1.Effect of echinacoside intervention on liver and pancreas injury in rats with acute pancreatitis and its mechanism
Minghe MA ; Zhuoma DAWA ; Chuanchuan LIU ; Haining FAN
Journal of Clinical Hepatology 2024;40(4):782-790
ObjectiveTo investigate the effect and mechanism of echinacoside (ECH) in improving liver injury in rats with acute pancreatitis by establishing a rat model of acute pancreatitis and liver injury. MethodsA total of 24 Sprague-Dawley rats were randomly divided into blank group (Con group), control group (Con+ECH group), acute pancreatitis group (AP group), and acute pancreatitis+ECH intervention (AP+ECH group). The rats were given intraperitoneal injection of 10 mg/kg ECH on day 7 before the establishment of the model of acute pancreatitis; at 24 hours after the last administration of cerulein, blood samples were collected via the abdominal aorta, and serum was separated for biochemical analysis including alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), albumin (Alb), total bilirubin (TBil), cholinesterase, blood amylase (Amy), and lipase (LPS). HE staining was used to observe the histopathological changes of the pancreas and the liver; transmission electron microscopy (TEM) was used to observe the microstructural changes of pancreas and liver tissue; ELISA was used to measure the levels of interleukin-1β (IL-1β), interleukin-16 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in liver tissue homogenate; immunohistochemistry was used to measure the levels of TNF-α and p-p65 NF-κB in pancreas and liver tissue; Western blot was used to measure the expression levels of NF-κB pathway proteins in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK test or the Dunnett’s T3 method was used for further comparison between two groups. ResultsCompared with the Con group, the AP group had significant increases in ALT, AST, GGT, LDH, ALP, TBil, Amy, and LPS (all P<0.01), as well as significant increases in the levels of IL-1β, IL-6, IL-10, and TNF-α in liver tissue homogenate (all P<0.01). ECH intervention reduced the levels of ALT, AST, GGT, LDH, ALP, TBil, AMY, and LPS and inhibited the secretion of IL-1β, IL-6, and TNF-α in rats with acute pancreatitis. HE staining showed that ECH intervention alleviated the vacuolar degeneration of acinar cells, inflammatory cell infiltration in pancreatic tissue, and the necrosis of hepatocytes compared with the AP group. TEM showed that compared with the AP group, there was a reduction in the degree of mitochondrial swelling in liver and pancreatic cells after ECH intervention. ECH intervention partially reversed the elevated expression levels of p-p65 NF-κB and TNF-α in liver and pancreatic tissue. In addition, the expression levels of MyD88, p-IκBα, p-IKKα, and p-p65 were upregulated in liver tissue of rats with acute pancreatitis, which could be partially reversed after ECH intervention. ConclusionEchinacoside can alleviate liver and pancreatic injury induced by acute pancreatitis by inhibiting the TLR4/MyD88/NF-κB pathway.
2.Study on the mechanism of a pyroptosis of renal podocytes in hypoxia and high glucose environment
Zhimin Meng ; Chuanchuan Liu ; Yaya Ji ; Qing Zhu ; Fengjiao Yin ; Ruixia Zhang ; Yinggui Ba
Acta Universitatis Medicinalis Anhui 2023;58(11):1916-1920
Objective :
To investigate the effects of hypoxia , high glucose single factor and hypoxia high glucose
compound factors on the pyroptosis of rat glomerular podocytes .
Methods :
Rat glomerular podocytes were cultured in vitro and randomly divided into control group , high glucose group , hypoxia group and hypoxia high glucose group , EdU method was used to detect the cell proliferation , transmission electron microscope was used to observe the morphology and size changes of nucleus and mitochondria , and Western blot was used to detect pyroptosis related proteins nucleotide⁃binding oligomerization domain⁃like receptor protein 3(NLRP3) , Cysteinyl aspartate specific proteinase⁃1(Caspase⁃1) , gasdermin( GSDMD) and inflammatory factor pro⁃interleukin⁃1β( Pro⁃IL⁃1β) , interleukin(IL) Ⅳ1β , IL⁃18 . The effect of hypoxia and high glucose on the pyroptosis of rat glomerular podocytes was analyzed .
Results :
EdU results showed that hypoxia and high glucose inhibited the proliferation ability of rat glomerlar podocytes (P < 0. 05) . The results of transmission electron microscopy suggested that hypoxia and high glucose promoted the occurrence of pyroptosis of rat glomerular podocytes . Western blot showed that hypoxia and high glucose promoted pyroptosis of rat glomerular podocytes , and increased the expression of pyroptosis related proteins NLRP3 , Caspase⁃1 and GSDMD , among which the expression of pyroptosis protein increased most significantly in hypoxia and high glucose group (P < 0. 05) . At the same time , it also increased the expression of pro⁃inflammatory factor Pro⁃IL⁃1β , IL⁃1β and IL⁃18 (P < 0. 05) .
