1.Preparation and characterization of curcumin nanomicelles and evaluation of in vitro hepatoprotective activity against alcohol liver disease
Luhui LI ; Guangping GENG ; Lei XU ; Zhikun ZHANG ; Xiaohui PU
China Pharmacy 2024;35(10):1203-1208
OBJECTIVE To prepare and characterize curcumin nanomicelles (hereinafter referred to as Cur/mPEG-PBLA micelles), and to evaluate the in vitro hepatoprotective activity against alcohol liver disease (ALD). METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly(ethylene glycol)-poly(β-benzyl-L-aspartate) (mPEG-PLGA) as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed, and particle size, polydispersity index, Zeta potential, encapsulation efficiency and drug loading content were all detected. The in vitro release, pH stability, thermal stability, dilution stability, storage stability, plasma stability tests, and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects, Cur reference solution as reference, to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light, with a spherical shape and uniform distribution. The average particle size was about 140 nm, and the polydispersity index was less than 0.3. Zeta potential was (-8.15±0.05) mV; the encapsulation efficiency was (73.26±3.16)%, and the drug loading content was (4.87± 0.42)%. The cumulative release of Cur reference substance was close to 80% at 10 h; the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution; Cur/mPEG-PBLA micelles showed good dilution stability, storage stability and plasma stability, and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells; after 48 h of application, the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration (P<0.05). CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur, delayits degradation rate, and have better in vitro hepatoprotective activity against ALD.
2.Homozygous variants of the new allele A4GALT result in rare p blood groups
Ziyi HE ; Yingming HU ; Guangping LUO ; Xiaomei JIE ; Menghui BEI ; Xianguo XU
Chinese Journal of Laboratory Medicine 2024;47(11):1345-1348
The proband was a 33-year-old pregnant woman (G4P1) who suffered spontaneous abortion in the first 3 months of pregnancy without a history of blood transfusion or transplantation. The fourth pregnancy was clinically diagnosed with threatened abortion, and a cesarean section was performed on June 28, 2023, at the Obstetrics and Gynecology Department of Dongguan Hospital of Traditional Chinese Medicine. During cross-matching tests, unexpected antibodies were detected in the proband′s plasma, which could not be specifically identified, and no suitable donor red blood cells could be found. The blood samples were sent to the Blood Transfusion Laboratory of Dongguan Blood Center. The laboratory used serology to identify the erythrocyte phenotype of the proband and confirmed the proband as having a rare p blood group. The unexpected antibody was identified as anti-PP1P K, and gene sequencing of the proband revealed that the new allele A4GALT* (c.100G>A+c.418_428delins) was homozygous, which is speculated to cause changes in the polypeptide chains p.Veral34ile and p.GERln140TRPFS *73, and inactivation of α1, 4-galactosyltransferase. At the same time, another new allele A4GALT*c.100G>A was found in family members, and it was predicted that the single change of p.Val34Ile caused by this mutation would not affect protein function or enzyme activity.
3.The challenging blood cross-matching and resolution for multiple myeloma patients in different disease stages
Ying LU ; Baoying FENG ; Lijuan XU ; Peibin LAI ; Lingling LIU ; Guangping LUO ; Qing YUAN
Chinese Journal of Blood Transfusion 2022;35(3):257-261
【Objective】 To explore the challenging blood cross-matching and resolution for multiple myeloma (MM) patients in different disease stages. 【Methods】 For a patient who was first diagnosed as MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method and tube test. When the major side of cross-matching was agglutinated, the patient’s plasma was cross matched with donors’ red blood cell (RBC) by polybrene test, then plasma dilution cross matched with donors’ RBC by microcolumn gel method. For a patient who was diagnosed as recurrent refractory MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method. 【Results】 1) Case 1 was a first-visit outpatient. The major side of microcolumn cross-match test was agglutinated with the shape of fine line. The result of tube method also showed agglutination of major sides, and the rouleaux were detected by the microscopy. Then polybrene method and microcolumn gel method (after plasma diluted) were applied for cross-matching again with the above two donors’ blood and showed compatibility. 2) Case 2 was a recurrent refractory MM patient. The major and minor sides of microcolumn cross-match test were both agglutinated with the shape of granular. The patient was treated with anti-CD38 monoclonal antibody. The RBCs, after treated with dithiothreitol (DTT) was used to cross match with patient plasma by microcolumn test, and the result was compatible. 【Conclusion】 Polybrene method and microcolumn gel method after plasma diluted are suitable for blood cross-matching of newly diagnosed MM patients, also for those treated with CD38 monoclonal antibody, as the drug interference with cross-matching can be eliminated by DTT.
