, P<0.001]. The IFN-γ, IL-2 and TNF-α in the 6E11 CAR-T group were similar to those in the Vector-T group when co-cultured with K562. ⑦ 6E11 CAR-T cells could be activated by bone marrow mononuclear cells (BMMNC) derived from CD123(+) AML patients and effectively kill these BMMNC cells from CD123(+) AML patients. Conclusion: 6E11 hybridoma cell line can stably secrete highly specific monoclonal antibodies against human CD123, which can be used to detect the expression of human CD123. It can also be used to target human CD123 protein in tumor immunotherapy. CD123 CAR-T cells with 6E11 Ig variable region sequence have specific anti-leukemic activity in vitro, which may provide a new option for further clinical research of AML.


Subject(s)
Animals , Humans , Mice , Cell Line, Tumor , Interleukin-3 Receptor alpha Subunit , Leukemia, Myeloid, Acute , Receptors, Chimeric Antigen , Single-Chain Antibodies
12.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 64-68, 2020.
Article in Chinese | WPRIM | ID: wpr-843921

ABSTRACT

Objective: To investigate the expression of transcription factor SOX12 in oral squamous cell carcinoma (OSCC) by bioinformatics analysis and to clarify the connection between expression of SOX12 and clinicopathological features of OSCC, so as to elucidate the early diagnosis and prognostic significance of OSCC by SOX12. Methods:This study used the GEPIA database in conjunction with the TCGA database to analyze the expression level of SOX12 in OSCC tissues and then verify it by qRT-PCR in vitro. The LinkedOmics database was used to describe the correlation between SOX12 expression and clinical pathological parameters of OSCC and its impact on prognosis. The location of SOX12 in signal transduction and its upstream and downstream genes related to it were analyzed by the String-DB database. Results: SOX12 was highly expressed in OSCC and positively correlated with OSCC pathological grade, T stage, and N stage. The results of TCGA showed that high SOX12 mRNA expression was associated with overall survival in OSCC. The proteins interacting with SOX12 included POU3F1, POU3F2, POU3F3, MYT1L, and NRSN2, which were mainly involved in the differentiation and development of neurons. Conclusion: The TCGA database analysis found that SOX12 is highly expressed in OSCC and is associated with multiple pathological indicators of OSCC.

13.
Acta Pharmaceutica Sinica ; (12): 384-391, 2020.
Article in Chinese | WPRIM | ID: wpr-815831

ABSTRACT

Depression, a chronic syndrome with low mood, pessimism, cognitive and sleep disorders, is characterized by high incidence, high suicide rate, low consultation and treatment rate. 40%-50% of the risk of depression comes from genes, so studying on gene abnormalities serves as an important part of the research in the internal causes of depression, among which the receptor gene abnormalities are crucial factors. The study of potential receptor gene loci is expected to be new target for the treatment of depression in the future, which can provide theoretical basis for the early diagnosis, prevention and treatment of depression.

14.
Acta Pharmaceutica Sinica ; (12): 2204-2208, 2019.
Article in Chinese | WPRIM | ID: wpr-780328

ABSTRACT

Ginseng is a traditional Chinese medicine known as the "king of herbs" since ancient time in China. It was found in animal experiments that total saponins, ginsenoside monomers or glycosides from ginseng extraction all showed antidepressant effects in chronic unpredictable stress, corticosterone or lipopolysaccharide induced depression models. Taking ginsenosides as the focus, we reviewed the antidepressive mechanisms from the perspectives of various hypotheses, such as regulations of hypothalamic-pituitary-adrenal axis, monoamine neurotransmitter and neuroplasticity related to the pathogenesis of depression. The mechanism, target and pharmacodynamic targets of ginsenosides for anti-depression were summarized, in order to provide references for multi-targets and multi-level development of new anti-depression drugs, and improvement of diagnosis and treatment of depression from the perspective of traditional Chinese medicine and natural products.

