1.A preliminary study of mechanosensitive channels Piezo 1 and Piezo 2 promoting neurogenic bladder fibrosis in young rats
Lei LYU ; Yanping ZHANG ; Qi LI ; Junkui WANG ; Shuai YANG ; Zhaokai ZHOU ; Shuai LI ; Yibo WEN ; Yakai LIU ; Guowei SI ; Xingchen LIU ; Jianguo WEN
Journal of Modern Urology 2025;30(4):343-349
Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects,so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method:sham operation group (sham),2-week nerve transection group (NB-2W),6-week nerve transection group (NB-6W),2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W),with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling,while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased,while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group,but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group,but higher than that in the sham group (P<0.05).Compared with the sham group,the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group,NB-P-2W group had lower bladder leakage point pressure (BLPP),but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group,NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that,with the extension of nerve transection time,bladder fibrosis gradually worsened,the bladder wall became rough and thickened,calculi were visible inside,and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups,and no hydronephrosis was observed in the upper urinary tract.In addition,Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos,Collagen Ⅰ and α-SMA than the sham group (P<0.01),while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis,but its mechanism needs further study.
2. Exploration of molecular mechanism of Selaginella moelledorffii Hieron. in treatment of laryngeal cancer based on network-based pharmacology, molecular docking techniques and experimental validation
Yuan-Yuan LI ; Xin-Zhou YANG ; Si-Si WANG ; Wen-Qi LIU ; Li KANG ; Xin-Zhou YANG ; Sefidkon FATEMEH
Chinese Pharmacological Bulletin 2024;40(2):352-362
Aim To explore the molecular mechanism of Selaginella moelledorffii Hieron. in the treatment of laryngeal cancer. Methods According to the relevant literature reports, the chemical constituents of S. moellendorffii were obtained, and the active ingredients were screened out through the SwissADME database, and the targets were screened through the PharmMapper database. The laryngeal cancer-related targets were collected by searching OMIM and other databases, and the Venny 2.1.0 online platform was used to obtain the intersection of the two. Protein interaction analysis of the potential targets was performed using the STRNG platform. GO functional analysis and KEGG pathway analysis was carried out using DAVID database. Visual networks were built with Cytoscape 3.8.0 software. Molecular docking was validated by SYBYL-X 2. 0 software. MTT method, Hoechst 33258 staining method and Western blotting were also used for validation. Results At the molecular level, a total of 110 active ingredients of S. moellendorffii and 82 drug targets were screened out, 1,608 targets related to laryngeal cancer, and intersection of 34 targets. GO analysis yielded 135 entries, and KEGG analysis yielded a total of 61 pathways. Molecular docking results showed that the 11 key active ingredients such as 2", 3"-dihydrooch-naflavone wood flavonoids and 4 core target proteins such as MAPK1 had 95. 5% of good docking activity. At the cellular level, SM-BFRE was screened for its strongest inhibitory effect on laryngeal cancer cell proliferation through MTT assay. Furthermore, Hoechst 33258 staining showed that the decrease in Hep-2 cell viability produced by SM-BFRE was related to cell apoptosis. Finally, Western blot verified that SM-BFRE inhibited PI3K/Akt/NF through inhibition- K B/COX-2 pathway to induce apoptosis in laryngeal cancer cells. Conclusions To sum up, it fully reflects the multicomponent, multi-target, and multi-channel synergistic effect of S. moellendorffii in the treatment of laryngeal cancer, and provides a theoretical reference for further elucidation of the mechanism of action of S. moellendorffii in the treatment of laryngeal cancer.
