1.Effect of ERK1/2 on ischemic preconditioning in diabetic rat hearts
Caiyun MA ; Like ZHANG ; Fenghe DU ; Lingqiao LU ; Hongxia WANG ; Xiangjun ZENG ; Ping FU ; Qingqing MAN
Chinese Journal of Pathophysiology 1986;0(01):-
AIM: To test the effect of ERK1/2 on ischemic preconditioning (IPC) in diabetic rat hearts. METHODS: The diabetic rat model was made with alloxan. After eight weeks, 24 rats were divided into 4 groups: non-diabetic IPC rats (group A); non-diabetic non-IPC rats (group B); diabetic IPC rats (group C); diabetic non-IPC rats (group D). ECGⅡ lead, left ventricular development pressure (LVDP), and first derivative of LVDP ~(?dp/dt_~max ) were recorded. Myocardial phosphorylation of extracellular signal regulated kinases1/2 (ERK1/2) was detected by Western-blotting. RESULTS: (1) The ventricular arrythmia score was significantly lower in group A than that in group C (P
2.Methodological evaluation of rhCNB in long-tailed macaque sera detected by Enzyme-linked Immunosorbent Assay(ELISA)
Jiping SHAO ; Caiyun ZHANG ; Buwei HU ; Xueli XIE ; Shuhong TIAN ; Richao WANG ; Daolong HUANG ; Jian FU
Chinese Journal of Immunology 2016;32(4):528-531
Objective:To validate an enzyme linked immunosorbent assay (ELISA) method for the quantification of rhCNB in long-tailed macaque sera.Methods: The linear,sensitivity,accuracy,precision and recovery were determined using ELISA.Results:The present ELISA method had high linearity within 0.195 ng/ml-12.5 ng/ml,the working curve of rhCNB was Y=15.1X-0.26, R2=0.996 8 , the method showed good sensitivity of 0.195 ng/ml, the accuracy were in the range of 91.9%-108.8%, and the Coefficient of variation ( CV) for inter-assay were 3.55%,1.39%and 4.71%,the intra-assay were 1.59%,3.2%and 3.8%,all less than 10%, the recoveries were in the range of 88.5% -108.3%, <110% .Thus the method was coincidence with requirement.Conclusion:Double antibody sandwich ELISA assay of rhCNB in long-tailed macaque sera has good sensitivity ,accuracy, precision and recovery and it can be used to measure rhCNB concentration in biological samples .
3.Advances in the mouse models of myeloid leukemia.
Journal of Biomedical Engineering 2019;36(5):885-892
Mouse animal models are the most commonly used experimental tools in scientific research, which have been widely favored by researchers. The animal model of mouse leukemia appeared in the 1930s. During the past 90 years, researchers have developed various types of mouse leukemia models to simulate the development and treatment of human leukemia in order to promote effectively the elucidation of the molecular mechanism of leukemia' development and progression, as well as the development of targeted drugs for the treatment of leukemia. Considering that to myeloid leukemia, especially acute myeloid leukemia, there currently is no good clinical treatment, it is urgent to clarify its new molecular mechanism and develop new therapeutic targets. This review focuses on the various types of mouse models about myeloid leukemia used commonly in recent years, including mouse strains, myeloid leukemia cell types, and modeling methods, which are expected to provide a reference for relevant researchers to select animal models during myeloid leukemia research.
Animals
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Disease Models, Animal
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Humans
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Leukemia, Myeloid, Acute
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Mice
4.Advances in the research and application of neurokinin-1 receptor antagonists
HONG XIANGYU ; MA JUNJIE ; ZHENG SHANSHAN ; ZHAO GUANGYU ; FU CAIYUN
Journal of Zhejiang University. Science. B 2024;25(2):91-105
Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis.These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers,as well as the underlying mechanisms.Furthermore,the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized,such as solid dispersion systems,nanonization,and nanoencapsulation.As a radiopharmaceutical therapeutic,the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors.However,combining NK-1R antagonists with other drugs can produce a synergistic effect,thereby enhancing the therapeutic effect,alleviating the symptoms,and improving patients'quality of life in several diseases and cancers.