Conclusion
hypoxia and high glucose can induce pyroptosis of rat glomerular podocytes , one of the mechanisms may be through affecting NLRP3 ⁃Caspase⁃1 ⁃GSDMD and its down⁃ stream inflammatory factors .
3.Hypoxia-preconditioned hUCMSC-Exos relieve hypoxic pulmonary hy-pertension by inhibiting pulmonary vascular EndMT
Yuxiang WANG ; Chuanchuan LIU ; Qingqing ZHANG ; Pan HUANG ; Hong LIU ; Yougang MA ; Xiaobo WANG ; Yating WANG ; Lan MA
Chinese Journal of Pathophysiology 2023;39(12):2193-2203
AIM:To investigate the effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-Exos)on pulmonary vascular endothelial-mesenchymal transition(EndMT)in hypoxic pulmonary hypertension(HPH).METHODS:(1)Primary hUCMSCs were isolated and cultured by tissue adhesion method,and hUCMSC-Exos were extracted by ultrafiltration and identified.(2)Twenty-four SPF male SD rats were ran-domly divided into normoxia(N)group,hypoxia(H)group,hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group,with 6 rats in each group.The rats in H group and intervention groups were placed in a cabin that simulated the hypoxic environment at an altitude of 5 000 m,and normoxic hUCMSC-Exos,hypoxia-precon-ditioned hUCMSC-Exos or equivalent volume of PBS were injected through the tail vein on the 3rd,5th,7th,10th and 14th days in hypoxia environment.After 21 d of modeling,the right ventricular systolic pressure(RVSP)and right ven-tricular hypertrophy index(RVHI)of the rats were detected,and the pathological changes of lung tissues were observed by HE staining.(3)After starvation for 12 h,human pulmonary arteriole endothelial cells(HPAECs)were randomly di-vided into normoxic control(N-Con)group,hypoxic model(H-Con)group,hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group.The migration ability and tube formation ability of HPAECs were detected by Transwell assay and tube formation experiment.The expression of CD31 and α-smooth muscle actin(α-SMA)in HPAECs was detected by immunofluorescence double-staining.The protein levels of CD31,VE-cadherin,α-SMA and vimentin in pulmonary vessels and HPAECs were assessed by Western blot.RESULTS:(1)The HPH rat model was suc-cessfully established after 21 d of hypoxia,and EndMT occurred in pulmonary vessels.Compared with N group,the levels of RVSP,RVHI,percentage of vascular wall area(WA%)and percentage of vascular wall thickness(WT%)in H group were significantly increased(P<0.01),pulmonary vascular wall thickening and the protein levels of CD31 and VE-cad-herin were significantly decreased(P<0.01),while the protein levels of α-SMA and vimentin were significantly increased in pulmonary vessels(P<0.05 or P<0.01).Compared with H group,the RVSP,RVHI,WA%and WT%(P<0.01)were significantly decreased(P<0.05 or P<0.01),and pulmonary vascular remodeling was attenuated after normoxic or hypoxia-preconditioned hUCMSC-Exos intervention.After hypoxia-preconditioned hUCMSC-Exos intervention,HPH pul-monary vascular remodeling and EndMT formation were significantly inhibited.(2)After 48 h of hypoxic treatment,the migration,tubule formation and EndMT of HPAECs were induced.Compared with H-Con group,cell migration and tube formation were significantly decreased after hypoxia-preconditioned hUCMSC-Exos intervention(P<0.01).The protein levels of CD31 and VE-cadherin were increased,while the protein levels of α-SMA and vimentin were decreased(P<0.05 or P<0.01).CONCLUSION:Hypoxia-preconditioned hUCMSC-Exos attenuate the formation of HPH pulmonary vascu-lar remodeling by inhibiting pulmonary vascular EndMT.
4.Effectiveness of Longji Daoyin exercise on adolescents of mild idiopathic scoliosis
LIU Lu, ZHANG Wei, HU Zengping, GAO Yang, GU Chuanchuan, YAN Yuntao, DU Shuangqing
Chinese Journal of School Health 2023;44(1):119-122
Objective:
To explore the effectiveness of spinal guidance exercise on adolescents of mild idiopathic scoliosis, so as to provide an experimental reference and method for promoting adolescents spinal health.
