Table of Content

Volume 26 Issue 1
26 January 2021

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Tangshen formula promotes cellular cholesterol efflux in HG-induced mTECs by suppression of TGF-β1/Smad3 pathway

LIU Peng, ZHAO Hailing, SHEN Zhengri, WANG Chen, WANG Yun, QIU Xinping, LI Ping

2021, 26(1):  1-9.  doi:10.12092/j.issn.1009-2501.2021.01.001

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AIM: To observe the effect of Tangshen formula (TSF) treatment on TGF-β1/Smad3 pathway and cellular cholesterol efflux and explore its potential mechanism in HG-induced mouse tubular epithelial cells (mTECs). METHODS: After 25 mmol/L high glucose induced mTECs, TSF and Smad3 inhibitor SIS3 were given to intervene respectively. The lipid content in the cells was detected by ELISA kit; TGF-β1/Smad3 pathway and PGC-1α, LXR, ABCA1, ABCG1 were detected by Western blot and real-time PCR. RESULTS: TSF diminished the levels of TC, TG, LDL-C and increased the levels of HDL-C in HG-induced mTECs. Western blot and real-time PCR analysis showed that expression levels of TGF-β1, Smad3, Collagen Ⅰ and Fibronectin were significantly downregulated in the HG-induced mTECs with TSF and SIS3 treatment. And PGC-1α, LXR, ABCA1, ABCG1 expression levels were significantly upregulated in the HG-induced mTECs with TSF and SIS3 treatment. CONCLUSION: TSF can promote the cellular cholesterol efflux in HG-induced mTECs vis suppression of TGF-β1/Smad3 pathway. 

miR-34a inhibits proliferation of prostate cancer LNCaP cells by regulating androgen receptor gene

PENG Fusheng, HUANG Xiaohui, LI Peng, TANG Jian'er

2021, 26(1):  10-17.  doi:10.12092/j.issn.1009-2501.2021.01.002

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AIM: To explore the effect of microRNA-34a (miR-34a) on androgen receptor gene (AR) targeting regulation and proliferation and apoptosis of prostate cancer (PCa) LNCaP cells.  METHODS: Thirty-six patients with PCa confirmed by prostate biopsy in urology department of our hospital were collected from October 2016 to September 2019, and 41 cases of benign prostatic hyperplasia (BPH) tissue samples were taken and operated at the same time. LNCaP cells were cultured in vitro and transfected with miR-34a mimics (mimics group), miR-34a mimic NC (NC group) respectively, and normal growth cells were set as blank control group (BC group). In addition, on the basis of mimics group, the AR over-expression vector (AR over-expression group) and its control group (AR control group) were transfected. The cell activity was detected by CCK-8 kit, the apoptosis rate was detected by Annexin V-FITC/PI double staining flow cytometry test kit, the expression of miR-34a and AR mRNA was detected by real-time quantitative PCR (RT-qPCR), the expression of AR protein, CyclinD1, c-Myc and apoptosis-related proteins (Bcl-2, Bax, capase-3) was detected by Western blotting. RESULTS: Compared with BPH tissues, the expression of miR-34a in PCa tissues decreased significantly (P<0.05), and the expression of AR mRNA and protein increased significantly (P<0.05). Compared with BC and NC group, miR-34a expression level, apoptosis rate and Bax protein expression level of LNCaP cells in mimics group increased significantly (P<0.05), the expression levels of AR, Cyclin D1, c-Myc and Bcl-2 decreased significantly (P<0.05), the activity of LNCaP cells decreased significantly at the same time (P<0.05). The dual-luciferase assay showed that miR-34a may have a direct targeting relationship with AR. Over-expression of AR gene could reverse the inhibition of miR-34a mimics on LNCaP cell proliferation and promote apoptosis. CONCLUSION: miR-34a may inhibit the proliferation and promote the apoptosis of prostate cancer LNCaP cells by regulating AR gene.

