1.Application and mechanism of induced pluripotent stem cells in inherited heart disease models
Yangguang MA ; Yayong ZHANG ; Mingyao MENG ; Zhihao JIN ; Yingming LI ; Yaoxuan HUANG ; Shen HAN ; Yaxiong LI
Chinese Journal of Tissue Engineering Research 2024;28(25):4072-4078
BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.
2.Arthroscopic treatment of borderline developmental dysplasia of the hip with labral tear: analysis of mid-term outcomes
Ziyuan LI ; Gaolong SHI ; Zhigao JIN ; Zhihao CHEN ; Zhuoyan LING ; Jun GU ; Zonggang XIE
Chinese Journal of Orthopaedic Trauma 2023;25(11):959-964
Objective:To investigate the clinical efficacy of arthroscopic limited incision of the articular capsule to repair the glenoid labrum in the treatment of borderline developmental dysplasia of the hip (BDDH) complicated with labral tear.Methods:A retrospective study was conducted to analyze the data of 18 patients with BDDH complicated with labral tear who had been admitted to Department of Orthopaedics, The Second Hospital Affiliated to Suzhou University from January 2016 to December 2019 (observation group). There were 12 males and 6 females with an age of (41.8 ± 8.5) years. Simultaneously, another 18 patients were selected as the control group whose hip development was normal but age and gender were matched with those in the observation group. There were 9 males and 9 females with an age of (43.5 ± 10.3) years. Both groups were treated by arthroscopic limited incision of the articular capsule to repair the glenoid labrum. The 2 groups were compared in terms of modified Harris hip score (MHHS), Hip Outcome Score Activities of Daily Living Subscale (HOS-ADL), and visual analogue scale (VAS).Results:There was no significant difference in the demographic data like age, gender ratio, body mass index, severity of labral tear or time from injury to operation between the 2 groups, indicating comparability between groups ( P>0.05). The observation and control groups were followed up for (38 ± 7) and (43 ± 6) months, respectively. For the observation and control groups, respectively, MHHS was (97.1 ± 3.3) points and (95.4 ± 4.2) points, HOS-ADL (92.6 ± 2.8) points and (91.4 ± 4.1) points, and VAS (0.6 ± 0.5) points and (1.0 ± 0.8) points, all showing no significant difference between groups ( P>0.05). Conclusion:In the treatment of BDDH patients complicated with labral tear, simple arthroscopic limited incision of the articular capsule to repair the glenoid labrum can lead to the same good medium-term efficacy as it can in those with normal hip development.
3.Histological study of platelet-rich fibrin combined with MTA for direct pulp capping of rabbit teeth
YANG Xue ; YAN Zhihao ; LIU Jin ; HU Yuping ; LI Shufang
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(3):171-178
Objective :
To investigate the outcomes of a novel direct pulp capping agent containing platelet-rich fibrin (PRF) and mineral trioxide aggregate (MTA).
Methods :
A total of 32 New Zealand rabbits were randomly divided into 4 groups, namely, the PRF+MTA group (P+M group), PRF group (P group), MTA group (M group) and blank control group (BC group), with 8 rabbits per group. Dental pulp exposure and direct pulp capping were performed, and complete crown square sealing was performed on 2 mandibular central incisor teeth of each rabbit. Four rabbits from each group were euthanized after each observation period (7 and 28 days). The experimental teeth were subjected to HE staining. Inflammatory cell infiltration, calcified bridge formation and pulp tissue disorganization were observed and graded.
Results:
Inflammatory cell infiltration: on the 7th day, group P+M and group M were lighter than group BC (P<0.05); on the 28th day, group P+M was lighter than group P and group BC (P<0.05); group P+M and group M did not significantly differ (P>0.05). Calcified bridge formation: on the 7th and 28th days, group P+M was lighter than group P, group M and group BC (P<0.05); on the 28th day, group M was higher than group BC (P<0.05). Under microscope, the calcified bridge contained cellular components and was surrounded by odontoblast-like cells, sharing a structure resembled osteodentin; dentin tubule-like structure could not be observed in calcified bridge, and the calcified bridge resembled certain points of osteodentin. Pulp tissue disorganization: on the 7th day, group P+M and group M were lighter than group BC (P<0.05); on the 28th day, group P+M was lighter than group P and group BC (P<0.05). group P+M and group M did not significantly differ (P>0.05).
Conclusion
The combination of PRF and MTA for direct pulp capping provided light inflammatory cell infiltration, stable pulp status and a strong ability of pulp tissue to form calcified bridge, and the calcified bridge resembled certain points of osteodentin.
4.Research progress on the mechanism of Chinese medicine and active components against cartilage destruction of rheumatoid arthritis
Zhihao DUAN ; You ZHOU ; Shigang LI ; Can JIN ; Ying DENG ; Jinlang LIU ; Shuai MA
China Pharmacy 2023;34(7):892-896
Rheumatoid arthritis (RA) is a systemic chronic auto-inflammatory disease, characterized by infiltration of inflammatory cells, pannus formation, articular cartilage destruction, and bone matrix destruction. Therefore, improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components, multiple targets, high activity and low side effects. Based on this, the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors, phosphatidylinositol 3-kinase/protein kinase B, Wnt/β- catenin, nuclear factor-κB, mitogen-activated protein kinase, Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor, microRNAs, fibroblastic synovial cells.
