1.Jiawei Chunze Decoction treats urinary retention after spinal cord injury in rats based on the regulation of endoplasmic reticulum stress apoptosis
Bochao ZHU ; Yanjie LI ; Hewei QIN ; Nannan ZHAO ; Haoyuan LIU ; Zhenhua XU ; Yupu WANG
Chinese Journal of Tissue Engineering Research 2025;29(2):371-378
BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.
2.Traditional Chinese medicine monomer in treatment of neuroinflammation after spinal cord injury:effects of nuclear transcription factor kappa B signaling pathway
Zhenhua XU ; Yanjie LI ; Hewei QIN ; Haoyuan LIU ; Bochao ZHU ; Yupu WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):590-598
BACKGROUND:Targeted therapy based on nuclear transcription factor kappa B signaling pathway to explore neuroinflammation is increasingly worth exploring,and the advantages of Chinese medicine such as many targets,wide range,rich mechanisms,and few side effects have great potential in the treatment of various diseases. OBJECTIVE:Based on the nuclear transcription factor kappa B signaling pathway,this paper systematically expounded and summarized the research progress of kaempferol,safflower yellow,baicalin,and triptolide in the treatment of neuroinflammation after spinal cord injury. METHODS:Search terms"spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids"were searched in CNKI and PubMed databases.Totally 67 articles were finally included. RESULTS AND CONCLUSION:(1)The role of nuclear transcription factor kappa B signaling pathway in the nervous system is complex and diverse,which can regulate neutrophils,microglia,astrocytes,and macrophages,and mediate the occurrence and development of inflammation after injury.(2)The effects of traditional Chinese medicine monomers such as baicalin on the degradation of nuclear transcription factor kappa B inhibitory protein,the inhibition of phosphorylation process by safflowerin on nuclear transcription factor kappa B signaling pathway,and the inhibition of kaempferol on nuclear transcription factor kappa B signaling pathway p65 nuclear translocation can reduce the impact of inflammatory response on the body,thereby promoting the recovery of neurological function.(3)The nuclear transcription factor kappa B signaling pathway can promote inflammation and immune cell migration and activation in the early stage of injury,and can promote the repair of injury site and the occurrence of fibrosis in the middle and late stages of injury.Appropriate activation of the nuclear transcription factor kappa B signaling pathway can promote the release of inflammatory factors,improve the antioxidant capacity of cells,and promote the activation of immune cells,but the over-activated nuclear transcription factor kappa B signaling pathway can easily lead to the occurrence and continuation of chronic inflammation and the inhibition of apoptosis.(4)Future research can further explore how to accurately regulate the activation level of nuclear transcription factor kappa B signaling pathway,how to achieve precise intervention for nervous system inflammation and injury,and can also focus on the preparation of traditional Chinese medicine monomers and the mechanism of action of traditional Chinese medicine monomers on signaling pathways,in order to provide more effective treatment strategies for the rehabilitation and functional recovery of neurological diseases.
3.Mechanistic of Modified Chunzetang in Treating Spinal Cord Injury-induced Urinary Retention in Rats Based on JNK/p38 MAPK Signaling Pathway
Yupu WANG ; Yanjie LI ; Hewei QIN ; Haoyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):30-38
ObjectiveTo investigate the effects of modified Chunzetang on urinary retention in rats with spinal cord injury (SCI) and the c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathway. MethodBefore modeling, 10 of the 70 female SD rats were randomly selected to assign to the blank group, and 10 to the sham group. The remaining 50 rats were used to prepare a SCI-induced urinary retention model using the spinal cord transection method. The model rats were randomly divided into model group, low-dose modified Chunzetang group, high-dose modified Chunzetang group, and inhibitor group. After modeling, the blank group, sham group, and inhibitor group were given 2 mL of saline by gavage. The high-dose and low-dose groups of modified Chunzetang were given modified Chunzetang at 28.8 g·kg-1 and 14.4 g·kg-1 by gavage, respectively. The inhibitor group was injected intraperitoneally with the JNK inhibitor SP600125 twice a week at a dose of 15 mg·kg-1. All rats were gavaged for a total of 28 days. Urodynamic and bladder muscle tension tests were conducted to evaluate bladder function. Hematoxylin-eosin (HE) staining was performed to observe the morphology of bladder smooth muscle tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of JNK, phosphorylated (p)-p38 MAPK, B cell lymphoma-2 (Bcl-2), and cysteinyl aspartate-specific proteinase-3 (Caspase-3). Western blot was used to detect the expression levels of p-JNK, p-p38 MAPK, ETS-like protein-1 (ELK-1), and activator protein-1 (AP1) in the detrusor muscle. Immunofluorescence was used to detect the expression levels of p-JNK, p-p38 MAPK, and AP1. