4.Analysis of Animal Model Construction Methods of Different Subtypes of Gastroesophageal Reflux Disease Based on Literature
Mi LYU ; Kaiyue HUANG ; Xiaokang WANG ; Yuqian WANG ; Xiyun QIAO ; Lin LYU ; Hui CHE ; Shan LIU ; Fengyun WANG
Journal of Traditional Chinese Medicine 2025;66(13):1386-1394
ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease (GERD) based on literature, providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis (RE), nonerosive reflux disease (NERD) and Barrett's esophagus (BE) model construction from January 1, 2014 to January 27, 2024, were retrieved from databases such as CNKI, Wanfang, VIP, Web of Science, and Pubmed. Information on animal strains, genders, modeling methods including disease-syndrome combination models, modeling cycles were extracted; for studies with model evaluation, the methods of model evaluation were also extracted; then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE (88/148, 59.46%) and NERD (9/14, 64.29%). For BE, C57BL/6 mice were most commonly used (11/20, 55.00%). Male animals (RE: 111/135, 82.22%; NERD: 11/14, 78.57%; BE: 10/12, 83.33%) were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer, gastric content reflux, or mixed reflux, among which forestomach ligation + incomplete pylorus ligation (42/158, 26.58%) was the most common modeling method; the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa, visceral hypersensitivity, and emotional problems, and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus (8/14, 57.14%) was the most common modeling method; the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux, and constructing interleukin 2-interleukin 1β transgenic mice (7/25, 28.00%) was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE, NERD, and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics (e.g., RE focusing on structural damage, NERD emphasizing visceral hypersensitivity). Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches (e.g., composite etiology simulation) and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.
5. Mechanism of ellagic acid improving cognitive dysfunction in APP/PS double transgenic mice based on PI3K/AKT/GSK-3β signaling pathway
Li-Li ZHONG ; Xin LU ; Ying YU ; Qin-Yan ZHAO ; Jing ZHANG ; Tong-Hui LIU ; Xue-Yan NI ; Li-Li ZHONG ; Yan-Ling CHE ; Dan WU ; Hong LIU
Chinese Pharmacological Bulletin 2024;40(1):90-98
Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg
6.Bioactive glass:different application forms and functions by adjusting preparation process and doping elements
Hua GAO ; Hui CHE ; Dan HU ; Yuefeng HAO
Chinese Journal of Tissue Engineering Research 2024;28(29):4726-4733
BACKGROUND:Bioactive glass is a multifunctional synthetic composite material that releases active ions slowly and exhibits certain biological activities after affinity with tissues.Their versatility stems from the versatility of their preparation processes and components,allowing them to be applied in different clinical scenarios. OBJECTIVE:To review the main application forms,application fields of bioactive glass,as well as the influence of doping different elements on its function. METHODS:A literature search was conducted across WanFang Medical Database,CNKI Database,PubMed Database,and Web of Science Database,using the search terms"bioactive glass,slow-release ions,bone tissue engineering,composite scaffold,tissue regeneration and repair,biomedical engineering"in Chinese and English.The timeframe was limited from 2000 to 2023.Finally,88 articles were included for review. RESULTS AND CONCLUSION:(1)In terms of application forms,bioactive glass can be fabricated as coatings,particles,bone cements,and scaffolds according to needs.Coatings have the potential to enhance the biological activity of implants,yet they are susceptible to instability as a result of degradation.Particles offer a viable solution for the repair of irregular bone defects;however,particles produced through traditional methods often possess limited functionality.Bone cement provides the benefits of minimal invasiveness and injectability,yet its application is restricted to smaller bone defects.Scaffolds exhibit excellent mechanical properties and are commonly used for larger-sized bone defects,yet they have limited toughness.(2)In terms of applications,bioactive glass can be used in a variety of tissue regeneration and repair and disease treatment fields,including dentistry,orthopedics,soft tissue engineering,and cancer.(3)In terms of element doping,the addition of specific elements to bioactive glass not only improves its mechanical properties but also endows it with special biological functions such as bioactivity,degradability,and antibacterial properties.(4)Biologically active glass is a versatile material that can be used in different forms and functions by adjusting the preparation process and element doping to meet various clinical needs in bone tissue engineering and is widely used in the field of biomedical engineering.
