1.Structure of myelin in the central nervous system and another possible driving force for its formation-myelin compaction.
Qi SHAO ; Simin CHEN ; Tian XU ; Yuyu SHI ; Zijin SUN ; Qingguo WANG ; Xueqian WANG ; Fafeng CHENG
Journal of Zhejiang University. Science. B 2025;26(4):303-316
Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism*
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Humans
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Central Nervous System/metabolism*
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Animals
2.Celastrol directly targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression.
Yuyu ZHU ; Lixin ZHAO ; Wei YAN ; Hongyue MA ; Wanjun ZHAO ; Jiao QU ; Wei ZHENG ; Chenyang ZHANG ; Haojie DU ; Meng YU ; Ning WAN ; Hui YE ; Yicheng XIE ; Bowen KE ; Qiang XU ; Haiyan SUN ; Yang SUN ; Zijun OUYANG
Acta Pharmaceutica Sinica B 2025;15(2):876-891
Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.
3.Erratum: Author correction to "Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice" Acta Pharm Sin B 11 (2021) 1200-1212.
Yuyu ZHU ; Ning WAN ; Xinni SHAN ; Guoliang DENG ; Qiang XU ; Hui YE ; Yang SUN
Acta Pharmaceutica Sinica B 2025;15(3):1719-1720
[This corrects the article DOI: 10.1016/j.apsb.2020.12.008.].
4.Erratum: Author correction to "SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade" Acta Pharm Sin B 9 (2019) 304-315.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2025;15(5):2810-2812
[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].
5.Discovery of toad-derived peptide analogue targeting ARF6 to induce immunogenic cell death for immunotherapy of hepatocellular carcinoma.
Dihui XU ; Xiang LV ; Meng YU ; Ao TAN ; Jiaojiao WANG ; Xinyi TANG ; Mengyuan LI ; Wenyuan WU ; Yuyu ZHU ; Jing ZHOU ; Hongyue MA
Journal of Pharmaceutical Analysis 2025;15(3):101038-101038
Image 1.
6.Efficacy and safety of CA280 cytokine adsorption column in treatment of acute-on-chronic liver failure
Yan HE ; Dakai GAN ; Xiaoqing ZHANG ; Tao LONG ; Xuezhen ZHANG ; Wei ZHANG ; Yizhen XU ; Yuyu ZENG ; Rui ZHOU ; Shuanglan LIU ; Xizi JIANG ; Yushi LU ; Molong XIONG ; Yunfeng XIONG
Journal of Clinical Hepatology 2025;41(10):2093-2101
ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange (LPE) in patients with acute-on-chronic liver failure (ACLF). MethodsA prospective cohort study was designed, and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment, the patients in the DPMAS+LPE group received DPMAS and LPE treatment, and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results, liver function parameters, renal function markers, electrolytes, coagulation function parameters, cytokines, adverse events, and 28-day prognosis before surgery (baseline), during surgery (DPMAS or CA280), and after surgery (after sequential LPE treatment). The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group, and the independent-samples t test was used for comparison between groups; the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group, and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups, and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment, the ACLF patients had significant reductions in the levels of cytokines (IL-6, IL-8, IL-10, TNF-α, and IFN-γ), liver function parameters (ALT, AST, ALP, TBil, DBil, Alb, and glutathione reductase), and the renal function marker urea nitrogen (all P<0.05), and in terms of coagulation function parameters, there were significant increases in prothrombin time, activated partial thromboplastin time (APTT), thrombin time, and international normalized ratio (INR) and significant reductions in prothrombin activity (PTA) and fibrinogen (FIB) (all P<0.05). Compared with the DPMAS+LPE group, the CA280+LPE group showed better improvements in the serum cytokines IL-8 (Z=-2.63, P=0.009), IL-10 (Z=-3.94, P<0.001), and TNF-α (Z=-1.53, P=0.023), and the two artificial liver support systems had a similar effect in improving liver function (ALT, AST, GGT, GR, TBil, and DBil) (all P >0.05), but the CA280+LPE group showed a significantly greater reduction in Alb (Z=-2.08, P=0.037). CA280+LPE was more effective in reducing uric acid (Z=-2.97, P=0.003). Compared with DPMAS+LPE, CA280+LPE treatment resulted in a significant reduction in INR (Z=-4.01, P<0.001), a significant increase in APTT (Z=-2.53, P=0.011), and significant greater increases in PTA (Z=-6.28, P<0.001) and FIB (Z=-3.93, P<0.001). There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups (all P>0.05). The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC (r=0.22, P=0.042), TBil (r=0.29, P=0.005), and FIB (r=-0.33, P=0.003); IL-8 was positively correlated with APTT (r=0.37, P<0.001) and INR (r=0.25, P=0.013); TNF-α was significantly correlated with WBC (r=0.40, P<0.001) and TBil (r=0.34, P<0.001). ConclusionCompared with DPMAS, CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients, but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients, but further studies are needed to verify its long-term efficacy.