15.
Chinese Acupuncture & Moxibustion ; (12): 936-939, 2019.
Article in Chinese | WPRIM | ID: wpr-776237

ABSTRACT

OBJECTIVE@#To compared the therapeutic effect between filiform fire needle assisted 308 nm excimer laser and simple 308 nm excimer laser on vitiligo of different parts.@*METHODS@#Target lesions of 134 patients were divided into an observation group and a control group according to the principle of self-controlled, 201 pieces in each one. In the observation group, filiform fire needle was performed at target lesions. Then target lesions both of the two groups were irradiated with 308 nm excimer laser at the same time. Once every 2 weeks, totally 10 treatments were required. The effective rate and effective rate, color recovery rate and responding time of different parts in the two groups were evaluated 2 weeks after treatment.@*RESULTS@#The effective rate in the observation group was 82.59% (166/201), which was higher than 68.16% (137/201) in the control group (<0.01). The effective rate of face-neck, trunk, limbs and hand-foot were 90.32%, 81.63%, 81.48% and 58.62% respectively in the observation group, which were higher than 82.80%, 69.39%, 51.85% and 31.03% in the control group (<0.01, <0.05). The color recovery rate of different parts in the observation group was higher than the control group, and the effect was faster in the observation group (<0.01, <0.05).@*CONCLUSION@#Filiform fire needle as an adjunctive therapy, combined with 308 nm excimer laser are more effective than simple 308 nm excimer laser for vitiligo of different parts. Combination therapy has a shorter responding time, the face-neck has the best effect and hand-foot has poor effect.


Subject(s)
Humans , Combined Modality Therapy , Lasers, Excimer , Neck , Treatment Outcome , Vitiligo , Therapeutics
16.
Acta Pharmaceutica Sinica ; (12): 1645-1651, 2018.
Article in Chinese | WPRIM | ID: wpr-780043

ABSTRACT

In this article, we exogenously administered glucocorticoids to rats, observed changes in the structure and function of gap junctions in the prefrontal cortex (PFC) and studied the effects of glucocorticoid receptor (GR) inhibitor mifepristone on these changes. Subcutaneous injection of corticosterone (CORT) was used to increase glucocorticoid levels in rats, intragastric administration of mifepristone antagonist GR. Sucrose preference test was conducted to evaluate anhedonia. Dye transfer assay and electron microscopy were used to analyze the function and ultrastructural changes of gap junctions in astrocytes of PFC. Immunofluorescence was used to detect the expression of connexin 43 (Cx43). Animals exposed to CORT showed behavioral deficits in sucrose preference test, exhibited significant decreases in diffusion of gap junction channel-permeable dye and abnormal gap junctional ultrastructure, as well as reductions in Cx43 puncta density in the PFC. The behavioral and cellular alterations induced by CORT were reversed or blocked by treatment with the GR antagonist mifepristone. The results suggest that mifepristone can improve the gap junction function and structural damage of astrocytes in the PFC of depressive rats induced by CORT. In conclusion, the activation of the GR receptor may contribute to gap junction dysfunction in the PFC.

17.
Chinese Journal of Pharmacology and Toxicology ; (6): 331-331, 2018.
Article in Chinese | WPRIM | ID: wpr-705365

ABSTRACT

Depression is a devastating mental disorder and major depressive disorder (MDD) that afflicts 16% of the global population at some point in their lives. Currently available classical antide-pressants (SSRIs, SNRIs, TCAs and MOIs), require a minimum of 2–4 weeks of continuous treat-ment to elicit therapeutic relief in depressed patients and are associated with high rates of non-respon-siveness, and limited duration of efficacy. Therefore, faster-acting antidepressant therapies are need-ed,particularly for patients at risk for suicide for current therapies for depression.Although the molecu-lar mechanisms underlying the pathogenesis of depression are still largely unclear, previous studies have suggested that modulators of mammalian target of rapamycin complex 1 (mTORC1) signaling may have beneficial neuroprotective and antidepressant effects. Here, we review recent advances in understanding mTORC1 signaling in depression and potential therapeutic strategies resulting from modulation of the mTORC1 signaling network. We also highlight recent studies considered to support mTORC1 signaling modulation as a rapid-acting antidepressant therapy (e.g. ketamine, scopolamine, GLYX-13, (2R,6R)-HNK, Ro-256891 etc.) and discuss future research directions. Studies on prospec-tive next-generation rapid-acting antidepressant therapies should focus on developing more selective glutamate receptors(e.g.α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs) agonists or activators)that activate the mTORC1 signaling pathway free of ketamine's adverse effects.