4.Discovery of novel diarylamides as orally active diuretics targeting urea transporters.
Shun ZHANG ; Yan ZHAO ; Shuyuan WANG ; Min LI ; Yue XU ; Jianhua RAN ; Xiaoqiang GENG ; Jinzhao HE ; Jia MENG ; Guangying SHAO ; Hong ZHOU ; Zemei GE ; Guangping CHEN ; Runtao LI ; Baoxue YANG
Acta Pharmaceutica Sinica B 2021;11(1):181-202
Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,
5. Tolvaptan attenuates atrial remodeling in rats undergoing chronic intermittent hypoxia via miRNA-21
Zuowang MA ; Kai ZHANG ; Weiding WANG ; Ruimeng LIU ; Yuanyuan XU ; Yue ZHANG ; Meng YUAN ; Guangping LI
Chinese Journal of Cardiology 2019;47(8):614-621
Objective:
To investigate the effects and potential mechanisms of tolvaptan on chronic intermittent hypoxia (CIH)-induced atrial remodeling in rats.
Methods:
A total of 45 Sprague-Dawley rats were divided into 3 groups by the random number table: control group, CIH group (6 h/d for 30 days), CIH plus tolvaptan group (8 mg·kg-1·d-1 per gavage for 30 days). Echocardiography examination was performed after 30 days. Thereafter, 5 rats were randomly chosen for histology evaluation, 5 for molecular biological examinations and another 5 rats underwent isolated heart electrophysiology study in each group. Protein and mRNA expression levels of miRNA-21, Spry1, PTEN, ERK/p-ERK, MMP-9, PI3K, AKT/p-AKT were detected.
Results:
Compared to the rats in control group, rats in the CIH group showed higher atrial interstitial collagen deposition (
6.Tolvaptan attenuates atrial remodeling in rats undergoing chronic intermittent hypoxia via miRNA-21
Zuowang MA ; Kai ZHANG ; Weiding WANG ; Ruimeng LIU ; Yuanyuan XU ; Yue ZHANG ; Meng YUAN ; Guangping LI
Chinese Journal of Cardiology 2019;47(8):614-621
Objective To investigate the effects and potential mechanisms of tolvaptan on chronic intermittent hypoxia (CIH)?induced atrial remodeling in rats. Methods A total of 45 Sprague?Dawley rats were divided into 3 groups by the random number table: control group, CIH group (6 h/d for 30 days), CIH plus tolvaptan group (8 mg·kg-1·d-1 per gavage for 30 days). Echocardiography examination was performed after 30 days. Thereafter, 5 rats were randomly chosen for histology evaluation, 5 for molecular biological examinations and another 5 rats underwent isolated heart electrophysiology study in each group. Protein and mRNA expression levels of miRNA?21, Spry1, PTEN, ERK/p?ERK, MMP?9, PI3K, AKT/p?AKT were detected. Results Compared to the rats in control group, rats in the CIH group showed higher atrial interstitial collagen deposition (P<0.001), increased atrial fibrillation inducibility (P=0.022). The results of immunohistochemistry staining showed that the mean optical density (MOD) of ERK, p?ERK and MMP?9 were significantly increased (all P<0.05), the MOD of Spry1 and PTEN were significantly decreased (both P<0.05), above changes could be significantly reversed by cotreatment with tolvaptan. No significant differences were detected in PI3K and AKT among the three groups (P>0.05). In addition, compared with rats in control group, mRNA levels of miRNA?21, MMP?9, PI3K, AKT, and protein levels of ERK, p?ERK, MMP?9 were significantly increased in CIH group(all P<0.05), whereas protein levels of Spry1, PI3K, p?AKT were significantly decreased (all P<0.05). Above changes could be significantly attenuated. Conclusions CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA?21/Spry1/ERK/MMP?9 and miRNA?21/PTEN/PI3K/AKT signaling pathways.
