1.Effects of Radix Angelica sinensis and Radix Hedysari ultrafiltration on oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation and its mechanism
Li-Rong WANG ; Ling-Yun WANG ; Xiao-Jing LI ; Hui-Lin ZHAO ; Yao-Hui HUO ; Hui CHAI ; Kai LIU
Chinese Pharmacological Bulletin 2024;40(8):1501-1509
Aim To investigate the effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration(RAS-RH)on oxidative stress and inflammatory injury of human umbilical vein endothelial cells(HUVECs)induced by ionizing radiation.Methods The model of HUVECs damage induced by 6 Gy X-rays was estab-lished.HUVECs were treated with different concentra-tions of RAS-RH(100,200,400 μg·L-1).The proliferative activity of HUVECs was detected by CCK-8 method,the structural changes of mitochondria were observed by transmission electron microscope,the level of ROS was detected by DCFH-DA probe,the change of intracellular mitochondrial membrane potential was detected by JC-1 kit,and the apoptosis and cycle were detected by flow cytometry.The contents of IL-6 and TNF-α in cells were detected by ELISA.The activities of MDA,CAT,SOD and GSH-PX were detected by biochemical kit.The gene expression levels of Nrf2,HO-1,NF-κB,eNOS and IL-6 were detected by qRT-PCR,and the expression levels of Nrf2,HO-1,eNOS,NF-κB,p-NF-κB and IL-6 protein were detected by Western blot.Results Compared with the model group,RAS-RH could increase the activity of HUVECs induced by ionizing radiation,decrease the rate of ap-optosis,decrease the level of intracellular ROS,re-duce the injury of intracellular mitochondria,increase the level of mitochondrial membrane potential,promote the expression of Nrf2,HO-1 and eNOS,and inhibit the expression of NF-κB and IL-6.Conclusions RAS-RH has anti-radiation,antioxidant and anti-in-flammatory effects,which may reduce the oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation by activating the activity of Nrf2/HO-1 signal pathway,thus promoting the activity of cell proliferation.
2.Retrospective cohort study on the relationship between Metformin and the risk of dementia in patients with type 2 diabetes mellitus
Houyu ZHAO ; Sanbao CHAI ; Yexiang SUN ; Peng SHEN ; Hongbo LIN ; Siyan ZHAN ; Feng SUN
Chinese Journal of Diabetes 2024;32(8):567-575
Objective To assess the association between Metformin use and the risk of dementia in patients with type 2 diabetes mellitus(T2DM).Methods The research data came from the big medical data platform of Yinzhou District,and we constructed a cohort of T2DM patients who had initiated treatment of Metformin or sulfonylurea since January 1,2009.The inverse probability of treatment weighting(IPTW)was used to control the baseline confounding factors,and the Cox regression model was used to estimate the HR(95%CI)of the association between Metformin use and dementia risk.Results The incidence rate of dementia in new users of Metformin(41181 persons)and sulfonylureas(38092 persons)was 128.4 per 100000 person years and 142.3 per 100000 person years respectively.Compared with sulfonylureas,the crude analysis with no adjustment for confounding factors showed that there was a negative association between the use of Metformin and the incidence of dementia,with an HR(95%CI)0.930(0.800~1.090).After adjusting for potential confounders with IPTW,Metformin was not significantly associated with the risk of dementia HR(95%CI)1.040(0.890~1.220).The subgroup analysis results for different baseline characteristics were consistent with the primary analysis results,and there were no statistically significant associations between Metformin and dementia incidence risk in all subgroups.Conclusions There is no significant association between the use of Metformin and the risk of dementia in T2DM patients in the Yinzhou District.