3.A new suberin from roots of Ephedra sinica Stapf
Bo-wen ZHANG ; Meng LI ; Xiao-lan WANG ; Ying YANG ; Shi-qi ZHOU ; Si-qi TAO ; Meng YANG ; Deng-hui ZHU ; Ya-tong XU ; Wei-sheng FENG ; Xiao-ke ZHENG
Acta Pharmaceutica Sinica 2024;59(3):661-666
Six compounds were isolated from the roots of
4.Exercise-induced Modulation of Ferroptosis: Potential Mechanisms for Improvement in Parkinson’s Disease
Dong-Lei LU ; Wen-Yu ZHANG ; Si-Jie TAN ; Feng-Ying YANG
Progress in Biochemistry and Biophysics 2024;51(11):2880-2896
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by muscle rigidity, resting tremor, and postural instability, which severely impair the quality of life in middle-aged and elderly individuals. PD’s pathogenesis is complex, involving oxidative stress, immune inflammation, and genetic factors. Despite extensive research, precise therapeutic targets for PD remain elusive, necessitating further investigation into its underlying mechanisms. Recent studies highlight the pivotal role of regional brain iron overload, oxidative stress, and lipid peroxidation in PD’s pathogenesis. Ferroptosis, a form of regulated cell death driven by iron dependency and lipid peroxidation, has emerged as a critical factor in PD pathology. This review examines the relationship between ferroptosis and PD and explores the potential of exercise as a therapeutic intervention to modulate ferroptosis and alleviate PD symptoms. Ferroptosis, distinct from other forms of cell death such as necrosis, autophagy, pyroptosis, and apoptosis, is characterized by mitochondrial shrinkage, reduced cristae, and membrane collapse, without nuclear fragmentation, DNA cleavage, or caspase activation. It is induced by the accumulation of intracellular Fe2+, which enhances lipid peroxidation and reactive oxygen species (ROS) generation, ultimately leading to cell death. Studies show disrupted iron metabolism in PD patients, with elevated iron levels in dopaminergic neurons of the substantia nigra correlating with disease severity. Iron chelation therapy has shown promise in alleviating PD symptoms by reducing brain iron levels, highlighting the significance of iron metabolism in PD pathogenesis. Lipid peroxidation, a hallmark of ferroptosis, involves the oxidation of polyunsaturated fatty acids (PUFAs) in cell membranes, compromising membrane integrity and increasing permeability. Elevated lipid peroxidation in the substantia nigra contributes to neuronal damage in PD. Enzymes such as ACSL4 and LPCAT3, crucial in PUFA metabolism, play significant roles in ferroptosis. Exercise has been shown to modulate these enzymes, potentially reducing lipid peroxidation and preventing ferroptosis in PD. Glutathione (GSH) metabolism is another crucial factor in ferroptosis regulation. GSH depletion impairs ROS detoxification, exacerbating oxidative stress and lipid peroxidation. PD patients exhibit reduced GSH levels in the substantia nigra, making dopaminergic neurons more vulnerable to oxidative damage. Exercise enhances GSH synthesis and activity, mitigating oxidative stress and ferroptosis in PD. α-Synuclein aggregation, a hallmark of PD, is closely linked to iron metabolism and oxidative stress. Excessive α‑synuclein binds to iron, promoting its aggregation and inducing ferroptosis. Exercise has been found to reduceα-synuclein accumulation and its pathological phosphorylation, potentially through the upregulation of neuroprotective proteins like DJ-1 and Irisin. These proteins enhance antioxidant defenses and facilitate α‑synuclein degradation, providing a protective effect against PD progression. Additionally, glutamate excitotoxicity, driven by dysregulated glutamate metabolism and receptor activity, contributes to ferroptosis in PD. Exercise modulates glutamate levels and receptor expression, reducing excitotoxicity and iron-induced neuronal damage. In conclusion, emerging research suggests that exercise may inhibit ferroptosis through multiple mechanisms, including regulation of iron metabolism, enhancement of antioxidant defenses, reduction of α-synuclein aggregation, and modulation of glutamate metabolism. These findings highlight the potential of exercise as a non-pharmacological intervention in the prevention and treatment of PD. Further research is needed to elucidate precise mechanisms and optimize exercise protocols for maximum therapeutic benefit.
5.Synthesis and activity evaluation of 6-azazindole derivatives for pancreatic cancer therapy
Yang CAO ; Qian LI ; Ya-ling WANG ; Wen-hui CUI ; Chen-liang QIAN ; Xin-xin SI
Acta Pharmaceutica Sinica 2024;59(10):2828-2835
Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC50 = 6.40 ± 0.34 μmol·L-1) and Ⅱ-2 (IC50 = 7.15 ± 0.51 μmol·L-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.
