1.Monotropein improves motor function of mice with spinal cord injury by inhibiting the PI3K/AKT signaling pathway to suppress neuronal apoptosis.
Yue CHEN ; Linyu XIAO ; Lü REN ; Xue SONG ; Jing LI ; Jianguo HU
Journal of Southern Medical University 2025;45(4):774-784
OBJECTIVES:
To investigate the effect of monotropein on motor function recovery of mice with spinal cord injury (SCI) and explore the underlying mechanism.
METHODS:
Forty-five adult female C57BL/6 mice were randomized equally into sham operation group, SCI group, and SCI group with daily intraperitoneal monotropein injection. The mice in the former two groups received daily saline injections. Motor function of the mice was evaluated using BMS scores, slant plate test, and footprint analyses. Pathological changes and neuronal counts in the spinal cord were observed using HE, LFB, and Nissl staining. The biological functions of monotropein were explored using GO and KEGG enrichment analyses. NeuN/cleaved caspase-3 immunofluorescence assay and Western blotting were used to detect neuronal apoptosis in the spinal cord of the mice. In cultured HT22 cells, the effect of monotropein on TNF-α-induced cell apoptosis was evaluated using TUNEL staining and Western blotting. In monotropein-treated HT22 cells and SCI mice, the changes in the PI3K/AKT pathway were examined, and the effect of a PI3K/AKT pathway activator (IGF-1) on HT22 cell apoptosis and motor function recovery of SCI mice were observed.
RESULTS:
SCI mice with monotropein treatment showed significantly improved motor functions with reduced SCI areas and increased myelin retention and neuron counts in the spinal cord. Bioinformatics analysis suggested a role of PI3K/AKT signaling pathway in mediating the anti-apoptotic effects of monotropein. In SCI mice, monotropein obviously reduced apoptotic neurons, decreased expressions of cleaved caspase-3 and Bax and increased Bcl-2 expression in the spinal cord. In HT22 cells, monotropein significantly inhibited TNF-α-induced apoptosis and PI3K/AKT pathway activation. Treatment with IGF-1 obviously increased apoptosis of HT22 cells and exacerbated locomotor dysfunction in SCI mice.
CONCLUSIONS
Monotropein promotes motor function recovery in SCI mice by reducing neuronal apoptosis possibly by inhibiting the PI3K/AKT signaling pathway.
Animals
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Spinal Cord Injuries/metabolism*
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Apoptosis/drug effects*
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Signal Transduction/drug effects*
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Mice, Inbred C57BL
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Mice
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Proto-Oncogene Proteins c-akt/metabolism*
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Female
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Phosphatidylinositol 3-Kinases/metabolism*
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Neurons/pathology*
;
Recovery of Function
2.Ménétrier's Disease:Report of One Case and Literature Review.
Ming-Yue LÜ ; Su-Su LI ; Xin-Hua ZHANG
Acta Academiae Medicinae Sinicae 2025;47(5):762-767
Ménétrier's disease (MD) is a relatively rare special type of gastritis in clinical practice.This article reports the multiple diagnosis and treatment processes of a patient with MD in the northwest plateau region,reviews relevant literature,and summarizes the ultrasonic features of gastrointestinal contrast-enhanced ultrasound in this case and their value in the diagnosis and treatment process.Furthermore,this article discusses the key points of imaging differentiation of MD from chronic hypertrophic gastritis,multiple gastric polyps,gastric cancer,and gastric lymphoma.