3.Effect of Yudian decoction on brain functional connectivity in schizophrenic model rats: an functional magnetic resonance imaging study
Bing BAI ; Sihan ZHAO ; Ming YU ; Yonghou ZHAO ; Jianbo CHAI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(10):870-875
Objective:To investigate alterations in brain functional connectivity (FC) in schizophrenia (SZ) model rats treated with Yudian decoction by using functional magnetic resonance imaging (fMRI).Methods:At 17th day of gestation in healthy SPF grade SD rats, a single intraperitoneal injection of methylazoxymethanol (MAM) (25 mg/kg) was used to induce abnormalities in monoamine neurotransmitters in pregnant female rats, thereby to establish a model of neural development abnormalities in the offspring. Four weeks old male offspring were selected as SZ model rats.Thirty SZ model rats were divided into model group, experimental group, and positive control group according to the body mass matching method, with 10 rats in each group. Additionally, 10 male offspring born to healthy female rats were selected as the blank control group.At 6 weeks of age, the rats in experimental group and positive control group were administered with Yudian decoction (1.54 g/kg) and risperidone (0.24 mg/kg) by gavage, respectively. The rats in blank control group and positive control group were administered with distilled water (6.7 mL/kg) by gavage.All the above interventions were conducted once a day for 14 consecutive days.The fMRI data were acquired from all samples using a 3.0 T MRI scanner. The bilateral hippocampus, bilateral prefrontal cortex, and bilateral striatum were designated as region of interest (ROI). FC comparisons between each pair of ROIs and whole-brain FC were conducted using two-sample t-test. Results:(1) Compared to the control group, the model group demonstrated enhanced whole-brain FC at the left cerebellar granular cell level (SIGMA: x=-2, y=-107, z=48) (cluster size=43, P<0.05, FWE adjusted under cluster-level). The experimental group exhibited increased whole-brain FC at the left cerebellar molecular layer (SIGMA: x=-5, y=-152, z=36) compared to the model group (cluster size=48, P<0.05, FWE adjusted under cluster-level). (2) Using the bilateral hippocampus as ROI, the positive control group exhibited enhanced FC at the deep layer of the superior colliculus (SIGMA: x=13, y=-77, z=27) compared to the model group (cluster size=88, P<0.05, FWE adjusted under cluster-level). The blank control group displayed decreased FC at the right granular insular cortex (SIGMA: x=43, y=19, z=9) compared to the model group (cluster size=125, P<0.05, FWE adjusted under cluster-level). Utilizing the bilateral prefrontal cortex as ROI, the experimental group showed reduced FC at the left cerebellar molecular layer (SIGMA: x=-14, y=-128, z=48) compared to the blank control group (cluster size=68, P<0.05 FWE adjusted under cluster-level). Conclusion:Schizophrenia is associated with abnormal whole-brain functional connectivity, notably characterized by enhanced functional connectivity in the hippocampal region.Yudian decoction demonstrates the capability to inhibit activity in the prefrontal cortex.
4.Expression level of serum UBE2C and TRIM27 in patients with endometrial cancer and their correlation with pathological parameters
Fei CHAI ; Zhenwen CHEN ; Hongyan LIU ; Su LI ; Yuanyuan GONG ; Yingying ZHAO
The Journal of Practical Medicine 2024;40(13):1808-1813
Objective To investigate the expression level of serum ubiquitin-conjugating enzyme 2C(UBE2C)and tripartite motif-containing protein 27(TRIM27)in patients with endometrial cancer(EC)and their correlation with pathological parameters.Methods A total of 96 EC patients from March 2020 to March 2023 were selected as EC group;65 patients with endometrial atypical hyperplasia(EAH)as EAH group,and 80 healthy subjects as the control group.Enzyme linked immunosorbent assay was applied to analyze the expression level of serum UBE2C and TRIM27.The relationship between serum UBE2C,TRIM27,and pathological data was analyzed;receiver operating characteristic was applied to evaluate the predictive value of serum UBE2C and TRIM27 level for EC.Results The level of serum UBE2C and TRIM27 of EC patients was obviously higher than that in healthy subjects(P<0.05),and was correlated with tumor diameter,tumor differentiation,lymph node metastasis,FIGO stage,muscle layer invasion depth,cervical involvement,estrogen receptor expression,and progestogen receptor expression(P<0.05).There was positive correlation between serum UBE2C and TRIM27(r=0.475,P<0.001);and the level of serum UBE2C and TRIM27 was positively correlated with tumor diameter,lymph node metastasis,FIGO stage,and depth of musclular invasion,but negatively with tumor differentiation,estrogen receptor expression,and progestogen receptor expression(P<0.05).The combination of UBE2C and TRIM27 had obviously higher AUC in evaluating EC than single detection(ZUBE2C-combination=3.406,P<0.001,ZTRIM27-combination=3.285,P=0.001).Conclusion The expression level of UBE2C and TRIM27 in serum of EC patients is up-regulated,which is closely related to pathological parameters.The level of serum UBE2C and TRIM27 can provide reference for early diagnosis of EC.