Methods:
From the scoliosis screening, 96 children who met the diagnostic criteria were selected in June 2021, and were divided into the experimental group and the control group, with 48 cases in each group. The experimental group received a 12 week Longji Daoyin exercise training, and the control group received health education, observation and monitoring. Before and after the experiment, the axial trunk rotation (ATR) and scoliosis Cobb angle of the two groups were tested respectively, and the subjective sensation of the patients was measured by Scoliosis Research Society-22(SRS-22) questionnaire.
Results:
After 12 weeks, the ATR and Cobb angles of the experimental group decreased [( 5.02± 2.85,7.59±3.94)°],compared to (7.08±2.84)° and (15.84±2.00)° before intervention( t =14.02, 17.09, P < 0.01 ). Scores of functional activity, self image and mental health in the SRS-22 score increased from (4.65±0.14)(3.49±0.21) and (3.99±0.17) to(4.77±0.14)(4.62±0.13)(4.42±0.13)( t =-4.86,-39.12,-13.92, P <0.01 ). The ATR and Cobb angles of the control group increased from (6.94±2.15)° and (15.82±1.76)° to (8.25±2.49)° and (18.63±3.12)°( t =7.44,8.99, P <0.01), and the scores of self image and mental health in the SRS-22 score decreased from (3.49±0.19) and (4.00±0.15) to (3.44±0.18) and (3.94±0.14)( t =-3.74,-4.39, P <0.05).
Conclusion
Early adolescent idiopathic scoliosis is easy to aggravate during the observation period. Longji Daoyin exercise is of preventive and therapeutic significance.
5.Immediate effect of small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation in improving the treatment of braces for adolescent idiopathic scoliosis
Lu LIU ; Wei ZHANG ; Yulei LIANG ; Yang GAO ; Guang ZUO ; Chuanchuan GU ; Tianci GAO
Journal of Acupuncture and Tuina Science 2023;21(1):34-39
Objective: To observe the immediate effect of small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation in improving the correction of braces for adolescent idiopathic scoliosis. Methods: A total of 50 cases of adolescent idiopathic scoliosis were selected and given brace correction first. The whole spine anteroposterior and lateral radiographs were taken, the Cobb angle was measured, and the visual analog scale (VAS) score of pain caused by brace wearing was recorded. After removal of the brace, small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation was performed once. After treatment, the same brace was put on again to take a whole spine anteroposterior radiograph, the Cobb angle was measured, and the VAS score was recorded. The changes in Cobb angle and VAS score after manipulation were compared, and the immediate efficacy was evaluated. Results: After the manipulation, the Cobb angle was significantly smaller than that before treatment (P<0.01) and the VAS score was significantly lower than that before treatment (P<0.01). Conclusion: Small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation can improve the immediate efficacy of brace in treating adolescent idiopathic scoliosis and relieve the pain caused by brace wearing at the same time.
6.Ultrasonographic features of adenoma of the nonpigmented ciliary epithelium
Dongjun LI ; Wenli YANG ; Wenbin WEI ; Xiaolin XU ; Ziyang WANG ; Wei CHEN ; Qi ZHAO ; Yifeng LI ; Rui CUI ; Lin SHEN ; Qian LIU ; Chuanchuan WEI
Chinese Journal of Ocular Fundus Diseases 2022;38(3):191-196
Objective:To analyze the ultrasonographic features of adenoma of the nonpigmented ciliary epithelium (ANPCE).Methods:A retrospective series of case studies. From January 2014 to October 2021, 31 patients (31 eyes) with ANPCE (ANPCE group) were diagnosed in the eye center of Beijing Tongren Eye Center of Beijing Tongren Hospital, Capital Medical University, and 17 patients (17 eyes) with ciliary body melanoma (control group) diagnosed at the same time were selected as the control group. There was no significant difference in age ( t=-0.564) and sex composition ratio ( χ 2=0.182) between the two groups ( P=0.576, 0.670). All patients underwent ultrasound biomicroscopy to obtain the measurement parameters: tumor height, maximum basal diameter, maximum diameter, ratio of maximum diameter to basal diameter and ratio of maximum diameter to height; tumor location, shape, internal echogenicity intensity, echogenicity uniformity, degree of sound attenuation, invasion of iris, anterior displacement of the iris, lens subluxation were observed. The measurement parameters and observation indexes of the two groups were compared by independent sample t-test and χ 2 test. Receiver operating characteristic (ROC) curve was drawn, area under the ROC curve (AUC) was determined, and parameter