1.Huanglian-Renshen-Decoction Maintains Islet β-Cell Identity in T2DM Mice through Regulating GLP-1 and GLP-1R in Both Islet and Intestine.
Wen-Bin WU ; Fan GAO ; Yue-Heng TANG ; Hong-Zhan WANG ; Hui DONG ; Fu-Er LU ; Fen YUAN
Chinese journal of integrative medicine 2025;31(1):39-48
OBJECTIVE:
To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine.
METHODS:
The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively.
RESULTS:
HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01).
CONCLUSION
HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals
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Glucagon-Like Peptide 1/metabolism*
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Diabetes Mellitus, Type 2/metabolism*
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Glucagon-Like Peptide-1 Receptor/metabolism*
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Insulin-Secreting Cells/pathology*
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Drugs, Chinese Herbal/pharmacology*
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Male
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Blood Glucose/metabolism*
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Insulin/blood*
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Mice
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Intestinal Mucosa/pathology*
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Apoptosis/drug effects*
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Cell Proliferation/drug effects*
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Islets of Langerhans/pathology*
2.Research status on the mechanism of action of Astragaloside Ⅳ on cardiovascular diseases
Er-Dan XIN ; Yu-Gui ZHANG ; Tian-Tian BIAN ; Ding-Cai MA ; Zhe WANG ; Mao-Mao WANG ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(17):2580-2585
Asragaloside Ⅳ(AS-Ⅳ)is one of the active ingredients of Astragalus membranaceus,and AS-Ⅳ can play a protective role in cardiovascular diseases by inhibiting inflammatory response,inhibiting cardiomyocyte apoptosis,improving myocardial ischemia reperfusion injury,regulating lipid metabolism,promoting cardiac vascular regeneration,inhibiting myocardial fibrosis,and improving myocardial hypertrophy.In this paper,we reviewed the relevant literature on the prevention and treatment of cardiovascular diseases of AS-Ⅳ,and summarized and analyzed its role and mechanism,in order to provide a reference for the in depth research on cardiovascular diseases and the development and application of drugs.
3.Loss-of-function CFTR p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis.
Jian-Wen HOU ; Xiao-Liang LI ; Li WANG ; Cong-Ling DAI ; Na LI ; Xiao-Hui JIANG ; Yue-Qiu TAN ; Er-Po TIAN ; Qin-Tong LI ; Wen-Ming XU
Asian Journal of Andrology 2023;25(1):58-65
Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.
Humans
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Animals
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Mice
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Male
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Mutation, Missense
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Retrospective Studies
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Cystic Fibrosis Transmembrane Conductance Regulator/genetics*
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Infertility, Male/genetics*
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Mutation
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Vas Deferens/abnormalities*
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Spermatogenesis/genetics*
4.Pharmacological insights into autophagy modulation in autoimmune diseases.
Ming-Yue WU ; Er-Jin WANG ; Du FENG ; Min LI ; Richard D YE ; Jia-Hong LU
Acta Pharmaceutica Sinica B 2021;11(11):3364-3378
As a cellular bulk degradation and survival mechanism, autophagy is implicated in diverse biological processes. Genome-wide association studies have revealed the link between autophagy gene polymorphisms and susceptibility of autoimmune diseases including systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), indicating that autophagy dysregulation may be involved in the development of autoimmune diseases. A series of autophagy modulators have displayed protective effects on autoimmune disease models, highlighting the emerging role of autophagy modulators in treating autoimmune diseases. This review explores the roles of autophagy in the autoimmune diseases, with emphasis on four major autoimmune diseases [SLE, rheumatoid arthritis (RA), IBD, and experimental autoimmune encephalomyelitis (EAE)]. More importantly, the therapeutic potentials of small molecular autophagy modulators (including autophagy inducers and inhibitors) on autoimmune diseases are comprehensively analyzed.
5.Formulation regularity and thinking of adjuvant sleep-improving Chinese medicinal health products.
Er Xun Re-Yi-la TU ; Yan LIAO ; Na YUE ; Rui ZHANG ; Chun WANG ; Jian-Jun ZHANG
China Journal of Chinese Materia Medica 2021;46(13):3228-3233
To summarize and analyze the current adjuvant sleep-improving Chinese medicinal health products,this study retrieved the information on health products with the sleep-improving effect published by the Department of Special Food Safety Supervision and Management,State Administration for Market Regulation( SMAR),which was statistically analyzed with Microsoft Excel and TCMISS for the characteristics of formulations. A total of 435 sleep-improving health products were collected,including 344 ones containing Chinese herbal medicines. Among them,413 health products were not suitable for adolescents,neither 194 for pregnant women. Ten Chinese herbal medicines showed a frequency of use ≥40,with 1 095 times( 73. 1%) in use. Through unsupervised hierarchical entropy-based clustering of the above Chinese herbal medicines of health products( degree of support of 45 and confidence coefficient of0. 7),12 new formulas were obtained. The composition of Chinese herbal medicines was consistent with the principles of improving sleep in traditional Chinese medicine( TCM) theories,i. e.,replenishing the heart and spleen,nourishing blood,calming the nerves,nourishing Yin,reducing internal heat,communicating the heart and kidney,replenishing Qi,relieving convulsions,clearing heat,resolving phlegm,regulating the middle warmer,soothing the liver,relieving heat,and calming the heart. According to TCM theories,syndrome differentiation was performed based on the existing sleep-improving health products,followed by data mining and analysis according to the formulation regularity,aiming to provide new ideas for the development of new Chinese medicinal health products. In particular,attention should be attached to the requirements of special populations to provide a basis for follow-up studies,exert the advantages of TCM,and lay a foundation for Chinese medicinal health products to service the public.