5.Protective effect and mechanism of Scutellariae Radix on fibrosis in diabetic cardio-myopathy based on network pharmacology and cytology experiments
Kaijia SHI ; Cai LUO ; Yangyang ZHAO ; Xinglin ZHU ; Jinxuan CHAI ; Junli GUO ; Wei JIE
Chinese Journal of Arteriosclerosis 2024;32(5):386-394
Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy(DCM).Methods The technology platform of Chinese medicine system pharmacology(TCMSP)and the small molecule drug target prediction(Swiss Target Prediction)platform were used to excavate the active components of Scutellariae Radix and the target of its response.DCM related disease gene targets were screened using GeneCards,Disgene,UniPort and OMIM databases,and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram.Cytoscape 3.9.1 software was a-dopted to visualize the key target network.Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM,and draw pathway maps through the KEGG database.H9c2 and AC16 cardio-myocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group,35 mmol/L D-glucose as the high glucose group,and 10 μmol/L Baicalin was used for intervention.The levels of TGF-β1,collagen Ⅰ(COL Ⅰ)and collagen Ⅲ(CO LⅢ)mRNA were detected by RT-qPCR,and the expression of Smad2/3,p-Smad2/3,COL Ⅰ and COL Ⅲprotein were detected by Western blot,TGF-β1 level in supernatant was assessed by ELISA.Results Through the a-bove platform,a total of 33 effective ingredients including Baicalin,441 core targets,and 1 884 DCM disease genes were retrieved,150 core genes for treating DCM with Scutellariae Radix were obtained.The drug-disease interacted genes such as TGF-β1,TP53,MMP-9 and IL-6 were obtained through String PPI,KEGG signaling pathways such as MAPK and PI3K/Akt were enriched.In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1,COL Ⅰ and COL Ⅲ mRNA levels,p-Smad2/3,COL Ⅰ and COL Ⅲ protein levels,and signifi-cantly increased the content of TGF-β1 in the supernatant,while Baicalin weakened its expression.Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets,among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.
6.Intervention effect and mechanism of breviscapine on hepatic fibrosis in rats
Dandan WEI ; Shanshan LI ; Minghao ZHANG ; Yurun WEI ; Hongling WANG ; Shuangshuang CHAI ; Jingjing YIN ; Min ZHANG ; Han ZHAO ; Zongyao WU ; Kuicheng ZHU ; Qingbo WANG
China Pharmacy 2024;35(6):671-677
OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis (HF) in rats based on the transforming growth factor-β(1 TGF-β1)/Smad2/extracellular signal-regulated protein kinase 1(ERK1) and Kelch-like epichlorohydrin-associated protein 1(Keap1)/nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathways. METHODS Totally 60 rats were randomly divided into normal control group, model group, breviscapine low-dose, medium-dose and high-dose groups (5.4, 10.8, 21.6 mg/kg), and colchicine group (positive control, 0.45 mg/kg), with 10 rats in each group, half male and half female. Except for the normal control group, HF model of the other groups was induced by carbon tetrachloride. Subsequently, each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase (ALT) and aspartate aminotransferase (AST)in serum, those of ALT, AST, superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH- Px) in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1, Smad2, ERK1, Nrf2, Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group, the model group showed large areas of white nodular lesions in the liver, obvious inflammatory cell infiltration and collagen fiber deposition. The body weight, the levels of SOD and GSH-Px in liver tissue, the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group (P<0.05); the liver coefficient, the percentage of Masson staining positive area, ALT and AST levels of serum and liver tissue, MDA level of liver tissue, the protein and mRNA expressions of TGF-β1, Smad2, ERK1 and Keap1 were significantly increased (P<0.05). Compared with the model group, the liver lesions of rats in each drug group were improved, and the above quantitative indexes were generally reversed (P<0.05). CONCLUSIONS Breviscapine has a good intervention effect on HF rats, which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.
7.Interpretation and reflection on the Measures for the Administration of Standards for Medicinal Products
Mengxia ZHAO ; Lina SUN ; Dan XU ; Wen CHAI ; Xuekong JIANG ; Zhihai MAO ; Shengliang HE
China Pharmacy 2024;35(7):783-786
In July 2023, the National Medical Products Administration issued the Measures for the Administration of Standards for Medicinal Products (hereinafter referred to as the Measures). This article interprets the main content of the Measures, and analyzes its shortcomings as unclear definition of the drug standard code and the goals of drug standard information construction. It is recommended that the national drug regulatory department promptly apply to the standardization authority for the confirmation of the drug standard code “YB” letter, and the drug standard code and numbering rules would be included in the next round of amendments to the Measures. It is necessary to clarify the construction goals of the information system for drug standards at the same time, and build a national drug standard data-sharing platform based on the basic framework of user interface layer, computing processing layer, and data storage layer. Digital drug standards will be free, and access and download services for the public will be provided.