Xintahua water extract improves the disease indexes of atherosclerosis model rats

GUAN Li, CHEN Wu, SUN Junfang, LI Wei

2021, 26(1):  18-23.  doi:10.12092/j.issn.1009-2501.2021.01.003

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AIM: To investigate the effect of water extract of Ziziphora clinopodioides Lam (WEZ) on improving atherosclerosis model rats. METHODS: Sixty SD rats were randomly selected and 50 rats of them were randomly selected for atherosclerosis model with high-fat emulsion and vitamin D3, and then randomly divided into atherosclerosis (AS) model group, low, medium, high WEZ group and the positive control group. After 8 weeks of drug intervention, the plasma of each group of rats was collected to detect total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and trimethylamine oxide (TMAO) level. The correlation between plasma TMAO and TNF-α and IL-6 levels in AS rats was detected. The aortic tissue-embedded sections of rats in each group were taken out to compare the aortic plaque area/aortic lumen area (PA/LA) ratio. RESULTS: Compared with the blank control group, the serum TC and TG levels of the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the serum TC and TG levels of the middle and high dose WEZ group and the positive control group were significantly decreased, and the difference was statistically significant (P<0.05). Compared with the blank control group, the serum TNF-α and IL-6 levels in the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the serum TNF-α and IL-6 levels of the high-dose WEZ group and the positive control group were significantly decreased, and the difference was statistically significant (P<0.05). Compared with the blank control group, the plasma TMAO level of rats in the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the plasma TMAO levels of rats in the high-dose WEZ group and the positive control group decreased significantly, and the difference was statistically significant (P<0.05). The analysis of the correlation between TMAO level and TNF-α/IL-6 level showed that TMAO level was positively correlated with TNF-α level (P=0.001, r=0.673), and positively correlated with IL-6 level (P=0.002, r= 0.646). Compared with the blank control group, the PA/LA ratio of the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the PA/LA ratio of rats in the medium and high dose WEZ group and the positive control group decreased significantly, and the difference was statistically significant (P<0.05). CONCLUSION: WEZ may regulate TMAO levels, down-regulate TNF-α and IL-6 levels, and reduces TC and TG levels, thereby improving AS, but its mechanism still needs further study.

Preparation and the effect of antitumor of DNA plasmid lipidosome vaccine based VEGFR2 extracellular region by immunization activated in vitro

CHEN Minfang, CHEN Lihua, XIE Liyun, XU Fenfen, XIA Aixiao, LIN Zhong

2021, 26(1):  24-29.  doi:10.12092/j.issn.1009-2501.2021.01.004

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AIM: The DNA plasmid lipidosome (LP) vaccine based VEGFR2 extracellular region (exVEGFR2) was prepared in order to provide a new approach for cancer active immunotherapy.  METHODS: High fidelity PCR was used to amplify the target sequence of exVEGFR2 with two restriction site of KpnⅠ and XbaⅠ. The plasmid of pCMV/exVEGFR2 was constructed by connected exVEGFR2 with pCMV empty plasmid. The activity of immune activation was detected by ELISA. CTLs mediated cytotoxic activity was analyzed by 51Cr release assay. RESULTS: The 90 000 target specific band of VEGFR2 was detected by Western blot. After 6 weeks since the first time vaccination, an intense specific immune response of anti-VEGFR2 was detected by ELISA in the serum from the C57BL/6 mouse vaccinated with LP-pCMV/exVEGFR2 vaccine. The T cells from the spleen of mouse immunized with the vaccine induced the cytotoxicity effect on CT-26 with VEGFR2 positive. CONCLUSION: The results of the specific immune response of anti-VEGFR2 in vivo and the antitumor cytotoxicity in vitro by vaccinated with LP-pCMV/exVEGFR2 vaccine in mouse model, would lay the foundation for further study of VEGFR2 positive tumor treated in vivo by the active immunotherapy.

