1.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
2.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
3.Progress in the study of anti-inflammatory active components with anti-inflammatory effects and mechanisms in Caragana Fabr.
Yu-mei MA ; Ju-yuan LUO ; Tao CHEN ; Hong-mei LI ; Cheng SHEN ; Shuo WANG ; Zhi-bo SONG ; Yu-lin LI
Acta Pharmaceutica Sinica 2025;60(1):58-71
The plants of the genus
4.Role and mechanism of neuronal restriction silencing factor REST/NRSF in regulation of epilepsy
Hui LIU ; Bai-Hui YU ; Ya-Qi WANG ; Yi-Ling CHEN ; Zi-Hao CHENG ; Jia-Rui MA ; Zi-Shuo KANG ; Fan ZHANG
Chinese Pharmacological Bulletin 2024;40(9):1727-1734
Aim To investigate the effect and role of neuronal restriction silencing factor(REST/NRSF)in epilepsy disorder.Methods Immunohistochemistry,immunofluorescence,Western blot and qPCR tech-niques were used to detect REST/NRSF expression levels in hippocampal tissues of mice induced by kainic acid and human brain tissue.Viral injections,EEG re-cordings and behavioral methods were used to test the effects on epileptic mice after knockdown and overex-pression of REST/NRSF in the hippocampal CA1 re-gion,respectively.Results The positive rate of REST/NRSF in the lesions of epileptic patients was significantly higher compared with that in the control group.The levels of REST/NRSF protein and mRNA in the CA1 region of the hippocampus of mice in the KA model group were significantly higher.Kv7.2 and Kv7.3 potassium channel mRNA expression levels were significantly down-regulated.Significant up-regu-lation of REST/NRSF expression levels was observed in mouse hippocampus after NMDA injection.Knock-down of REST/NRSF in the CA1 region of hippocam-pus significantly elevated the expression levels of Kv7.2 and Kv7.3 potassium channel mRNAs.The fre-quency of EEG spiking and sharp-wave issuance and epileptic seizure grade were significantly lower.Over-expression of REST/NRSF in the CA1 region of hippo-campus significantly reduced the mRNA expression lev-els of Kv7.2 and Kv7.3 potassium channels.The fre-quency of EEG spiking and sharp-wave issuance was significantly higher and epileptic symptoms were exac-erbated.Conclusion REST/NRSF in mouse hipp-ocampal brain regions is involved in epileptic disease development through transcriptional regulation of Kv7.2 and Kv7.3 potassium channels.
5.Effect of binaural beat therapy on sleep structure in patients with post-stroke sleep disorders
Siyao GUO ; Shuo GAO ; Jie CHENG ; Ying YU
Chinese Journal of Modern Nursing 2024;30(32):4426-4432
Objective:To investigate the impact of binaural beat therapy (BBT) on the sleep structure of patients with post-stroke sleep disorders (PSSD) .Methods:Using convenience sampling, a total of 135 patients with PSSD who were admitted to the Department of Neurosurgery at the Affiliated Hospital of North China University of Science and Technology from October 2022 to October 2023 were selected and randomly divided into three groups: BBT group, regular music group, and control group, with 45 patients in each group. The control group received routine care, while the BBT group received binaural beat music training in addition to routine care, and the regular music group received regular music training along with routine care. Polysomnography data were recorded one day before the intervention and on the 28th day to compare sleep structure differences before and after the intervention in the three groups.Results:Eventually, 42 cases were completed in the control group, 43 cases in the regular music group, and 42 cases in the BBT group. After the intervention, there was no statistically significant difference in the percentage of non-rapid eye movement (NREM) sleep among the three groups ( P>0.05). The percentage of N2 sleep in all three groups was lower than before the intervention, and the BBT group had a lower percentage of N2 sleep than the regular music group and the control group. The percentage of N3 sleep in all three groups was higher than before the intervention, and the BBT group had a higher percentage of N3 sleep than the regular music group and the control group, these differences were statistically significant ( P<0.05). The latencies of NREM and rapid eye movement sleep, as well as the number of awakenings, were lower in all three groups compared to before the intervention, and the BBT group had lower values than the regular music group and the control group, these differences were also statistically significant ( P<0.05). The sleep efficiency of all three groups was higher than before the intervention, and the BBT group had higher sleep efficiency than the regular music group and the control group, with a statistically significant difference ( P<0.05) . Conclusions:BBT can effectively improve sleep structure and enhance sleep quality in patients with PSSD.
6.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
Objective:
This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines.
Methods:
Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud.
Results:
In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model.
Conclusion
In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.
7.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
Objective:
This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines.
Methods:
Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud.
Results:
In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model.
Conclusion
In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.
8.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
Objective:
This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines.
Methods:
Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud.
Results:
In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model.
Conclusion
In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.
9.Management and Control of Perioperative Hypertension
Shuo CHENG ; Han XIE ; Tengfei SHAO ; Simin ZHOU ; Weihong GE
Herald of Medicine 2024;43(9):1444-1450
Uncontrolled hypertension in the perioperative period may affect the hemodynamic stability of patients during surgery and thus affect the prognosis of patients.This increases the risk of other complications and death.For hypertensive patients undergoing surgery,it is necessary to weigh the pros and cons,and choose appropriate antihypertensive drugs to reduce the incidence of perioperative adverse events.There is no unified conclusion on perioperative blood pressure management in China.This paper systematically reviewed the perioperative blood pressure control objectives and drug use programs,including non-cardiac surgery,cardiac surgery,pregnancy,and pheochromocytoma.It provided a reference for the perioperative management of hypertensive patients.
10.Research Progress of Renal Transporters in Polymyxin-induced Nephrotoxicity
Simin ZHOU ; Xuemei LUO ; Shuo CHENG ; Weihong GE
Herald of Medicine 2024;43(9):1451-1456
Polymyxins are the first-line drugs used in multidrug resistance(MDR)Gram-negative infections.Polymyxin-induced nephrotoxicity is the major dose-limiting factor hindering its clinical use.It has been suggested that the mechanism of polymyxin-associated nephrotoxicity is related to its accumulation in the kidney upon extensive reabsorption from renal proximal tubular cells,and one or more renal transporters may mediate the process that polymyxins enter the renal tubular cells across cytomembrane.This review aimed to describe the roles of renal transporters in polymyxins reabsorption into the renal tubular cells and provide reference for reducing the nephrotoxicity of polymyxin.

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