1.A novel feedback loop: CELF1/circ-CELF1/BRPF3/KAT7 in cardiac fibrosis.
Yuan JIANG ; Bowen ZHANG ; Bo ZHANG ; Xinhua SONG ; Xiangyu WANG ; Wei ZENG ; Liyang ZUO ; Xinqi LIU ; Zheng DONG ; Wenzheng CHENG ; Yang QIAO ; Saidi JIN ; Dongni JI ; Xiaofei GUO ; Rong ZHANG ; Xieyang GONG ; Lihua SUN ; Lina XUAN ; Berezhnova Tatjana ALEXANDROVNA ; Xiaoxiang GUAN ; Mingyu ZHANG ; Baofeng YANG ; Chaoqian XU
Acta Pharmaceutica Sinica B 2025;15(10):5192-5211
Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.
2.Mechanism of Hanchuan Zupa Granules in the treatment of Influenza A virus based on network pharmacology and molecular docking
Meng HAO ; Lu ZHAO ; Ya ZENG ; Bowen YU ; Zhihong JI ; Keao LI ; Xuan MA
International Journal of Traditional Chinese Medicine 2022;44(10):1157-1163
Objective:To explore the ingredients, targets, and mechanisms of Hanchuan Zupa Granules in the treatiment of Influenza A virus.Methods:By using Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP), GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGkb), Therapeutic target database (TTD) and DrugBank database to obtain relevant components and targets of Hanchuan Zupa Granules in the treatment of Influenza A virus; R software was used for the obtain of Hanchuan Zupa Granules -Influenza A virus intersection targets; Cytoscape software was applied for the construction of "Hanchuan Zupa Granules-component-target" network; Protein-protein interaction network (PPI) and topological analysis were constructed by STRING database and Cytoscape software. Intersection targets for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by R software; Auto Dock Tools were used for molecular docking.Results:All together 111 potential active ingredients, with corresponding 131 targetswere identified from Hanchuan Zupa Granules in the treatment of Influenza A virus. Quercetin, apigenin, luteolin, kaempferol, wogonin, etc. are included as core ingredients. STAT3, MAPK1, MAPK3, AKT1, JUN, etc. are included as core targets. Intersection targets were mainly enriched in 178 signal pathways such as IL-17 signal pathway, influenza A signal pathway, TNF signal pathway, etc; Molecular docking showed that core component had a good affinity with the target.Conclusion:Hanchuan Zupa Granules could play the role of anti-Influenza A virus with multi-component-multi-target-multi-pathway,characteristics, and this syudy provide a basis for future experimental research on its mechanism.
3. Case study of different types of telemedicine diagnostic projects
Tingting PENG ; Nan WANG ; Xiao AN ; Tian WEI ; Bowen XUAN ; Wen FENG
Chinese Journal of Hospital Administration 2020;36(1):45-49
Objective:
To compare the similarities and differences of four telemedicine diagnostic projects, for providing evidence-based policy-making advice for the development of telemedicine diagnostic projects in China.
Methods:
Four projects led by the government, close medical alliances, loose medical alliances and companies were selected from November 2018 to June 2019. Through semi-structured interviews with different leaders, the authors analyzed the characteristics, problems and difficulties of different projects from three dimensions of organizational system, working conditions and operational effects.
Results:
A total of 18 people were interviewed. Projects were different from each other in leaders, connection mechanism and effectiveness, participants and timeliness as well. The projects led by the government and close medical alliances had limited local participants with strong connection, clear but limited sources of diagnostic doctors and relatively large workload. While the projects led by loose medical alliances and companies had a wide range of participants, relatively weak connection efficiency and long response time.
Conclusions
Different types of telemedicine diagnostic projects have supplemented the manpower shortage of diagnosis physicians at primary medical institutions, introduced new service participants, as well as improved the medical service system.
4.Clinical study of post-stroke upper limb spasmodic hemiplegia treated withneedling technique and Bobath therapy.
Runjie SUN ; Liang TIAN ; Xiaoli FANG ; Xiaozheng DU ; Bowen ZHU ; Zhongyang SONG ; Xuan XU ; Xiaoguang QIN
Chinese Acupuncture & Moxibustion 2017;37(4):372-376
OBJECTIVETo compare the difference in the clinical efficacy on post-stroke upper limb spasmodic hemiplegia between the combined therapy ofneedling technique and Bobath technology and simple Bobath technology.