Humans
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Gastritis, Hypertrophic/diagnosis*
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Ultrasonography
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Male
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Middle Aged
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Female
3.Protective effects of Silybum thistle extract and related formulations on liver in mice with alcoholism
Ting-Qiao WANG ; Wu-Jiang REN ; Liang-Yu LÜ ; Rong WEI ; Yue-Yi GUO ; Jian ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(7):1009-1013
Objective To investigate the protective effect of silymarin extract(SME)and its complex preparation on ethanol liver injury.Methods An ethanol liver injury model was established by gavage of 12 mL·kg-1 50%ethanol.Male mice were divided into blank group(distilled water),model group(ethanol liver injury model),SME-L,-H groups(6,20 mg·mL-1 SME),SME+Ganoderma lucidum extract(GLE)-L,-H groups(10,30 mg·mL-1 SME+GLE,SME∶GLE=1∶1),Jian An Shi Silymarin Pueraria Mirifica and Tansy tablets(JAS)-L,-H groups(68,204 mg·mL-1 JAS),there were 12 mice in each group.The serum levels of glutamic-oxaloacetic transaminase(GOT)in mice were measured by fully automated biochemical analyzer assay;the serum levels of interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in mice were measured by enzyme-linked immunosorbent assay(ELASA);the hepatic tissue of oxidative stress indexes[catalase(CAT)and total superoxide dismutase(T-SOD)]were measured by ultraviolet spectrophotometer.Results The T-SOD activity in the blank group,model group,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were(192.54±49.00),(141.65±34.72),(205.83±32.77),(191.68±25.83),(192.31±28.79),(177.82±32.61),(218.58±74.80)and(210.24±31.65)U·mg·prot-1;CAT activity were(37.78±5.73),(28.92±8.44),(44.12±11.52),(41.41±9.15),(47.01±10.48),(41.63±8.95),(47.14±8.91)and(48.29±10.06)U·mg-1;GPT levels were(47.61±13.00),(97.84±26.00),(62.33±18.92),(51.84±17.91),(70.77±28.00),(58.00±21.27),(52.28±18.78)and(45.55±9.27)U·L-1;IL-6 levels were(21.03±1.52),(28.43±5.75),(21.90±3.24),(21.23±1.55),(22.26±2.58),(21.24±2.91),(22.17±4.14)and(21.14±3.02)pg·mL-1.Comparing the above indexes in the model group with the blank group,and comparing the above indexes in the SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L,JAS-H groups with the model group,the differences were statistically significant(all P<0.01).The TNF-α levels in blank,model,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were were(28.07±7.72),(69.02±16.34),(40.29±8.94),(48.84±10.17),(41.91±14.96),(40.07±12.75),(50.72±11.44)and(45.05±11.34)pg·mL-1.Comparing the model group with the blank group,the SME,SME+GLE-L,-M and JAS,-M groups with the model group,the differences were statistically significant(all P<0.01).Conclusion Silybum marianum extract and its compound preparation can increase the antioxidant level and reduce the inflammation of mouse liver,and have a certain improvement effect on liver injury caused by acute ethanol poisoning.
4.Effects of Shiquan Dabu Decoction on cognitive impairment in a mouse model of Alzheimer's disease through regulation of synaptic function
Zi-He GUO ; Yi WANG ; Meng-Yao ZHU ; Hai-Yang YUAN ; Xin LÜ ; Yue-Song GONG
Chinese Traditional Patent Medicine 2024;46(1):72-78
AIM To explore the effects of Shiquan Dabu Decoction on the synaptic function and cognitive impairment in a mouse model of Alzheimer's disease(AD).METHODS Sixty mice were randomly divided into the control group,the model group,the memantine group(5 mg/kg)and the high,medium and low dose Shiquan Dabu Decoction groups(6.24,3.12 and 1.56 g/kg),with 10 mice in each group.Except for those of the control group,the mice of other groups underwent their 70-day AD models induction by intraperitoneal injection of D-galactose and gavage feeding of AlCl3,followed by 42-day corresponding dosing of drugs by gavage on the 29th day.The mice had their spatial learning and associative memory detected by Morris water maze test and conditioned fear test;their morphological changes of hippocampal neurons observed by HE staining;their serum SOD activity,MDA level,and SOD,AChE activities and MDA,ACh,TNF-α and IL-1β levels in hippocampus detected by kits;and their PSD-95,Shank3,NR1,NR2A,NR2B,AMPK and p-AMPK protein expressions in hippocampus detected by Western blot.RESULTS Compared with the model group,the high-dose Shiquan Dabu Decoction group displayed improved spatial learning and memory ability and associative memory(P<0.05,P<0.01);reduced pathological damage of hippocampal neurons,decreased levels of oxidative stress and inflammation(P<0.05,P<0.01);enhanced cholinergic transmission(P<0.05,P<0.01),and increased protein expressions of PSD-95,Shank3,NR1,NR2A,NR2B,and p-AMPK in hippocampal tissue(P<0.05,P<0.01).CONCLUSION Shiquan Dabu Decoction can improve the cognitive impairment of in the mouse model of AD,and its mechanism may be related to AMPK activation and synaptic function restoration.