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was conducted to measure cell apoptosis. ResultCompared with blank group and sham group, the model group showed a significant increase in maximum bladder capacity and bladder compliance, and a significant decrease in leak point pressure. The minimum contraction force was increased, and the contraction frequency was significantly decreased (P<0.01). The structure of bladder smooth muscle was disordered, with a large number of vacuolar cells, tissue edema, mononuclear cell infiltration, obvious hemorrhage, and a trend towards fibrosis in connective tissue. TUNEL positive cells increased significantly. The protein expression levels of p-JNK, p-p38 MAPK, AP1, and ELK-1 were significantly increased (P<0.01). Compared with model group, all intervention groups showed significant improvement in urodynamic and bladder muscle contraction tests. In the low-dose modified Chunzetang group, the levels of p-p38 MAPK and Caspase-3 was decreased (P<0.05,P<0.01). The levels of JNK, p-p38 MAPK and Caspase-3 in the high-dose group were significantly decreased (P<0.01), and the level of Bcl-2 was significantly increased (P<0.01). The expression levels of p-JNK, p-p38 MAPK, and AP1 proteins were significantly reduced (P<0.01), and ELK-1 protein expression was decreased (P<0.05). The positive rate of p-JNK and AP1 receptors was significantly decreased (P<0.01). The positive cell rate was significantly decreased (P<0.01). The high-dose modified Chunzetang group was positioned between the low-dose group and the inhibitor group, with no significant difference compared to the inhibitor group. ConclusionModified Chunzetang can improve urinary retention in SCI and enhance the contraction force of bladder smooth muscle. This effect is related to the inhibition of the JNK/p38 MAPK signaling pathway activation, thereby reducing apoptosis of bladder smooth muscle cells.
4.A 4-week mindfulness and white noise combined intervention trial on executive functioning in adults with attention deficit hyperactivity disorder
Lanshuang WANG ; Yupu ZHAO ; Jialiang FENG
Chinese Mental Health Journal 2024;38(11):955-960
Objective:To explore the improvement effect of combined intervention of mindfulness and white noise on executive function of adult patients with attention deficit hyperactivity disorder(ADHD).Methods:A total of 45 adult patients with ADHD were selected and randomly divided into a combined intervention group,a mindful-ness intervention group,and a non-intervention group.Both the combined intervention group and the mindfulness in-tervention group underwent mindfulness intervention,while the combined intervention group simultaneously in-tegrates white noise,the non-intervention group was not given any intervention measures.At baseline and after 4 weeks of intervention,N-back Task,Flanker task,More-odd Shifting Task,Iowa Gambling Task,and ADHD Rating Scale were used to measure working memory,inhibitory control,cognitive flexibility,emotional decision-making,and ADHD symptoms.Results:After 4 weeks of intervention,the accuracy rates of the inhibition control and cogni-tive flexibility tasks were higher in the combined intervention group than in the mindfulness intervention group,while the reaction times were lower(Ps<0.05).The accuracy rates of working memory,inhibition control,and cognitive flexibility tasks were higher in the combined intervention group and the mindfulness intervention group than in the non-intervention group,while the reaction times,emotional decision-making scores,total ADHD scores,and scores in all dimensions were lower in the combined intervention group and the mindfulness intervention group than in the non-intervention group(Ps<0.05).Conclusion:Mindfulness and white noise combined intervention has significant advantages in improving executive function and reducing ADHD symptoms of adult patients with ADHD.
5.Clinical observation of Tuina plus Chinese medication hot compress for lumbar muscle strain
Ji MA ; Fei GU ; Yupu ZHANG ; Xingwei CHEN ; Yumin LIU ; Zhengcai YU ; Cheng WANG ; Jue HONG
Journal of Acupuncture and Tuina Science 2024;22(5):387-392
Objective:To discuss the clinical efficacy of treating lumbar muscle strain(LMS)with Tuina(Chinese therapeutic massage)plus Chinese medication hot compress. Methods:A total of 147 LMS patients were randomized into a Tuina group,a Chinese medication hot compress group,and a combined group,each consisting of 49 cases.The Tuina group received Tuina treatment;the Chinese medication hot compress group received Chinese medication hot compress treatment;and the combined group received the forementioned two therapies alternately.The three groups of patients were assessed using the visual analog scale(VAS)and Oswestry disability index(ODI)before treatment and after 2 weeks of treatment.A 2-month follow-up was also conducted to observe the relapse rate. Results:The VAS and ODI scores dropped significantly after treatment in all three groups compared with their baseline(P<0.05),and the combined group surpassed the other two groups in comparing the ODI score(P<0.05).The 2-month follow-up showed that the combined group had the lowest relapse rate among the three groups(P<0.05). Conclusion:Compared to each therapy used alone,Tuina plus Chinese medication hot compress can relieve pain,improve daily living function,and reduce the short-term relapse rate better in treating LMS patients.