5.ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways
YAN ZHIBIN ; SHI YING ; YANG RUNLING ; XUE JIJUN ; FU CAIYUN
Journal of Zhejiang University. Science. B 2024;25(4):341-353
Kidney fibrosis is an inevitable result of various chronic kidney diseases(CKDs)and significantly contributes to end-stage renal failure.Currently,there is no specific treatment available for renal fibrosis.ELA13(amino acid sequence:RRCMPLHSRVPFP)is a conserved region of ELABELA in all vertebrates;however,its biological activity has been very little studied.In the present study,we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1(TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion(UUO)mice.Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum,and reduce the expression of fibrosis biomarkers confirmed by Masson staining,immunohistochemistry,real-time polymerase chain reaction(RT-PCR),and western blot.Inflammation biomarkers were increased after UUO and decreased by administration of ELA13.Furthermore,we found that the levels of essential molecules in the mothers against decapentaplegic(Smad)and extracellular signal-regulated kinase(ERK)pathways were reduced by ELA13 treatment in vivo and in vitro.In conclusion,ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.
6.Visualization analysis of research status and hotspots of Kaixin Powder based on VOSviewer and CiteSpace
Huilan ZHANG ; Ruoling WANG ; Jun WEN ; Peng HUANG ; Caiyun ZHANG ; Li FU
International Journal of Traditional Chinese Medicine 2024;46(4):506-513
Objective:To discuss the research status and hotspots of Kaixin Powder.Methods:Literature about Kaixin Powder was retrieved from CNKI, Wanfang Data, VIP, CBM, PubMed and Web of Science databases from the establishment of the databases to January 10, 2023. CiteSpace 6.2.R2 and VOSviewer 1.6.16 software were used to visualize and analyze data on the types of literature included, source journals, publication volume, authors, institutions, keywords, etc.Results:Totally 235 articles were included, mainly Chinese journal article. There were 87 source journals involved, among the Chinese and English journals, China Journal of Chinese Materia Medica and J Ethnopharmacol published the most articles. The overall annual number of articles published in the Kaixin Powder showed an upward trend. It involved 505 authors, forming research teams with Liu Ping, Jiang Yanyan and others as the core; The authors of the included literature came from 99 research institutions, and the cooperation between institutions was mainly based on units with the same or similar geographical area, TCM universities and their affiliated hospitals. The data results of keyword co-occurrence clustering network, keyword co-occurrence time network and keyword emergence analysis showed that the composition of the main active components (ginsenosides, poria acid, fine octyl ethers, ketones and oligosaccharide esters), detection methods (high performance liquid chromatography and liquid chromatography-mass chromatography), pharmacological effects (anti-Alzheimer's disease, antidepressant), mechanism of action and clinical application of the combination were the current research hotspots and trends in development. Conclusion:The research of Kaixin Powder mostly focuses on the mechanism of action and clinical research of Alzheimer's disease, depression and other diseases, among which the research on the main active components in Kaixin Powder is a hot topic in recent years, while the development trend of pharmacological mechanism of action and clinical application is better, and the correlation between active components and efficacy may become a new hot direction in the research of Kaixin Powder.
7.Analysis of loss to follow-up status and influencing factors of children born to pregnant women with HIV infection in China in 2019
Ya GAO ; Xiaoyan WANG ; Qun GAO ; Dongxu HUANG ; Qian WANG ; Yu WANG ; Hongqiao ZHENG ; Xinwei LI ; Caiyun FU ; Ziqi ZHANG ; Ailing WANG
Chinese Journal of Epidemiology 2024;45(6):833-838
Objective:To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019.Methods:The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results:The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (a OR=0.34, 95% CI: 0.22-0.53), unmarried (a OR=0.47, 95% CI: 0.24-0.93), first marriage (a OR=0.38, 95% CI: 0.22-0.67), remarriage (a OR=0.36, 95% CI: 0.20-0.67) and cohabiting (a OR=0.47, 95% CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (a OR=0.53, 95% CI: 0.40-0.70) was lower. Han nationality (a OR=1.52, 95% CI: 1.09-2.13), primary school (a OR=2.06, 95% CI: 1.10-3.89) and junior middle school (a OR=1.81, 95% CI: 1.03-3.17) educational level, non-use of antiviral drugs (a OR=6.21, 95% CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (a OR=5.72, 95% CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions:HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.