5.Comparison of initial percutaneous balloon compression versus radiofrequency thermocoagulation followed by percutaneous balloon compression in the treatment of trigeminal neuralgia
Honghao ZHANG ; Zongbin JIANG ; Jing LÜ ; Peng ZHAO ; Kan YUE ; Ruilin HE
Journal of Central South University(Medical Sciences) 2024;49(1):40-46
Objective:There are a variety of minimally invasive interventional treatments for trigeminal neuralgia,and the efficacy evaluation is different.The preferred treatment scheme is still controversial.This study aims to investigate the differences in treatment effects between patients with primary trigeminal neuralgia(PTN)treated with percutaneous balloon compression(PBC)for the first intervention and patients with pain recurrence after radiofrequency thermocoagulation(RT)who then received PBC for PTN,and to offer clinicians and patients more scientifically grounded and precise treatment alternatives. Methods:We retrospectively analyzed 103 patients with PTN admitted to the Department of Pain Management of the Second Affiliated Hospital of Guangxi Medical University from January 2020 to December 2021,including 49 patients who received PBC for the first time(PBC group)and 54 patients who received PBC for pain recurrence after RT(RT+PBC group).General information,preoperative pain score,intraoperative oval foramen morphology,oval foramen area,balloon volume,duration of compression,and postoperative pain scores and pain recurrence at each time point on day 1(T1),day 7(T2),day 14(T3),1 month(T4),3 months(T5),and 1 year(T6)were collected and recorded for both groups.The differences in treatment effect,complications and recurrence between the 2 groups were compared,and the related influencing factors were analyzed. Results:The differences of general information,preoperative pain scores,foramen ovale morphology,foramen ovale area,T1 to T3 pain scores between the 2 groups were not statistically different(all P>0.05).The balloon filling volume in the PBC group was smaller than that in the RT+PBC group,the pain scores at T4 to T6 and pain recurrence were better than those in the RT+PBC group(all P<0.05).Pain recurrence was positively correlated with pain scores of T2 to T6(r=0.306,0.482,0.831,0.876,0.887,respectively;all P<0.01). Conclusion:The choice of PBC for the first intervention in PTN patients is superior to the choice of PBC after pain recurrence after RT treatment in terms of treatment outcome and pain recurrence.
6.Factor analysis of pain after arthroscopic rotator cuff suture bridge
Li-Na SI ; Jin-Wei LUO ; Di WU ; Yue-Bing QIAO ; Yong-Ming LÜ ; Cong XU
Acta Anatomica Sinica 2024;55(2):210-214
Objective To analyze the factors associated with pain after arthroscopic rotator cuff bridge suture.Methods According to the inclusion and exclusion criteria,the data of 112 patients with unilateral rotator cuff injury who received arthroscopic bridge suture in our department were collected and were investigated in the form of telephone follow-up.In this study,SPSS 23.0 was used to input data and conduct statistical analysis.Logistic regression analysis was used to analyze the correlation between the above influencing factors and postoperative pain.Results A total of 112 patients were included for statistical analysis,single factor analysis revealed,including course of disease,smoking history,preoperative University of California,Los Angeles(UCLA)score,Constant score,numeric rating scale(NRS),size of rotator cuff tear,whether it was full-thickness tear and degree of tendon retraction might be related to postoperative pain(P<0.05).The age,gender,body mass index(BMI),drinking history,diabetes and hypertension were not related to postoperative pain(P>0.05).Multiple linear regression analysis concluded that there were four factors related to postoperative pain,and the correlation degree was preoperative NRS,preoperative UCLA score,tear size and smoking history.Conclusion The causes of postoperative pain after arthroscopic rotator cauff repair are complex and diverse.Analyzing the cause of postoperative pain can effectively reduce the pain of patients and promote the recovery of shoulder joint function.
7.Jisuikang formula promotes spinal cord injury repair in rats by activating the YAP/PKM2 signaling axis in astrocytes
Hao MAN ; Jianwei WANG ; Mao WU ; Yang SHAO ; Junfeng YANG ; Shaoshuo LI ; Jinye LÜ ; Yue ZHOU
Journal of Southern Medical University 2024;44(4):636-643
Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.