Development of software for individualizing dosage regimens of vancomycin based on population pharmacokinetics models

GUO Xianzhong, LIN Rongfang, LIN Weiwei

2021, 26(1):  30-39.  doi:10.12092/j.issn.1009-2501.2021.01.005

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AIM: To develop software for individualizing dosage regimens of vancomycin (VCM) according to the established population pharmacokinetics (PPK) models.  METHODS: VCM dosing software was developed using MyEclipse, SQL Server, and JRE. The software developing schemes included requirement analysis, general design, detailed design, software coding, software test, software maintenance and software redevelopment. RESULTS: The developed software achieved the functions such as input and management of patient information, prediction of trough concentrations under various dosing regimens which could help initial dosage design, and prediction of trough concentrations more accurately based on therapeutic drug monitoring results and Bayesian method which could help dosage adjustment. The software was utilized in the interpretation of VCM serum concentration, pharmacists proposed the suggestions for adjusting dosage regimens. The rechecked serum concentrations all reached the expected target blood concentration range in the group of adopting advice. CONCLUSION: The new developed software based on our established PPK models can provide a useful tool in the clinical setting to facilitate the individualized therapy for the adult and elderly infected patients.

Analysis on genetic polymorphism of SLCO1B1 and ApoE in patients with cardiovascular diseases of Han nationality in Anhui area and its clinical significance for individualized use of statins

WANG Fengling, MENG Xiangyun, CHEN Zhengxu, CAO Rongjuan, HE Zhengmin, YE Xi, WANG Cong, LI Qi

2021, 26(1):  40-48.  doi:10.12092/j.issn.1009-2501.2021.01.006

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AIM: To investigate the polymorphism distribution of lipid and drug metabolism-related genes of SLCO1B1 and ApoE in patients with cardiovascular disease of Han nationality in Anhui province, and to evaluate the benefit-risk ratio of individual use of statins.  METHODS: PCR fluorescence probe technique was used to detect the genetic polymorphism of rs2306283 (388A>G) and rs4149056 (521T>C) of SLCO1B1 as well as rs429358 (388 T>C) and rs7412 (526C>T) of ApoE in 736 individuals diagnosed with cardiovascular diseases in the inpatient department of the Second People's Hospital of Hefei from January 2019 to August 2020 were included. The distribution characteristics of SLCO1B1 and ApoE genotypes were analyzed according to the gender of the subjects, and the results of genetic polymorphism were compared with the data of cardiovascular disease patients in other areas of China. RESULTS: Six genotypes of SLCO1B1 had been detected. They were *1a/*1a (6.11%), *1a/*1b (29.08%), *1b/*1b (44.57%), *1a/*15 (4.08%), *1b/*15 (15.49%) and *15/*15 (0.68%), while *1a/*5, *5/*5 and *5/*15 had not been detected. Six genotypes of ApoE had been detected. They were E2/E2 (0.41%), E2/E3 (11.96%), E2/E4 (1.09%), E3/E3 (67.66%), E3/E4 (17.93%) and E4/E4 (0.95%). The frequency distribution of genetic polymorphism of these two genes satisfied the Hardy-Weinberg genetic equilibrium, which was representative of the population. In this study, the proportion of people with SLCO1B1 normal myopathy risk was the highest, accounting for 79.76%; SLCO1B1 had a lower proportion of people with moderate myopathy risk and high myopathy risk were 19.57% and 0.68%, respectively. The reduced risk, normal risk and increased risk phenotypes of ApoE were respectively 12.37%, 68.75% and 18.88%. There was no statistically significant difference in SLCO1B1 and ApoE genotypes beween gender. Compared with patients with cardiovascular disease in Southern China area, the distribution of ApoE genetic polymorphism was significantly different in Anhui. CONCLUSION: The SLCO1B1 and ApoE genetic polymorphism of 736 patients with cardiovascular diseases in Anhui were mainly normal myopathy risk types with higher dose tolerance of statins as well as popular genotypes that were sensitive to statins, and the application of statins has a lower risk of myopathy and a good effect on lipid reduction. The polymorphism of the two genes was not affected by gender, but the distribution phenotypes of ApoE might be different in regional characteristics. The detection of SLCO1B1 and ApoE genetic polymorphism is significant for evaluation of benefit-risk ratios, thereby guiding statins clinical treatment. 