METHODSSixty patients were randomized into an observation group and a control group, 30 cases in each one. The usual medication of neurological internal medicine was used in the two groups. In the control group, Bobath facilitation technology was applied to the rehabilitation training. In the observation group, on the basis of the treatment as the control group,needling technique was used to stimulate Zhongfu (LU 1), Tianfu (LU 3), Chize (LU 5), Quchi (LI 11), Jianshi (PC 5) and Daling (PC 7). The treatment was given once a day; 5 treatments made one session and totally 4-week treatment was required in the two groups. The modified Ashworth scale, the modified Fugle-Meyer assessment (FMA) and the Barthel index (BI) were adopted to evaluate the muscular tension, the upper limb motor function and the activities of daily living (ADL) before and after treatment in the two groups. The clinical efficacy was compared between the two groups.
RESULTSCompared with those before treatment, the modified Ashworth scale, Fugl-Meyer score and BI score were all improved after treatment in the two groups (all<0.01). The results in the observation group were better than those in the control group (all<0.01). The total clinical effective rate was 93.3% (28/30) in the observation group and was 80.0% (24/30) in the control group. The efficacy in the observation group was better than that in the control group (<0.05).
CONCLUSIONSTheneedling technique combined with Bobath therapy achieve the superior efficacy on post-stroke upper limb spasmodic hemiplegia as compared with the simple application Bobath therapy. This combined treatment effectively relieve spasmodic state and improve the upper limb motor function and the activities of daily living.
5.Acupuncture mainly with " manipulation for amblyopia in children.
Zhongyang SONG ; Xiaoguang QIN ; Runjie SUN ; Xuan XU ; Bowen ZHU ; Yuchan CHEN
Chinese Acupuncture & Moxibustion 2017;37(11):1183-1186
OBJECTIVETo observe the effect difference between reinforcing-reducing manipulation and "" manipulation for amblyopia in children.
METHODSA total of 68 children patients with amblyopia were assigned into an observation group and a control group by random number table, 34 cases (68 eyes) in each one. In the observation group, reinforcing-reducing manipulation was used at Yuyao (EX-HN 4), Taiyang (EX-HN 5), Tongziliao (GB 1), Jingming (BL 1), Cuanzhu (BL 2), and Chengqi (ST 1); twirling-reinforcing method was applied at Ganshu (BL 18), Shenshu (BL 23), and Guangming (GB 37);""manipulation was applied at bilateral Fengchi (GB 20). The acupoints and manipulations in the control group were the same as those in the observation group, except Fengchi (GB 20) with reinforcing-reducing method. All the treatment was given for 4 courses, 5 times as a course and once a day. The vision improvement was observed half a year after treatment.
RESULTSThe effective rates for ametropic amblyopia in the observation and control groups were respectively 92.0% (23/25) and 70.4% (19/27); anisometropic amblyopia, 85.7% (18/21) and 55.0% (11/20); strabismic amblyopia, 66.7% (12/18) and 29.4% (5/17). The effect of each type in the observation group was better than that in the control group (all<0.05).
CONCLUSION""manipulation for amblyopia is superior to reinforcing-reducing method and can obviously improve the vision.
6.Osteopontin promotes chondrocyte proliferation in osteoarthritis
Wei JIANG ; Bowen LIN ; Xuan ZHANG ; Hua WANG ; Shuguang GAO ; Fangjie ZHANG
Chinese Journal of Tissue Engineering Research 2017;21(24):3773-3777
BACKGROUND:Osteopontin, a kind of extracellular matrix glycoprotein, has been found to participate in synthesis and catabolism of osteoarthritic chondrocyte extracellular matrix. However, the effect of osteopontin on the proliferation ability of osteoarthritic chondrocytes is little reported. OBJECTIVE:To investigate the effect of osteopontin on the chondrocyte proliferation in human knee osteoarthritis. METHODS: Cartilage samples were obtained from the patients with knee osteoarthritis undergoing knee arthroplasty at the Xiangya Hospital from January 2012 to June 2012. The chondrocytes were isolated and cultured, and then divided into four groups: blank control, osteopontin, Con-shRNA and osteopontin-shRNA groups. The cell proliferation was detected by MTT and BrdU assays. RESULTS AND CONCLUSION: After transfection of osteopontin-shRNA lentivirus, the infection rate was up to 80%. Compared with the blank control group, osteopontin group showed a significant increase in the absorbance value of osteoarthritic chondrocytes, while after osteopontin-shRNA lentivirus transfection, the absorbance value was significantly decreased (bothP < 0.05). Additionally, after osteopontin-shRNA transfection, the expression level of osteopontin was significantly downregulated (P < 0.05). To conclude, osteopontin can promote the proliferation of osteoarthritic chondrocytes, which is considered as a new treatment target for osteoarthritis.

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