Adolescent
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China
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Data Mining
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Drugs, Chinese Herbal
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Female
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Humans
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Medicine, Chinese Traditional
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Pregnancy
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Sleep
6.Impact of KIT D816 mutation on salvage therapy in relapsed acute myeloid leukemia with t(8;21) translocation.
Ben Fa GONG ; Ye Hui TAN ; Ai Jun LIAO ; Jian LI ; Yue Ying MAO ; Ning LU ; Yi DING ; Er Lie JIANG ; Tie Jun GONG ; Zhi Lin JIA ; Yu SUN ; Bing Zong LI ; Shu Chuan LIU ; Juan DU ; Wen Rong HUANG ; Hui WEI ; Jian Xiang WANG
Chinese Journal of Hematology 2018;39(6):460-464
Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.
Antineoplastic Combined Chemotherapy Protocols
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Cytarabine
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Humans
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Leukemia, Myeloid, Acute/therapy*
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Prognosis
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Retrospective Studies
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Salvage Therapy
7.Application progress of proteomic in pharmacological study of Chinese medicinal formulae.
Yu-Qian LIU ; Shu-Yu ZHAN ; Yu-Er RUAN ; Zhi-Yan ZUO ; Xiao-Ming JI ; Shuai-Jie WANG ; Bao-Yue DING
China Journal of Chinese Materia Medica 2017;42(20):3873-3879
Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae.
8.Study of incidental extracerebral findings on brain nonenhanced magnetic resonance imaging
ting Ting YAO ; bin Wei YUE ; er Xiao WEI ; Dan WANG ; Jing LU ; Jing LI ; hua Yue LI
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(11):1528-1533
Objective· To explore the frequency, nondetection rate, and clinical importance of incidental extracerebral findings (IECFs)on brain nonenhanced magnetic resonance imaging(MRI). Methods · The MRI data of 7 930 cases with suspected intracerebral lesionin were retrospectively analyzed. IECFs were categorized as E1 (clinically unimportant, e.g., sinus mucosal thickening), E2 (likely unimportant, e.g.,pharyngeal mucosal symmetrical thickening), and E3 (potentially important, e.g., pharyngeal mucosal asymmetrical thickening). The nondetection rate was determined by comparing the results of the structured approach with the initial MRI reports. The medical records were examined for patients with E3 IECFs to assess clinical importance and outcome of these lesions. Results · A total of 5 992 IECFs were found in 4 213 patients (53.13%, 4 213/7 930). IECFs with E1 was 82.2% (4 924/5 992), E2 was 16.6% (995/5 992) and E3 1.2% (73/5 992). Overall IECFs and E1 findings were occurred more commonly in male patients (P=0.000, P=0.024). And the statistically significant difference was also found among different age groups (P=0.000). The nondetection rate was 56.9% (3 409/5 992) for overall IECFs and 32.9% (24/73) for E3 IECFs. Of the 73 patients with E3 IECFs, 34 (46.6%) received final diagnosis and appropriate treatment during the study period. Conclusion · IECFs are prevalent in clinical patients on brain MRI with a nondetection rate of 32.9% for potentially important (E3) findings. The reporting of IECFs according to clinical importance is helpful for patients' management.
9.Study on Quality Control Method of Yinqiao Chaihuang Granules
xian Li ZHANG ; fang Xue WANG ; ya Jing CAO ; Xiao LI ; hong Zi LI ; fei Fei LI ; ning Zhi LI ; juan Er NING ; jiao Meng SONG ; Yue WEI
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(11):82-85
Objective To establish the quality control method of Yinqiao Chaihuang Granules.Methods Lonicerae Japonicae Flos, Bupleuri Radix, Scutellariae Radix and Glycyrrhizae Radix et Rhizoma in Yinqiao Chaihuang Granules were identified by TLC, and the content of forsythoside A was detected by HPLC. Results Under the selected chromatographic conditions, TLC spots were clear, the separating was good, and non-interference was found in negative control. Forsythoside A in calibration curve showed good linearity in the range of 0.029 6–0.474 μg, with average recovery of 99.73%, RSD=1.18%. Conclusion The method is accurate and simple, which can be used for the quality control of Yinqiao Chaihuang Granules.
10.Relationship between microbleeds on susceptibility-weighted MRI and newly-developed depression in patients after mild traumatic brain injury
Ping ZHU ; Yue-Hua LI ; Xiao-Bing LI ; Xiao-Er WEI ; Xuan WANG
Chinese Journal of Clinical Medicine 2017;24(1):31-36
Objective:To explore the relationship between abnormality on susceptibility-weighted imaging (SWI)and newly-developed depression after mild traumatic brain injury.Methods:Totally 200 brain injury patients with routine CT and MRI were examined.All patients underwent MRI including conventional MR sequences and SWI.The number and volume of microbleed lesions were semi-automatically outlined and manually counted.All patients were followed up with the Structured Clinical Interview for DSM-Ⅳ Axis I Disorders (SCID-Ⅳ)within 1 year after TBI.Results:The difference in microbleed lesions on SWI was compared between the depressive and non-depressive groups.The depressive group had a higher rate of abnormality on SWI than which in the non-depressive group (P<0.001 ).Among patients that had exhibited microbleed lesions,the number and volume of lesions were greater in the depressive group than the non-depressive group (allP<0.001). These differences in numbers and volume of lesions were found only at the frontal,parietal,and temporal lobes (all P<0.001).Among patients that had exhibited microbleed lesions,the number and volume of lesions in other areas were not significantly different between the depressive and non-depressive groups.Conclusions:SWI was useful to identify the microbleed lesions after mild TBI.The distribution range and location of microbleed lesions were correlated with depression after TBI.

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