6.Research on species identification of commercial medicinal and food homology scented herbal tea
Jing SUN ; Zi-yi HUANG ; Si-qi LI ; Yu-fang LI ; Yan HU ; Shi-wen GUO ; Ge HU ; Chuan-pu SHEN ; Fu-rong YANG ; Yu-lin LIN ; Tian-yi XIN ; Xiang-dong PU
Acta Pharmaceutica Sinica 2024;59(9):2612-2624
The adulteration and counterfeiting of herbal ingredients in medicinal and food homology (MFH) have a serious impact on the quality of herbal materials, thereby endangering human health. Compared to pharmaceutical drugs, health products derived from traditional Chinese medicine (TCM) are more easily accessible and closely integrated into consumers' daily life. However, the authentication of the authenticity of TCM ingredients in MFH has not received sufficient attention. The lack of clear standards emphasizes the necessity of conducting systematic research in this area. This study utilized DNA barcoding technology, combining ITS2,
7.Chemical constituents from the leaves of Cyclocarya paliurus and their α-glucosidase inhibitory activities
Yong YANG ; Ting-Si GUO ; Min XIE ; Li-Hong TAN ; Wen-Chu LI ; Hao ZHENG ; Fei-Bing HUANG ; Yu-Pei YANG ; Wei WANG ; Yu-Qing JIAN
Chinese Traditional Patent Medicine 2024;46(3):834-842
AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.
8.Development and reliability and validity test of the Scale of Pain-Relevant Responses from Spouse for Chronic Pain Patients
Wen SI ; Qiao LIU ; Dandan SUO ; Qing YANG ; Na WANG
Chinese Journal of Practical Nursing 2024;40(3):174-180
Objective:To develop the Scale of Pain-Relevant Responses from Spouse for Chronic Pain Patients and to test its reliability and validity, so as to provide a reliable tool for the scientific assessment of the pain-relevant responses from spouses for chronic pain patients.Methods:Based on the interpersonal process model of intimacy, the first draft of the scale was formed through literature analysis, semi-structured interview, Delphi expert consultation and pre-investigation. A questionnaire survey was conducted on 388 patients with chronic pain who visited the Second Affiliated Hospital of Air Force Military Medical University from April 2022 to April 2023 using convenience sampling method to test the reliability and validity of the scale.Results:The Scale of Pain-Relevant Responses from Spouse for Chronic Pain Patients included 21 items in 4 dimensions: emotional support pain-relevant responses, behavioral support pain-relevant responses, distractive pain-relevant responses and negative pain-relevant responses. The range of I-CVI was 0.850-1.000. The results of structural validity analysis showed that four qualified common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 71.173%. The confirmatory factor analysis model fit indicators were within the acceptable range. The correlation validity coefficient was 0.692 ( P<0.01). The Cronbach α coefficient of the total table was 0.894, the half reliability was 0.906, and the retest reliability was 0.927. Conclusions:The Scale of Pain-Relevant Responses from Spouse for Chronic Pain Patients has good reliability and validity, and is suitable for the evaluation of pain-relevant responses from spouse of chronic pain patients.
9.Metabonomic study of blood of mice with high-voltage electrical injury
Si-Yu CHEN ; Hui WANG ; Yan LUO ; Jia-Wen TAO ; Wen-Juan ZHANG ; Yang YUE ; Zheng-Ping YU ; Hui-Feng PI
Journal of Regional Anatomy and Operative Surgery 2024;33(2):100-106
Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.
10.A new iridoid from Eucommia ulmoides
Shi-qi ZHOU ; Zhi-you HAO ; Meng YANG ; Chao-yuan XIAO ; Jun-yang ZHANG ; Bo-wen ZHANG ; Si-qi TAO ; Xiao-ke ZHENG ; Wei-sheng FENG
Acta Pharmaceutica Sinica 2024;59(7):2062-2068
Eleven compounds were isolated from

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