Research status of long non-coding RNA MALAT1 in breast cancer

SONG Dandan, CHEN Xueyuan, CHEN Ruiqi, LI Hanqiao, WU Tian

2021, 26(1):  49-57.  doi:10.12092/j.issn.1009-2501.2021.01.007

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Long non-coding RNA (LncRNA) is a kind of RNA longer than 200nt, whose abnormal expression plays a significant role in the development of tumors. Metastasis-associated lung adenocarcinoma transcription 1 (MALAT1), as one of LncRNAs, is closely related to the pathogenesis of breast cancer. MALAT1 can affect the tumorigenesis and progression of breast cancer and is expected to be an effective target for the diagnosis and treatment of breast cancer. Herein, we review the research status of MALAT1 in breast cancer.

Application of pharmacomicrobiomics in new drug development

ZHANG Yulong, ZHAO Ying, ZHANG Wei

2021, 26(1):  58-64.  doi:10.12092/j.issn.1009-2501.2021.01.008

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Pharmacogenomics promotes the success rate and efficiency of new drug development by targeting host genes. However, host gene level cannot fully explain the difference of drug efficacy among individuals. Pharmacomicrobiomics is an important extension of pharmacogenomics, which studies the effects of gut microbiome on drug safety and efficacy. At present, big data, Multinomial analysis, fecal bacteria transplantation, synthetic biology and other disciplines and technologies related to gut microbiome have been gradually applied in new drug development. This review introduces the current situation of new drug development and the interaction between gut microbiome and drugs, and summarizes the current research and development progress of gut microbiome related drugs.

Application of chitosan nanoparticle served as drug delivery system for cancer therapy#br#

SUN Rensong, ZHANG Jianbin, FANG Jiani, LYU Xia, TANG Zeyao, TIAN Yan

2021, 26(1):  65-75.  doi:10.12092/j.issn.1009-2501.2021.01.009

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Cancer is one of the malignant diseases threatening human. In recent years, nanotechnology is becoming the hope the cancer treatment, as it can take the drugs targeting to tumor sites, with enhanced efficacy and reduced toxicity. Chitosan is the only alkaline polysaccharide in nature with good biocompatibility and biodegradability. Moreover, chitosan has many reaction sites to make derivatives with different properties. Chitosan and its derivatives are widely used for drug delivery systems and tissue engineering scaffolds. Hence, they are valuable in the field of biomedicine. In this paper, the recent advances chitosan nanoparticles as drug delivery system for delivering anticancer drugs are reviewed, especially the advances of the preparation, passive targeting, active targeting, and stimuli-responsive drug delivery systems of chitosan nanoparticles. 

Relationship between circadian rhythm sleep-wake disorders and the development of malignant tumor

LI Jiayi, ZHANG Yimeng, WANG Chenxi, LI Jun, PAN Yan

2021, 26(1):  76-81.  doi:10.12092/j.issn.1009-2501.2021.01.010

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The circadian rhythm regulates many physiological processes of the human body. The circadian rhythm sleep-wake disorder refers to a type of disease caused by the mismatch of sleep-wake cycle and circadian rhythm. It affects the human body's cognitive function and metabolic processes. The circadian rhythm sleep-wake disorder also promotes the growth of malignant tumors, directly and indirectly,  by changing the expression of clock genes and inhibiting the secretion of melatonin. This article discusses circadian rhythm sleep-wake disorders; the subgroups it includes, the pathological state it causes, and the relationship between it and the development of malignant tumor. We hope to provide possible treatment measures for tumors affected by circadian sleep-wake disorders.