18.
Acta Pharmaceutica Sinica ; (12): 1410-1415, 2017.
Article in Chinese | WPRIM | ID: wpr-779742

ABSTRACT

The study was designed to explore the effects and the underlying mechanism of ginsenoside Rg1 on corticosterone (CORT)-induced astrocytes injury. The primary hippocampal and prefrontal cortical astrocytes from rats were cultured and purified. CORT was used to stimulate stress condition. Western blot was used to detect the effects of ginsenoside Rg1 on the phosphorylation of Cx43. Cell Counting Kit (CCK8) was used to detect the effects of ginsenoside Rg1 on astrocytes viability. The roles of ginsenoside Rg1 was reversed by protein kinase inhibitors in the change of astrocytes morphology. Our results showed that ginsenoside Rg1 reversed the phosphorylation of Cx43 induced by CORT; ginsenoside Rg1 significantly upregulated the cell viability of astrocytes against CORT; the role of ginsenoside Rg1 was obviously inhibited by Src protein kinase inhibitors PP2 and Akt protein kinase inhibitors BAY1125976 in prefrontal cortical astrocytes; in hippocampal astrocytes, Src protein kinase inhibitor PP2, p38 protein kinase inhibitor SB203580, Akt protein kinase inhibitor BAY1125976 significantly inhibited the cell protective effects of ginsenoside Rg1. In conclusion, ginsenoside Rg1 improved the activity of Cx43 gap junctions in astrocytes exposed to CORT; ginsenoside Rg1 protected astrocytes against that CORT activated the Src, p38 and Akt signaling pathways, and the mechanism was different in prefrontal cortical and hippocampal astrocytes.

19.
International Eye Science ; (12): 702-705, 2017.
Article in Chinese | WPRIM | ID: wpr-731364

ABSTRACT

@#AIM: To investigate the clinical effect of Qi Ming granule combined with calcium dobesilate in treatment of non-proliferative diabetic retinopathy(NPDR).<p>METHODS: Totally 94 patients with I~III stage NPDR in our hospital from January 2014 to May 2016 were collected and randomly divided into control group and observation group, all were unilateral, with 47 eyes in each group. The two groups were given control of blood glucose, diet and exercise therapy and other conventional treatment. The control group were treated with conventional western medicine calcium dobesilate treatment, 0.5g,3 times per day, the observation group combined with Qi Ming granule treatment based on control group treatment. Both groups were treated for 3mo. Two groups were observed before and after treatment for visual sensitivity and changes of serum cytokines \〖vascular endothelial growth factor(VEGF)and insulin-like growth factor-1(IGF-1), pigment epithelium derived factor(PEDG)\〗. Therapeutic effect and safety of the two groups were comprehensively evaluated and compared. <p>RESULTS: The average sensitivity of the observation group after treatment was lower than that before treatment and the control group after treatment, the difference were statistically significant(<i>P</i><0.05).The VEGF,IGF-1,PEDG of observation group after treatment, were significantly improved compared with the control group, the difference were statistically significant(<i>P</i><0.05). There were no obvious adverse reactions in the two groups, the total effective rate was 89% in the observation group, which was higher compared with the control group 72%, and the difference was statistically significant(<i>P</i><0.05). <p>CONCLUSION: Qi Ming granule combined with western medicine in the treatment of DR can effectively improve the function of the retina and ease the progress of the disease, and the safety is good, the clinical treatment effect is remarkable.

20.
Chinese Journal of Contemporary Pediatrics ; (12): 589-593, 2016.
Article in Chinese | WPRIM | ID: wpr-261185

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the characteristics of attention in school-age children with mild autism spectrum disorder (ASD), and to provide a basis for clinical treatment.</p><p><b>METHODS</b>A total of 20 school-age children with mild ASD were enrolled, and the intermediate visual and auditory continuous performance test (IVA-CPT) was used to assess their attention. A total of 20 children with attention deficit hyperactivity disorder (ADHD) and 40 healthy children were enrolled as controls.</p><p><b>RESULTS</b>Compared with the normal control group, the ASD group showed significantly lower scores of full scale attention quotient, full scale response control quotient, visual/auditory full scale response control quotient, visual/auditory prudence quotient, auditory perseverance quotient, visual consistency quotient, visual/auditory vigilance quotient, visual attention quotient, visual speed quotient, number of correct visual/auditory reactions, and visual mean reaction time of the second and third phases (P<0.05). Compared with the ADHD group, the ASD group showed significantly higher scores of full scale response control quotient and auditory consistency quotient (P<0.05), as well as significantly lower scores of visual vigilance quotient and visual speed quotient (P<0.05).</p><p><b>CONCLUSIONS</b>School-age children with mild ASD have attention deficit mainly manifested as the defect in the ability to focus attention, which is similar to the defect in children with ADHD, but ASD children have a lower degree of attention control impairment compared with children with ADHD. The defect in the ability to focus visual attention is more severe than that in the ability to focus auditory attention, while there is no significant difference between the defects in visual and auditory attention control.</p>


Subject(s)
Adolescent , Child , Female , Humans , Male , Attention , Attention Deficit Disorder with Hyperactivity , Psychology , Autism Spectrum Disorder , Psychology
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