5.The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis.
Tengjie YU ; Zhihao ZHOU ; Shijia LIU ; Changjian LI ; Zhi-Wei ZHANG ; Yong ZHANG ; Wei JIN ; Keanqi LIU ; Shuying MAO ; Lei ZHU ; Lin XIE ; Guangji WANG ; Yan LIANG
Acta Pharmaceutica Sinica B 2023;13(3):1231-1245
Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.
6.The osteoprotective effects and mechanisms of RA model mice by total saponins of Chaenomeles speciosa
Ying DENG ; Can JIN ; Zhihao DUAN ; Xiaoli ZHANG ; Shigang LI
China Pharmacy 2023;34(9):1042-1047
OBJECTIVE To study the osteoprotective effects and possible mechanism of total saponins of Chaenomeles speciosa on rheumatoid arthritis (RA) model mice, and to provide reference for further development of anti-RA drugs. METHODS Seventy male DBA/1 mice were randomly divided into normal group, model group, low-dose and high-dose groups of C. speciose total saponins (60, 240 mg/kg), Tripterygium wilfordii polyglycoside tablets group (positive control, 30 mg/kg), with 14 mice in each group. In addition to the normal group, the other groups of mice were induced by glucose-6-phosphate isomerase mixed polypeptide to prepare RA model. The body weight, rear toes thickness and arthritis scores of each group were recorded; the synovial inflammation, bone and cartilage destruction of ankle joint tissues were observed by hematoxylin-eosin staining, tartrate- resistant acid phosphatase staining and safranin O-fast green staining; the contents of interleukin-6 (IL-6) in serum and tumor necrosis factor α (TNF-α), IL-4 and IL-10 in ankle joint tissues were detected by ELISA; the expression levels of receptor activator of nuclear factor-κB ligand (RANKL), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), tumor necrosis factor receptor-associated protein 6 (TRAF6) and nuclear factor of activated T cells 1 (NFATC1) protein in ankle joint tissues were detected by Western blot assay. RESULTS At the end of administration, compared with normal group, the body mass of mice in the model group was significantly reduced (P<0.05), and the arthritis score and the thickness of the left and right rear toes were significantly increased (P<0.05); the ankle joint tissues of mice in the model group showed significant synovial proliferation and inflammatory infiltration, the number of osteoclasts increased significantly and significant destruction of cartilage tissue. The content of IL-6 in serum, the content of TNF-α, the protein expression levels of RANKL, RANK, TRAF6 and NFATC1 in the ankle joint tissues were increased significantly (P<0.05), while the contents of IL- 4 and IL-10, the protein expression level of OPG in the ankle joint tissues were decreased significantly (P<0.05). Compared with model group, above pathomorphological changes and the content/level of indicators of mice in each administration group were significantly improved (P<0.05). CONCLUSIONS Total saponins of C. speciosa may exert osteoprotective effects on RA model mice, the mechanism of which may be associated with reducing the contents of IL-6 and TNF-α, increasing the contents of IL-4 and IL-10, inhibiting the activation of RANKL/RANK/OPG signal pathway, thus inhibiting the proliferation of osteoclasts and promoting the repair of cartilage and bone tissue.
7. Oral lienal peptides improve ammonia-induced coughing and inflammation in mice
Shuying MAO ; Wei JIN ; Sisi FU ; Keanqi LIU ; Zhihao ZHOU ; Guangji WANG ; Yan LIANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(6):601-607
To study the effect of oral lienal polypeptide on cough and inflammation in mice, in order to expand the clinical application of immune modulator lienal polypeptide and provide a new strategy for relieving cough and inflammation. METHODS: The cough model of mice was induced by concentrated ammonia. The cough frequency and tolerance latency of mice within 6 minutes were recorded every day. The histopathological changes of spleen and lung were evaluated by HE staining and spleen index. TNF-α, IL-1β and IL-6 levels in spleen and lung of mice was detected by ELISA. RESULTS: Oral administration of spleen polypeptide could prolong the tolerance latency of mice to concentrated ammonia to a certain extent and significantly reduce the cough frequency of mice. HE staining showed that oral spleen polypeptide could significantly reduce the alveolar surface area and improve lung expansion in mice. The results of ELISA showed that oral spleen polypeptide decreased the levels of some proinflammatory factors in spleen and lung. CONCLUSION: Lienal polypeptide can alleviate cough and emphysema like symptoms induced by ammonia, improve immune ability and inflammation in mice.