7.The Functional Role of SUMOylation in The Tumor Microenvironment
Pan-Pan ZHAO ; Jun-Xu YU ; Ya-Ning CHE ; Hui-Yi LIANG ; Chao HUANG
Progress in Biochemistry and Biophysics 2024;51(6):1256-1268
Tumors continue to be a major challenge in human survival that we have yet to overcome. Despite the variety of treatment options available, we have not yet found an effective method. As more and more research is conducted, attention has been turned to a new field for tumor treatment—the tumor microenvironment (TME). This is a dynamic and complex environment consisting of various matrix cells surrounding cancer cells, including surrounding immune cells, blood vessels, extracellular matrix, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules, and some specific cell types. Firstly, endothelial cells play a key role in tumor development and the immune system’s protection of tumor cells. Secondly, immune cells, such as macrophages, Treg cells, Th17 cells, are widely involved in various immune responses and activities in the human body, such as inflammation responses promoting survival carefully orchestrated by the tumor. Even though many studies have extensively researched the TME and found many research schemes, so far, no key effective method has been found to treat tumors by affecting the TME. The TME is a key interaction area between the host immune system and the tumor. Cells within the TME influence each other and interact with cancer cells to affect cancer cell invasion, tumor growth, and metastasis. This is a new direction for cancer treatment. In the complex environment of the TME, post-translational modifications (PTMs) of proteins have been proven to play an important role in the TME. PTMs are dynamic, strictly regulated changes to proteins that control their function by regulating their structure, spatial location, and interaction. Among PTMs, a reversible post-translational modification called SUMOylation is a common regulatory mechanism in cellular processes. It is a post-translational modification that targets lysine residues with a small ubiquitin-like modifier (SUMO) in a reversible post-translational modification manner. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis, and apoptosis, playing a pivotal role in the TME, such as DNA damage repair, tumor metastasis, and also participates in immune cell differentiation, activation, and inhibition of immune cells. On the other hand, SUMO or sentrin-specific protease (SENP) inhibitors can interfere with the SUMOylation process, thereby affecting many biological processes, including immune response, carcinogenesis, cell cycle progression, and cell apoptosis, etc. In summary, this review aims to introduce the dynamic modification of protein SUMOylation on various immune cells and the application of various inhibitors, thereby exploring its role in the TME. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs. In conclusion, the TME is a complex and dynamic environment that plays a crucial role in the development and progression of tumors. Understanding the intricate interactions within the TME and the role of PTMs, particularly SUMOylation, could provide valuable insights into the mechanisms of tumor development and potentially lead to the development of novel therapeutic strategies. The study of SUMOylation and its effects on various immune cells in the TME is an exciting and promising area of research that could significantly advance our understanding of tumor biology and potentially lead to the development of more effective treatments for cancer. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs.
8.Explorations about the correlation between biological changes of meninges in periodontitis mice and cognitive impairment via single-cell RNA sequencing
Yiting JIANG ; Lina XU ; Xuri ZHAO ; Hui SHEN ; Che QIU ; Zhiyan HE ; Wei ZHOU ; Zhongchen SONG
Chinese Journal of Stomatology 2024;59(6):595-603
Objective:To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing.Methods:Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results:Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] ( t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] ( t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] ( t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests ( t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) ( t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) ( t=3.88, P=0.005; t=3.02, P=0.017). Conclusions:The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.
9.Comparison of postoperative visual acuity between two TECNIS multifocal intraocular lenses with different collocations
Tong LI ; Fuqiang LI ; Songtian CHE ; Zhuoya LI ; Xiaomin HU ; Rong GUO ; Hui ZHANG
International Eye Science 2024;24(6):842-847
AIM: To investigate the effect of different lens combinations on visual acuity, visual quality and patient satisfaction by comparing mixed implantation of Tecnis Symfony ZXR00(ZXR00)and Tecnis ZMB00(ZMB00)lenses, bilateral implantation of ZMB00 lenses, and bilateral implantation of ZXR00 lenses.METHODS:This retrospective case-control study included 117 patients with cataracts(234 eyes)who underwent phacoemulsification combined with intraocular lens(IOLs)implantation from August 2020 to December 2021. The 3 groups included 36 patients(72 eyes)who underwent bilateral implantation of ZXR00(RR group), 37 patients(74 eyes)who underwent bilateral implantation of ZMB00(MM group), and 44 patients(88 eyes)who underwent implantation with a combination of ZXR00 and ZMB00(MR group). The uncorrected distance visual acuity(UDVA, 5 m), uncorrected intermediate visual acuity(UIVA, 80 cm), uncorrected near visual acuity(UNVA, 40 cm), corrected distance visual acuity(CDVA), defocus curve, stereopsis and VF-14 and QoV visual quality scale of the patients in the three groups were assessed at 3-month follow-up.RESULTS:Bilateral UNVA in the MM and MR group were significantly better than that in the RR group(P<0.05). Bilateral UIVA was the best in the RR group. There were no significant differences in bilateral UDVA, CDVA and stereopsis among the groups(P>0.05). Values for near-stereoscopic acuity at 40 cm were 107.27±80.53, 105.67±83.79, and 108.69±97.66(20-400)arcsec in the MR, MM, and RR groups, respectively(P>0.05). Satisfaction rates exceeded 90% in all groups.CONCLUSION:All groups achieved good distance, intermediate, and near visual acuity and near-stereoscopic vision postoperatively. Mixed implantation with ZXR00 and ZMB00 lenses achieved excellent full-range vision and resulted in high satisfaction. These results may aid in developing individualized clinical treatment plans.
10.Butein ameliorates sciatic nerve injury by activating SIRT1 and mediating the FOXO1/NF-κB signaling pathway
Journal of China Medical University 2024;53(2):102-107
Objective This study aimed to explore the effect and possible mechanism of SIRT1 activation induced by butein on sciatic nerve injury in rats.Methods A total of 30 rats were randomly divided into a sham operation group,a sciatic nerve injury group,and a butein group,with 10 rats in each group.BBB motor scores and sciatic nerve function index were detected on the modeling surgery day,the 7th day after surgery,and the 14th day after surgery.The pathological changes of the sciatic nerve in each group were observed by HE staining.The apoptosis of sciatic nerve cells in each group was detected by TdT-mediated dUTP nick end labeling(TUNEL).The expres-sion of BDNF,MBP,GAP-43,SIRT1,FOXO1,Keap1,and NF-κB in the sciatic nerve was detected by Western blotting.Results Butein improved the pathological injury of the sciatic nerve,reduced the apoptosis of sciatic nerve cells,increased BDNF,MBP,GAP-43,and SIRT1 expression,and decreased FOXO1,Keap1,and NF-κB expression in the sciatic nerve.Conclusion Butein can inhibit FOXO1/NF-κB signaling pathway activation by up-regulating SIRT1 expression in rats with sciatic nerve injury and then improve the sciatic nerve pathological injury in rats.

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