7.Comparison of HPLC fingerprint and contents of four nucleoside components before and after processing of Succus bambusae pinella preparata
Linyu ZHENG ; Weihao ZHU ; Meimei LUO ; Chunmei MEI ; Weidong LI ; Lei XU ; Yuyu HUANG
China Pharmacy 2024;35(21):2590-2595
OBJECTIVE To investigate the changes in high performance liquid chromatography (HPLC) fingerprint spectra and nucleoside components between Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata, providing a reference for the quality evaluation of the latter. METHODS HPLC fingerprint was established for 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata following the Similarity Evaluation System of TCM Chromatographic Fingerprints (2012 Edition). Hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS- DA) were conducted on their common peaks. The contents of four nucleoside components, hypoxanthine, uridine, adenine, and guanosine, in both Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were determined. RESULTS The similarity between the fingerprints of the 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine, Succus bambusae pinella preparata, and their corresponding reference fingerprints ranged from 0.851 to 0.990. A total of 10 common peaks were obtained for both samples, and 4 components were identified as hypoxanthine, uridine, adenine, and guanosine. The results of HCA, PCA and OPLS-DA showed that the samples of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were clustered into separate categories, with OPLS-DA selecting 4 differential components between them, ranked by variable importance projection values as peak 8, peak 1, peak 6 (adenine) and peak 10. The content determination results showed that the average contents of hypoxanthine, uridine, adenine and guanosine in Succus bambusae pinella preparata declined by 15.90%, 12.00%, 26.04% and 22.18% compared to Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine, respectively, with statistically significant differences in the contents of hypoxanthine, adenine and guanosine (P<0.05 or P<0.01). CONCLUSIONS The established fingerprint and content determination methods are simple to operate and have good repeatability, which are suitable for qualitative and quantitative analysis of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata. The average contents of the four nucleoside components decreased after the processing of Succus bambusae pinella preparata.
8.Differences of clinical characteristics between temporal lobe epilepsy with bilateral hippocampal sclerosis and temporal lobe epilepsy with unilateral hippocampal sclerosis
Qi TAO ; Chenmin HE ; Jingjing QIU ; Yuyu YANG ; Sha XU ; Yi GUO ; Hong LI ; Yao DING ; Meiping DING ; Shuang WANG
Chinese Journal of Neuromedicine 2024;23(5):450-457
Objective:To compare the differences of clinical characteristics of temporal lobe epilepsy with bilateral hippocampal sclerosis (TLE-bHS) with those of temporal lobe epilepsy with unilateral hippocampal sclerosis (TLE-uHS).Methods:A retrospective analysis was performed. Forty-eight patients with confirmed TLE-bHS enrolled in Epilepsy Center, Department of Neurology, Second Affiliated Hospital, Medical School of Zhejiang University from January 2013 to January 2022 were chosen, and 101 patients with confirmed TLE-uHS admitted to our hospital at the same time period were selected as controls. Clinical data such as onset age, disease course, past medical history, seizure frequency, anti-seizure medications, video EEG and neuropsychological test results, and outcomes were analyzed.Results:Compared with the TLE-uHS group, the TLE-bHS group had higher male proportion, elder onset age, shorter disease course, higher seizure frequency, more types of past and currently used anti-seizure medications, lower proportion of autonomic nerve with aura, higher proportion of no aura at onset, higher proportion of slow head background movement in video EEG, and lower memory quotient, verbal memory scores and non-verbal memory scores, with significant differences ( P<0.05); the differences in ratio of past medical history and ratio of distributions of regions with interictal epileptiform abnormalities between the 2 groups were statistically significant ( P<0.05): the TLE-bHS group had significantly higher proportion of previous intracranial infection/encephalitis and higher ratio of bilateral temporal epileptiform abnormalities than the TLE-uHS group, while the TLE-uHS group had significantly higher proportion of patients with febrile convulsion history and higher ratio of unilateral temporal epileptiform abnormalities ( P<0.05). Only 10 patients (20.8%) in the TLE-bHS group received non-drug therapy, including anterior temporal lobectomy in 3 patients (Engel grading I in postoperative follow-up for 2 years), neuroregulatory therapy in 4, and ketogenic diet in 4; of the 55 patients (54.5%) in the TLE-uHS group who underwent anterior temporal lobectomy, 48 patients (87.3%) had Engel grading I, 1 patient (1.8%) had grading II, 4 (7.3%) had grading III, and 2 (3.6%) had grading IV after 2 years of follow-up. Conclusion:Differences in onset age, disease course, past medical history, seizure frequency, anti-seizure medications, and video EEG and neuropsychological test results can help to discriminate patients with TLE-bHS or with TLE-uHS.
9.Application of CBL combined with 3D printing teaching in clinical teaching of sacral tumors
Guofeng BAO ; Zhiming CUI ; Qinyu WANG ; Xing ZHANG ; Guanhua XU ; Yuyu SUN ; Xiaoqin HUANG ; Hong GAO ; Limin CHEN ; Tingting GU ; Haiyan HUANG ; Hong YE
Chinese Journal of Medical Education Research 2023;22(2):220-223
Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.
10.New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.
Yuyu ZHU ; Zijun OUYANG ; Haojie DU ; Meijing WANG ; Jiaojiao WANG ; Haiyan SUN ; Lingdong KONG ; Qiang XU ; Hongyue MA ; Yang SUN
Acta Pharmaceutica Sinica B 2022;12(11):4011-4039
Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

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