7.Analysis on prevalence of chronic obstructive pulmonary disease based on pulmonary function screening in Changchun urban area of Jilin province
Xueyang ZHANG ; Ji MA ; Guangping MENG ; Qi WANG ; Wei LI ; Yanling XU ; Jie ZHANG ; Peng GAO
Journal of Jilin University(Medicine Edition) 2017;43(5):1047-1052
Objective:To investigate the prevalence of chronic obstructive pulmonary disease (COPD) in the adults aged 40 years old and over in Changchun urban area,and to clarify the important significance of early application of pulmonary function examination.Methods:With the help of community workers,10 communities which around Second Hospital of Jilin University were selected and the participants aged 40 years old and over were randomly collected.COPD questionnaire and pulmonary function examination were conducted in all subjects.The patients with COPD were diagnosed according to the criteria established by the Global Initiative for COPD (GOLD).The patients with COPD were divided into the diagnostic group and undiagnostic group,then the patients with COPD who had smoking history were divided into smoking cessation group and smoking group.The pulmonary function of each groups were compared.Results:A total of 1 392 participants aged 40 years old and over were recruited in this survey,including 568 males and 824 females,and their average age was (59.59±6.60) years.Totally 176 subjects were diagnosed as COPD,and the prevalence was 12.64%.Furthermore,160 of them were newly diagnosed,which showed the undiagnostic rate of COPD was 90.91 %.Among the 176 patients with COPD,16 had been confirmed before,which meant only 9.09% patients got the accurate diagnose before.The analysis of high-risk factor (smoking) showed that the population had an increased prevalence of COPD (20.71%) compared with non-smokers (8.8%) (P< 0.05).The correlational analysis between smoking index and the pulmonary function of the patients with COPD showed that all of the pulmonary function indexes except forced vital capacity (FVC%) and maximum midexpiratory flow (MMEF%) in smoking cessation group were descended along with the increase of smoking index (P<0.05).All of the pulmonary function indexes except FVC% in smoking group were descended along with the increase of smoking index (P < 0.05).Conclusion:The high prevalence and underdiagnostic rate of COPD are found in the residents aged 40 years old and over in Changchun urban area.More patients with COPD should be screened by performing pulmonary function examination to treat them at an early stage.
8.MicroRNA expression profiles in early mycosis fungoides
Guangping WANG ; Nana NI ; Xiaowei ZHOU ; Ying YANG ; Hao SONG ; Sijian WEN ; Hao CHEN ; Xiulian XU ; Jianfang SUN
Chinese Journal of Dermatology 2016;49(11):785-788
Objective To screen microRNAs(miRNAs)related to early mycosis fungoides(MF). Methods A high?throughput miRNA PCR array was used to determine miRNA expression profiles in skin lesions of 6 patients with early MF (early MF group) and 6 patients with lichen planus (control group), followed by screening of differentially expressed miRNAs between the two groups. Then, real?time fluorescence?based quantitative PCR(RT?qPCR)was performed to verify the differentially expressed miRNAs in lesional specimens from 13 patients with early MF and 13 patients with eczema or lichen planus, as well as in Myla cells and normal human T?lymphocytes. Results The high?throughput miRNA PCR array showed that the expressions of hsa?miR?378a?5p, hsa?miR?107 and hsa?miR?302c?3p were significantly higher in the early MF group than in the control group(all P<0.05). For skin lesions, the results from RT?qPCR were similar to those from the miRNA array assay. Compared with normal human peripheral blood T?lymphocytes, Myla cells showed significantly increased expressions of hsa?miR?378a?5p and hsa?miR?107, which was consistent with the results from the miRNA array assay. However, no significant difference was observed in the expression of hsa?miR?302c?3p between the two kinds of cells. Conclusion MiRNA expression profiles in early MF are different from those in inflammatory skin diseases.