Research progress on the relationship between nuclear factor-κB in placenta and pregnancy complications

JIANG Weijie, HE Haibo, TANG Hongbo, HE Junyu

2021, 26(1):  82-87.  doi:10.12092/j.issn.1009-2501.2021.01.011

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Nuclear factor kappa B (NF-κB) is an important intracellular transcription factor, which regulates the expression of many genes including inflammation and apoptosis and is widely distributed in placenta. In this review, we introduced the relationship between placental NF-κB and pregnancy complications such as preeclampsia, HELLP syndromne and premature rupture of membranes. The role of placental NF-κB in the development of the pregnancy complications and the progress of the treatment of related diseases through the NF-κB pathway was summarized. This review will lay the foundation for the further study of placental related diseases and provide new ideas for the diagnosis and treatment of pregnancy complications.

Research advances of histone deacetylase 3 in cardiovascular diseases

CHEN Lifang, WANG Bo, WANG Weirong

2021, 26(1):  88-97.  doi:10.12092/j.issn.1009-2501.2021.01.012

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Histone deacetylases (HDACs) are a class of epigenetic modification enzymes and closely related to chromatin structure and gene transcriptional regulation. HDAC3 belongs to class I HDACs. It is reported that HDAC3 plays a key role in heart development. Recent studies find that HDAC3 plays an important regulatory role in cardiovascular diseases. This paper reviews the class I HDAC family HDAC3, focuses on its localization, enzyme activity and the research progress of HDAC3 in congenital heart disease, coronary atherosclerotic heart disease, cardiomyopathies, heart failure, and arrhythmias. This review may provide new drug target for the clinical treatment of cardiovascular diseases.

Development of quantitative analysis methods of Rituximab and it's biosimilar in biological samples

HOU Liping, YAN Yuyang, LI Li, YANG Jianbo, OUYANG Dongsheng

2021, 26(1):  98-104.  doi:10.12092/j.issn.1009-2501.2021.01.013

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Rituximab is the main monoclonal antibody for targeted therapy currently. With more rituximab biosimilars appearing and clinical evaluation need increasing, it is crucial to develop rapid and effective quantitative methods to determine the rituximab blood concentration in biological matrices for drug metabolism and pharmacokinetics (DMPK) analysis. This article reviewed the application of ligand binding method (LBA), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and emerging quantitative technology to detect the blood concentration of Rituximab, which may provide valuable information for the analysts and testers when developing quantitative methods for rituximab and its biosimilars.

Research progress of Osimertinib acquired resistance

PEI Qinghua, SUN Jianli

2021, 26(1):  105-112.  doi:10.12092/j.issn.1009-2501.2021.01.014

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Osimertinib, as a representative of the third generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has significant curative effect for EGFR T790M mutation type non-small cell lung cancer (NSCLC). But with the development of clinical research Osimertinib's resistance gradually appear. How to deal with the resistance is a problem that the clinical workers must focus on. This article will review the latest research progress of the mechanisms and the solutions of osimertinib acquired resistance.

Research progress of monoclonal antibodies in pharmacokinetic characteristics, analysis methods and method validation

ZHU Xueya, LI Zeyun, TIAN Xin, ZHANG Xiaojian

2021, 26(1):  113-120.  doi:10.12092/j.issn.1009-2501.2021.01.015

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In recent years, monoclonal antibodies (mAbs) have been developing rapidly and widely used in fields of tumor, immunity, blood and other systemic diseases. Global share of mAbs in prescription drug market had reached up to $ 140 billion, 15.3% by 2019. As macromolecule proteins, with special structures and physiological properties, mAbs have great differences in absorption, distribution, metabolism and excretion in vivo compared with small molecule drugs, including characteristics of relatively large molecular mass, high specificity and selectivity in target combination, non-linear pharmacokinetics, time dependence, long half-life and so on. Fully understanding of these special pharmacokinetic characteristics shall effectively guide analysis of mAbs. Meanwhile, the particularity and complexity of disposal mechanism in organisms greatly increase the difficulty of biological detection. As a result, it is necessary to establish exclusive, sensitive, accurate and repeatable quantification methods in biological samples. This article focuses on pharmacokinetic characteristics, main analytical methods, and methodology validation of quantification for mAbs in biological samples, expounding with comparisons of small molecular drugs, so as to prompt development of pharmacokinetic study of this kind of drugs.