8.Value of MRI-DWI combined with attenuation imaging in diagnosis of focal nodular lesions<2 cm in fatty liver
Yue LÜ ; Hujing LU ; Juanjuan ZHANG
The Journal of Practical Medicine 2024;40(15):2148-2153
Objective To investigate the value of magnetic resonance image-diffusion weighted imaging(MRI-DMI)combined with attenuation imaging(ATI)in the diagnosis of focal nodular lesions<2 cm in the back-ground of fatty liver.Methods The clinical data of 68 patients with fatty liver complicated with focal nodular lesions<2 cm were retrospectively analyzed from June 2022 to June 2023 in Huaihe Hospital of Henan University.All patients underwent MRI,pathology and ATI examination.According to the degree of fatty liver disease,68 patients were divided into severe group(n=24),moderate group(n=27)and mild group(n=17).The apparent diffusion coefficient(ADC)and acoustic attenuation coefficient(AC)values of patients with different focal lesions were compared with clinical data,and the ADC values and AC values of patients with different fatty liver lesions were compared with clinical data,and the correlation was analyzed by Pearson.To analyze the value of MRI-DWI combined with AC value in the diagnosis of malignant fatty liver disease with focal nodular disease<2 cm.Results Pathological diagnosis showed that 41 of the 68 patients were benign and 27 were malignant.There were no significant differences in low density lipoprotein cholesterol(LDL-C),age,triglyceride(TG),sex,total cholesterol(TC)and high density lipoprotein cholesterol(HDL-C)between benign nodule group and malignant nodule group(P>0.05).There was no difference in TG,age,HDL-C,sex,TC and LDL-C among mild,moderate and severe groups(P>0.05).The ADC value of malignant nodule group was lower than benign nodule group under different b values(P<0.05),and the AC value of malignant nodule group was higher than that of benign nodule group(P<0.05).ADC value under different b values in the severe group was lower than mild and moderate groups(P<0.05),ADC value under different b values in the moderate group was lower than mild group(P<0.05),AC value in the severe group was higher than mild and moderate groups(P<0.05),and AC value in the moderate group was higher than mild group(P<0.05).ADC values at different b values were negatively correlated with the degree of fatty liver disease(P<0.05),but not with TG,HDL-C,TC and LDL-C(P>0.05).AC was positively correlated with the degree of fatty liver disease(P<0.05),negatively correlated with HDL-C(P<0.05),but not with TG,TC and LDL-C(P>0.05).The area under the curve(AUC)values of MRI-DWI,AC and their combi-nation in the diagnosis of fatty liver complicated with focal nodule disease<2 cm into malignancy were 0.775,0.773 and 0.909,respectively(P<0.05),and the AUC value of the combination was higher(P<0.05).Conclusion MRI-DWI and ATI have important value in the differential diagnosis of benign and malignant lesions of focal nodular lesions<2 cm in the background of fatty liver,and the combination of MRI-DWI and ATI has higher diagnostic value.
9.Preliminary serum pharmacological exploration of method to preparate Ganlong capsule-containing serum
Keke ZHANG ; Hao BAI ; Jinyu LÜ ; Yue JIN ; Rui LUO
Chinese Journal of Pathophysiology 2024;40(5):956-960
AIM:To investigate the optimal time of blood collection and the best concentration of Ganlong capsule(GLC)-containing serum for steatohepatitis.METHODS:Sixty C57BL/6J mice were gavaged with GLC at a dose of 90 mg/kg body weight,twice a day for 7 days.Control mice were administered the same volume of 0.9%saline.After 0.5,1,2 and 4 h from the last gavage,blood was collected to prepare GLC-containing serum.The LC-MS/MS was used to detect the inosine content of blank and drug-containing serum at different blood collection times to determine the optimal time.Subsequently,NCTC1469 cells stimulated with palmitic acid(PA)were treated with different concentrations of the GLC-containing serum.Nile Red staining was used to detect lipid droplet formation,and RT-qPCR was employed to as-sess the expression of intracellular fatty acid synthesis(Fabp1,Scd1)and fatty acid β-oxidation gene(Pparα).RE-SULTS:(1)LC-MS/MS detection revealed that the inosine concentration peaked 2 h after the last administration.(2)Nile red staining demonstrated that the GLC-containing serum exerted a dose-dependent decreasing trend of lipid droplets in hepatocytes induced by PA.(3)GLC-containing serum significantly downregulated the mRNA expression levels of lipo-genesis-genes(Fabp1 and Scd1)with a dose-dependent decreasing trend in the PA-induced NCTC1469 cells.The mRNA expression of genes associated with fatty acid β-oxidation(Pparα)were upregulated with a dose-dependent increasing trend.CONCLUSION:The 10%GLC-containing serum collected 2 hours after the last administration in mice has the best therapeutic effect for steatohepatitis.
10.Jisuikang formula promotes spinal cord injury repair in rats by activating the YAP/PKM2 signaling axis in astrocytes
Hao MAN ; Jianwei WANG ; Mao WU ; Yang SHAO ; Junfeng YANG ; Shaoshuo LI ; Jinye LÜ ; Yue ZHOU
Journal of Southern Medical University 2024;44(4):636-643
Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

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