6.Optimization of drying methods of Compound Scutellaria baicalensis extract powder
Yupu HUANG ; Dazhang WU ; Yumei TANG ; Sen WANG ; Yu WANG
China Pharmacy 2022;33(22):2748-2752
OBJECTIVE To optimize the drying methods of Compound Scutellaria baicalensis extract powder. METHODS Compound S. baicalensis extract powder was prepared by atmospheric pressure drying, decompression drying and spray drying respectively, and high-performance liquid chromatography (HPLC) fingerprint of the extract powder was established. The physical fingerprint of the extract powder was established by 13 secondary indexes, such as particle size, particle size distribution and bulk density. HPLC fingerprints and physical fingerprints of 3 kinds of extract powders were compared by similarity evaluation method; through the conversion of the secondary indexes, five primary indexes of homogeneity, stacking, compressibility, fluidity and stability were calculated, and the physical properties of 3 kinds of extract powder were evaluated. The compressibility parameters of 3 kinds of extract powder such as index of parameter (IP), index of parametric profile (IPP) and index of good compression (IGC) were calculated by the secondary index to evaluate the compression formability of the powder. RESULTS The similarity means of HPLC fingerprint of the extract powder obtained by atmospheric pressure drying, decompression drying and spray drying were 0.74, 0.90 and 0.94, respectively, and the similarity means of physical fingerprint were 0.74, 0.83 and 0.92, respectively. The overall similarity of spray drying extract powder was higher. The results of physical fingerprint analysis showed that the physical properties of the extract powder obtained by different drying methods were different. The 3 kinds of extract powder showed poor stability but good stacking. The homogenity and compressibility of extract powder by spray drying and decompression drying were better than those by atmospheric pressure drying, but the fluidity was worse than that by atmospheric pressure drying. The results of further compression formability analysis showed that the IP of spray drying extract powder was 0.54, IPP was 5.23, IGG was 5.03, and the spray drying extract powder could be directly pressed after adding a small amount of lubricant. CONCLUSIONS There are differences in HPLC and physical fingerprints of Compound S. baicalensis extract powder obtained by different drying methods. The spray drying extract powder possesses better Δ 基金项目 四川省公益性科研院所基本科研项目 (No.2022- 4-720) overall quality, which is more suitable for the drying of *第一作者副主任药师。研究方向:临床药学、药事管理、药物研 Compound S. baicalensis extract powder. 究。E-mail:hyptotti@163.com
8.The role of macrophages in acute pancreatitis
Su YAN ; Yupu HONG ; Weixing WANG
Chinese Journal of Microbiology and Immunology 2020;40(9):720-726
Acute pancreatitis (AP) is a common and severe disease causing multiple organ dysfunction. With the deepening of research on AP pathogenesis, it has been found that macrophages play an important role in the initiation and progress of AP. The systemic innate macrophage populations, such as the pancreatic macrophages, Kupffer cells, peritoneal macrophages and pulmonary macrophages, can be activated by inflammatory mediators in different stages of pancreatitis, triggering inflammatory cascade reaction and systemic inflammatory response syndrome. This review focused on the recent progress in the role of macrophages in AP.
9.Role of Toll-like receptor 4 and NOD-like receptor 3 inflammasome in liver injury of acute necrotizing pancreatitis rats with obesity
Fangchao MEI ; Jia YU ; Yupu HONG ; Man LI ; Yu ZHOU ; Yundong YOU ; He XIA ; Hongzhong JIN ; Weixing WANG
Chinese Journal of Pancreatology 2019;19(4):284-290
Objective To investigate the role of Toll-like receptor 4 ( TLR4 ) and NOD-like receptor 3 (NLRP3)inflammasome in the liver injury of acute necrotizing pancreatitis (ANP) rat with obesity. Methods Twenty-four SD rats were randomly divided into normal group, ANP group, obesity group and obesity ANP group. The obesity rat model was established by continuously feeding high fat diet and the ANP model was induced by retrograde infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats were killed at 12 h after model establishment, and automatic biochemical immune analyzer were used for detecting serum AMY, LIP, ALT, AST, TG and TC. Pathological changes of pancreas and liver tissue samples were observed by miscroscopy and pathological score was recorded. The levels of MPO, CD68 , TLR4, NLRP3 and IL-1βin liver tissue were detected by immunofluorescence, and NF-κB and caspase-3 in liver tissue were detected by immunohistochemistry. Results The serum ALT and AST in obesity ANP group were significantly increased than those in ANP group (233. 00 ± 34. 44 U/L vs 102. 83 ± 8. 90 U/L,388. 00 ± 41. 60 U/L vs 282. 00 ± 21. 06 U/L);and liver pathologic score was also significantly higher than ANP group (6. 66 ± 1. 21 vs 3. 33 ± 1. 03);and CD68 + /TLR4 +, CD68 + /NLRP3 +, TLR4 + /NLRP3 +, MPO, NF-κB, IL-1β and caspase-3 level were all greatly higher in obesity ANP than those in ANP group, respectively (24. 16 ± 1. 47 vs 6. 66 ± 1. 21, 25. 00 ± 2. 60 vs 7. 00 ± 1. 41, 14. 16 ± 1. 47 vs 5. 50 ± 1. 04, 35. 33 ± 6. 88 vs 20. 83 ± 2. 48, 58. 80 ± 6. 75 vs 37. 63 ± 2. 96, 50. 00 ± 2. 36 vs 35. 00 ± 2. 82, 66. 00 ± 4. 04 vs 55. 00 ± 2. 60); and all the differences were statistically significant (all P<0. 05). Conclusions Liver injury was more severe in ANP rats with obesity, which may be related to the fact that obesity may enhance the activation of TLR4/NLRP3 signal pathway and result in the release of more inflammatory factors.