8.Specific PCR Identification of Artemisia absinthium, A New Foreign Medicinal Resource of Artemisia
Zhihao LIU ; Ziyuan CHEN ; Xiaolin LI ; Chao JIANG ; Yan JIN ; Yuyang ZHAO ; Yuan YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(17):127-132
ObjectiveTo establish a specific polymerase chain reaction (PCR) method for the identification of Artemisia absinthium to allow accurate and convenient identification of A. absinthium and its related species. MethodThe chloroplast genome sequences of A. absinthium and its related species were searched from Chloroplast Genome Information Resource (CGIR), and the specific single nucleotide polymorphism (SNP) sites of A. absinthium were screened out. A pair of specific identification primers (zykh1-F and zykh1-R) of A. absinthium was designed. The original plant samples of A. absinthium and its related species were collected. The specific PCR method was established and optimized, and the tolerance and feasibility of this method were investigated and verified. The method was used to identify A. absinthium samples purchased from Xinjiang medicinal materials market. ResultA 210 bp bright band was obtained from A. absinthium after PCR amplification and gel electrophoresis under the following conditions: specific primers zykh1-F and zykh1-R, annealing temperature of 54 ℃, and the number of cycles of 33. No such band was observed from its relative species, such as A. argyi, A. annua, A. leucophylla, and A. lavandulaefolia. ConclusionThe specific PCR identification method of established in this study can accurately identify A. absinthium and its common related species with high specificity. The method can save time and cost and allows a convenient and fast species identification for the introduction and utilization of A. absinthium resources.
9.PSO+: nonlinear fitting fluorescence data based on particle swarm optimizing combine with other iteration algorithm.
Da FU ; Youbing CHEN ; Zhihao ZHUO ; Xiaoping MIN ; Hai WANG ; Shengxiang GE ; Shiyin ZHANG ; Jin WANG
Journal of Biomedical Engineering 2019;36(3):414-420
The convective polymerase chain reaction (CCPCR) uses the principle of thermal convection to allow the reagent to flow in the test tube and achieve the purpose of amplification by the temperature difference between the upper and lower portions of the test tube. In order to detect the amplification effect in real time, we added a fluorophore to the reagent system to reflect the amplification in real time through the intensity of fluorescence. The experimental results show that the fluorescence curve conforms to the S-type trend of the amplification curve, but there is a certain jitter condition due to the instability of the thermal convection, which is not conducive to the calculation of the cycle threshold (CT value). In order to solve this problem, this paper uses the dynamic method, using the double S-type function model to fit the curve, so that the fluorescence curve is smooth and the initial concentration of the nucleic acid can be deduced better to achieve the quantitative purpose based on the curve. At the same time, the PSO+ algorithm is used to solve the double s-type function parameters, that is, particle swarm optimization (PSO) algorithm combined with Levenberg-Marquardt, Newton-CG and other algorithms for curve fitting. The proposed method effectively overcoms PSO randomness and the shortcoming of traditional algorithms such as Levenberg-Marquardt and Newton-CG which are easy to fall into the local optimal solution. The of the data fitting result can reach 0.999 8. This study is of guiding significance for the future quantitative detection of real-time fluorescent heat convection amplification.
Algorithms
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Fluorescence
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Fluorescent Dyes
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Polymerase Chain Reaction
10.Effects of Glycyrrhizic Acid on Pharmacokinetics of Nifedipine in Rats
Jun MAO ; Xiangyu ZHU ; Hongguang XIA ; Zhihao WANG ; Huiru LIU ; Haiyan JIANG ; Yong JIN
China Pharmacy 2019;30(21):2942-2945
OBJECTIVE: To study the effects of glycyrrhizic acid on the pharmacokinetics of nifedipine in rats. METHODS: Rats were randomly divided into experimental group and control group, with 10 rats in each group. Experimental group was given glycyrrhizic acid 5 mg/kg and control group was given 0.5% CMC-Na (sodium carboxymethylcellulose) solution, once a day, for 14 consecutive days. On 14th day after 30 min of intragastric administration, both groups were given nifedipine 3 mg/kg intragastrically. Blood samples 0.5 mL were collected from intraocular vein plexus before and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h after intragastric administration. The concentration of nifedipine was determined by HPLC using diazepam as internal standard. The determination was performed on ODS-C18 column with mobile phase consisted of methanol-water (62 ∶ 38, V/V,pH adjusted to 4.5 with acetic acid) at the flow rate of 1.0 mL/min. The column temperature was 30 ℃. The detection wavelength was set at 238 nm, and sample size was 20 μL. The pharmacokinetic parameters were calculated with Winonlin 6.0 software, and statistical analysis was performed by t-test. RESULTS: The main pharmacokinetic parameters of the experimental group and the control group were as follows as tmax was (1.40±0.15), (1.50±0.01) h; cmax was (0.15±0.03), (0.29±0.09) mg/L; t1/2 was (4.70±1.17), (5.20±1.38) h; AUC0-24 h were (1.00±0.10), (1.89±0.37) mg·h/L; AUC0-∞ was (1.00±0.16), (1.98±0.32) mg·h/L; MRT was (6.76±0.64), (6.60±1.36) h, respectively. Compared with control group, cmax, AUC0-24 h and AUC0-∞ of nifedipine were decreased significantly in experimental group, with statistical significance (P<0.05). CONCLUSIONS: Glycyrrhizic acid can reduce the bioavailability of nifedipine in rats. It is suggested that the dosage of nifedipine should be increased in order to achieve effective blood concentration.


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