8.Research progress on the improvement mechanism of traditional Chinese medicine compounds and active ingredients in schizophrenia
Xinhui YAO ; Yonghou ZHAO ; Jianbo CHAI ; Ming YU ; Xiujie QU
China Pharmacy 2024;35(9):1151-1156
Schizophrenia has various obstacles in cognition, thinking, emotion, behavior and other aspects; it belongs to the category of “madness” in traditional Chinese medicine (TCM). Once schizophrenia occurs, multiple factors are often intertwined, and a single therapy is difficult to be effective. At present, TCM compounds and active ingredients have significant effects in the clinical treatment of schizophrenia, which is an important direction for the development of new drugs for schizophrenia. This article summarizes the molecular mechanism of TCM compounds and active ingredients in the treatment of schizophrenia. It is found that Wendan decoction and Yudian decoction can inhibit the apoptosis of hippocampal cells by activating BDNF/TrKB/CREB signaling pathway; quercetin and icariin can promote neural development and regeneration by activating NMDA/ERK signaling pathway; Wendan decoction and icariin can maintain neural cell homeostasis by activating PI3K/AKT signaling pathway; Bushen zhuangyang capsule can enhance learning and memory abilities by activating CaMKⅡ signaling pathway; formulas such as Huatan huoxue tongzhi formula can enhance intercellular information transmission by inhibiting PKC signaling pathway; α-humulene and others can restore nerve cell function by inhibiting NRG1/ErbB4 signaling pathway. TCM compounds and active ingredients can improve schizophrenia by intervening in the above-mentioned signaling pathways.
9.Analysis of the efficacy and prognosis of radiotherapy in acute leukemia with extramedullary infiltration
Wenbin LEI ; Hui LIU ; Yan ZHANG ; Yinghao LU ; Yi HUANG ; Ying CHEN ; Rui GAO ; Xiao CHAI ; Yun ZHAN ; Jie XIONG ; Lingyun WANG ; Lei LIU ; Jishi WANG ; Peng ZHAO
Chongqing Medicine 2024;53(4):547-554
Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95%CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.
10.Prevention and Treatment of Schizophrenia by Traditional Chinese Medicine Targeting PI3K/Akt Signaling Pathway: A Review
Haiyuan WU ; Jianbo CHAI ; Ming YU ; Yonghou ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):280-289
As one of the most difficult-to-cure neuropsychiatric disorders in clinical practice, schizophrenia is mainly manifested by behavioral abnormalities and multidimensional cognitive dysfunction, and the recurrence rate and disability rate of the disease are increasing year by year, which seriously affects patients' social functioning and quality of life, and even threatens the physical and mental health of the surrounding population. At present, the treatment of schizophrenia is mainly based on antipsychotic drugs combined with psychotherapeutic techniques, which have limited long-term therapeutic effects and a high relapse rate. Traditional Chinese medicine (TCM) boasts the advantages of multi-targets, multi-pathways, multi-links, and multi-levels, and plays a crucial role in the prevention and treatment of schizophrenia and its prognosis. Phosphatidylinositol 3-kinase (PI3K) is widely present in cells and is involved in the regulation of protein synthesis and apoptosis, and the different isoforms of protein kinase B (Akt) are of great significance in cell growth, oxidative stress, neuronal development and other processes. In recent years, a large number of studies have found that the PI3K/Akt signaling pathway is closely related to schizophrenia. Through regulating the PI3K/Akt signaling pathway, TCM monomers and TCM compounds mainly affect key signaling molecules such as mammalian target of rapamycin (mTOR), glycogen synthase kinase (GSK), glucose transporter (GLUT) for glucose uptake and transport, and nuclear factor E2-associated factor 2 (Nrf2), which organize the intracellular network of centers and regulate the formation and plasticity of neuronal synapse, and they play an important role in mitigating schizophrenia by regulating the processes of cell proliferation, migration and apoptosis of neurons, and has the advantages of multi-targets, all-encompassing and low toxicity. This article analyzes and explains the mechanism of TCM intervention in the PI3K/Akt signaling pathway against schizophrenia, in order to provide a theoretical basis and reference for the prevention and treatment of schizophrenia by TCM.

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