9.Clinicopathologic analysis of 60 cases of pityriasis lichenoides et varioliformis acuta
Xiulian XU ; Guangping WANG ; Hao CHEN ; Yiqun JIANG ; Xuesi ZENG ; Hong JIA ; Jianfang SUN
Chinese Journal of Dermatology 2015;48(2):90-93
Objective To explore the clinicopathologic features of pityriasis lichenoides et varioliformis acuta (PLEVA).Methods A retrospective analysis was performed.Clinical and histological data were collected from 60 patients with PLEVA.The clinicopathologic features of PLEVA were analyzed.Results Among the 60 patients with PLEVA,32 (53.3%) were aged 2-18 years,and 28 (46.7%) aged 19-49 years.Skin lesions were distributed in a diffuse pattern in 50 (83.3%) patients,in a central pattern in 2 (3.3%) patients,and in a peripheral pattern in 8 (13.4%) patients.Nineteen (31.6%) patients had a history of upper respiratory infection.Histopathological examination revealed liquefactive degeneration of basal cells and perivasculitis in the dermis in all the 60 cases,neutrophil abscess formation in the stratum corneum in 26 (43.3%) cases,keratinocyte necrosis in the epidermis in 41 (68.3%) cases,generalized liquefactive degeneration in 30 (50.0%) cases,migration of lymphocytes into the epidermis in 43 (71.6%) cases,Pautrier's microabscess formation in 2 cases,varying degrees of extravasation of erythrocytes into the epidermis in 46 (76.7%) cases,fibrinoid necrosis of blood vessel walls in the dermis in 3 cases.PLEVA progressed into granuloma fungoides in 1 patient.Twenty patients underwent immunohistochemical examination,and 3 of them showed monoclonal hyperplasia of T cells.Conclusions PLEVA has characteristic clinical manifestations,and the combination of pathological and clinical examination is the gold standard for its diagnosis.
10.Compatibility Analysis ofShenandGuiinShen-Gui-FangFormula
Benxi LIU ; Guangping DONG ; Benlei YANG ; Jiapeng XU ; Huixiang YU ; Jifeng LUO
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(7):1444-1448
This study was aimed to explore the relationship between the Shen-Gui-Fang(SGF) formula of different proportions and treatments for diseases with the method of bibliometrics. A total of 49 formulae of SGF from ancient books of traditional Chinese medicine (TCM) were retrieved and the database was established in order to analyze the origin of herbal medicine and the relationship with the ratio of the key medicinal material, as well as the treatment for major diseases. The results showed that 49 SGF formulae were mainly used in the treatment of internal disorders for 16 times (32.65%), gynecological disorders for 17 times (34.69%) and pediatric disorders for 8 times (16.32%). Guistanded forAngelica sinensis. There were 3 types ofShen, which werePanax ginsengfor 40 times,Codonopsis pilosulafor 8 times, andSophora flavescensfor 1 time. The ratio betweenP. ginsengandA. sinensiswas less or equal to 1. The ratio betweenC. pilosulaandA. sinensiswas usually more than 1. The formulae with the highest frequency were in the treatment of internal medicine and gynecological diseases. Statistical analysis was used to find the application features and rules of the combination ofP. ginsengandA. sinensisin SGF formula, in order to provide theoretical evidences and references for clinical medication selection and new medication research.

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