8.Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway
Yanxu CHEN ; Zhisheng JIN ; Xiaoxue JIANG ; Boling ZHANG ; Yaoqin FU ; Caiyun JIN ; Qinyuan ZHANG ; Changqing XU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):65-71
ObjectiveTo observe the effect of Hedysari Radix polysaccharide (HRP) on the Janus kinase 2 (JAK2)/signal transducer and activator of transcription protein 3 (STAT3) signaling pathway in diabetic nephropathy db/db mice. MethodFifty db/db mice were randomly divided into model group, irbesartan group (irbesartan suspension, 22.75 mg·kg-1), and high-, medium-, and low-dose HRP groups (HRP suspension, 200, 100, 50 mg·kg-1) according to the body weight, with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage, while those in the normal group and the model group received distilled water at 5 mL·kg-1. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid (UA), triglycerides (TG), and total cholesterol (TC) were detected. Periodic acid-Schiff (PAS) staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the protein and mRNA expression levels of JAK2, STAT3, suppressor of cytokine signaling 3 (SOCS3), and tumor necrosis factor-α (TNF-α) in the kidney. ResultAfter 12 weeks of treatment, compared with the normal group, the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA, TG, and TC levels (P<0.01). Compared with the model group, the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA, TG, and TC levels (P<0.05, P<0.01). Compared with the normal group, the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2, STAT3, and TNF-α protein and mRNA expression levels (P<0.01). Compared with the model group, the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2, STAT3, and TNF-α protein and mRNA expression levels (P<0.05, P<0.01). ConclusionHRP can alleviate renal damage in diabetic nephropathy to a certain extent, and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.
9.Mechanism of miRNA-related Signaling Pathway Against Diabetic Nephropathy and Intervention of Traditional Chinese Medicine: A Review
Xiaoxue JIANG ; Zhisheng JIN ; Caiyun JIN ; Yanxu CHEN ; Boling ZHANG ; Yaoqin FU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):228-235
Diabetic nephropathy (DN), as one of the common chronic microvascular complications of diabetes, has become the main cause of renal failure in end-stage renal disease in China, increasing the risks of renal dialysis and kidney transplantation in diabetes patients. It is the leading cause of death in people with diabetes. The latest research on DN has focused on the gene level. microRNAs (miRNAs) are a family of endogenous accessible short-chain non-coding RNA molecules. By acting on a particular target, they activate or inhibit its mediated signaling pathways and related molecules, playing an important role in the occurrence and development of DN. They have become microeconomic factors for the prevention and treatment of DN. Traditional Chinese medicine (TCM) has a long history in the diagnosis and treatment of DN and has unique advantages such as significant curative effect and few side effects. A large number of studies have proved that TCM can target miRNA to affect multiple signaling pathways, participate in the regulation of inflammatory response, pyroptosis, mesenchymal transdifferentiation, and other pathological changes, and delay the further development of DN. Therefore, this study discusses the biogenesis mechanism of miRNA and its action mechanism in disease-related signaling pathways based on TCM diagnosis and treatment approaches from the perspective of miRNA, and summarizes the effect of TCM targeting miRNA on the disease-related signaling pathways and on DN. Thus, this study is expected to provide a theoretical reference for exploring the progress of TCM intervention in DN from the perspective of genes.
10.Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway
Yanxu CHEN ; Caiyun JIN ; Zhisheng JIN ; Xiaoxue JIANG ; Boling ZHANG ; Yaoqin FU ; Liu HE
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):74-80
ObjectiveTo observe the effect of Hedysarum polysaccharides (HPS) on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy. MethodFifty db/db mice were randomly divided into model group, irbesartan group, and high, middle, and low-dose HPS experimental groups according to their body mass, with 10 mice in each group, and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg-1·d-1 distilled water, the irbesartan group was given 22.75 mg·kg-1·d-1 irbesartan suspension, and the high, middle, and low-dose HPS experimental groups were given 200, 100, and 50 mg·kg-1·d-1 HPS suspensions, respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state, blood glucose (GLU), 24 h urine protein (UTP), blood creatinine (SCr), and urea nitrogen (BUN) of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining (HE). The protein and mRNA expression levels of Wnt1, β-catenin, glycogen synthesis kinase-3β (GSK-3β), and phosphorylated GSK-3β (p-GSK-3β) in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultAfter treatment for 12 weeks, as compared with the normal group, the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU, 24 h UTP, SCr, and BUN in the model group increased (P<0.01). As compared with the model group, the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent, and the levels of SCr, BUN, and 24 h UTP in the high and middle-dose HPS groups decreased (P<0.05,P<0.01). As compared with the normal group, the expression levels of Wnt1, β-catenin, GSK-3β, and p-GSK-3β protein and mRNA in the model group were higher (P<0.01), while the expression levels of Wnt1, β-catenin, GSK-3β, and p-GSK-3β protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group (P<0.05,P<0.01). ConclusionHPS can alleviate the renal injury of diabetic nephropathy to some extent, and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.