10.Experimental study on the mechanism of glycogen synthase kinase-3β inhibitor on acute kidney injury of acute necrotizing pancreatitis in rats
Kailiang ZHAO ; Xiaojia YANG ; Chen CHEN ; Liang ZHAO ; Fangchao MEI ; Yupu HONG ; Weixing WANG
Chinese Critical Care Medicine 2019;31(6):719-724
Objective To explore the protective mechanism of glycogen synthase kinase-3β(GSK-3β) inhibitor TDZD-8 on acute necrotizing pancreatitis (ANP) associated kidney injury in rats. Methods SPF male Wistar rats were randomly divided into four groups (n = 20): sham operation group (Sham group), ANP model group, TDZD-8 intervention group and TDZD-8 control group. The rat ANP model was prepared by retrograde injection of 5% sodium taurocholate into the bile duct; the same volume of normal saline was injected into the pancreatic duct of the Sham group. The TDZD-8 intervention group and the TDZD-8 control group were injected with GSK-3β inhibitor TDZD-8 (1 mL/kg) via the femoral vein 30 minutes before the model or sham operation; the ANP model group and the Sham group were injected equal volume of 10% dimethyl sulfoxide (DMSO). Rats in each group were sacrificed at 12 hours after operation to measure the serum amylase (AMY), blood lipase (LIPA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and to observe the pathological changes of pancreatic tissues and kidney tissues. Ultrastructural change of renal cells was analyzed by transmission electron microscopy. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were evaluated by enzyme linked immunosorbent assay (ELISA). The activation of nuclear factor-κB p65 (NF-κB p65) was evaluated by immunohistochemistry assay. The protein expressions of GSK-3β, phospho-GSK-3β (Ser 9), tumor necrosis factor -α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and interleukin-10 (IL-10) in the kidney were determined by Western Blot. Results Compared with the Sham group, the serum and inflammatory factors levels of the ANP model group were significantly increased, the pathological damage of the pancreas and kidney tissues were severe, the histopathological score was significantly increased, the expression of NF-κB p65 was enhanced in the nucleus of the kidney tissue, and the expressions of GSK-3β, TNF-α, ICAM-1 and iNOS were significantly enhanced, and the expressions of p-GSK-3β(Ser 9) and IL-10 were significantly attenuated. Compared with the ANP model group, TDZD-8 pretreatment significantly reduced serum and inflammatory factor levels in the ANP model group [AMY (kU/L): 5.60±0.30 vs. 10.07±0.34, LIPA (U/L): 1 111.0±110.8 vs. 2 375.0±51.1, SCr (μmol/L): 47.38±1.48 vs. 72.50±2.43, BUN (mmol/L): 17.6±1.0 vs. 26.0±1.0, IL-1β (ng/L):195.90±5.50 vs. 332.40±38.29, IL-6 (ng/L): 246.10±26.74 vs. 385.30±32.19, all P < 0.01]; pathological damage of pancreas and kidney tissue (histopathological score: 7.1±0.4 vs. 12.1±0.3, 301.2±7.5 vs. 433.5±13.8, both P < 0.01) and ultrastructural damage of renal cells were alleviated; the expression of NF-κB p65 in the nucleus was significantly decreased; the expression of p-GSK-3β(Ser 9) was significantly increased, and blocking GSK-3β activity could inhibit the expressions of TNF-α, ICAM-1, iNOS and increase the expression of IL-10, while the expression of GSK-3β in renal tissues was not statistically significant. There were no significant differences between the TDZD-8 control group and the Sham group. Conclusions Blockade of GSK-3βactivity by TDZD-8 exerts the protective effect against kidney injury by inhibiting the inflammation signaling pathway in ANP. It can alleviate histopathological and ultrastructural changes in kidney injury, which protection mechanism is mediated by NF-κB and its related inflammatory mediators.

Result Analysis
Print
Save
E-mail