indicators with differential diagnosis value were screened. Results:The maximum diameter, height, maximum basal diameter, ratio of the maximum diameter to the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumors in the ANPCE group and the control group were 5.64±0.98 mm, 4.24±0.59 mm, 3.66±0.71 mm, 1.58±0.34, 1.34±0.19 and 7.82±2.03 mm, 4.47±2.44 mm, 7.02±1.96 mm, 1.13±0.16, 2.09±1.06. The maximum diameter, the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumor in the ANPCE group were all smaller than those of the control group, and the ratio of the maximum diameter to the maximum basal diameter was greater than that of the control group, and the differences were statistically significant ( t=-4.159,-6.808, -2.924, 6.257; P<0.05). The tumors in the ANPCE group were mainly spherical (87.1%, 27/31), with no significant acoustic attenuation (77.4%, 24/31), less invading the root iris (77.4%, 24/31), and the tumors were mostly located in the ciliary body coronal (74.2%, 23/31); tumors in the control group were mainly hemispherical (47.1%, 8/17) or spherical (47.1%, 8/17), with significant sound attenuation (76.5%, 13/17), most of the tumors invaded the iris (70.6%, 12/17), and the tumors were mostly located from the pars plana to the coronal (76.5%, 13/17). There were statistically significant differences in the position, shape, sound attenuation degree, and whether it invaded the iris between the two groups of eyes ( χ 2=15.132, 19.767, 13.118, 10.581; P<0.05). The results of ROC curve analysis showed that the ratio of the largest diameter to the largest base diameter, the degree of sound attenuation and the AUC of whether the iris was violated were higher, which were 0.881, 0.769, and 0.740, respectively. Conclusions:Ultrasound biomicroscopy is helpful in the diagnosis and differential diagnosis of ANPCE and ciliary body melanoma. The ratio of maximum diameter to maximum basal diameter, the degree of sound attenuation and whether it invades the root iris are important parameters to distinguish the two tumors.
7.Study on Spectrum-effect Relationship of Anti-inflammatory and Analgesic Effects of Ethyl Acetate Extract from Zhuang Medicine Stahlianthus involucratus
Jie LIANG ; Huihua CHEN ; Chuanchuan YANG ; Yupin CAO ; Jun CHEN ; Yaohua LI ; Xiaosi CHEN ; Xianfu LIU
China Pharmacy 2021;32(14):1721-1727
OBJECTIVE:To i nvestigate the spectrum-effect relationship of analgesic and anti-inflammatory effects of ethyl acetate extract from Zhuang medicine Stahlianthus involucratus from different habitats. METHODS :Ten batches of S. involucratus from different habitats were used as samples to investigate the anti-inflammatory and analgesic activities of ethyl acetate extracts by xylene induced ear swelling test and acetic acid induced writhing test in mice. HPLC fingerprints of 10 batches of ethyl acetate extract from S. involucratus were established and their similarity was evaluated by using Similarity Evaluation System of TCM Chromatogram Fingerprint (2012 edition),and the common peaks were identified by comparison with the control. The spectrum-effect relationship of anti-inflammatory and analgesic effects of ethyl acetate extract from S. involucratus were analyzed on the basis of Pearson correlation coefficient (auricle swelling degree and writhing times in 15 min as pharmacodynamic indexes )and Grey relational analysis (inhibition rate of ear swelling and analgesic rate as pharmacodynamic indexes ). RESULTS : batches of ethyl acetate extract from S. involucratus had obvious anti-inflammatory and analgesic effects ; inhibition rates of ear swelling in mice were 46.43%-55.16%,and the analgesic rates of mice were 45.56%-52.72%. A total of 18 common peaks were identified in 10 batches of samples ,andthe similarity between them and the control fingerprint was 0.994-0.997. Compared with substance control ,the pea ks 1,2 and 4 were identified as protocatechuic acid , p-hydroxy- 0771-4953513。E-mail:liangjie1101@126.com benzoic acid and p-hydroxybenzaldehyde,respectively. Results of Pearson correlation analysis showed that peak 10 and peak 18 were significantly negative correlated with auricle swelling degree and writhing times in 15 min(r were values -0.853,-0.738,P values were 0.002,0.015,respectively). Results of Gray correlation degree analysis showed that the correlation degree of 18 common peaks with inhibition rate of ear swelling and analgesic rate were all greater than 0.65;among them ,peaks 14,1(protocatechuic acid ),17,9,4(p-hydroxybenzaldehyde),2(p-hydroxybenzoic acid ), 16,7 and 6 showed the relatively high correlation degree (correlation degree >0.7);peak 1(protocatechuic acid ),17,14,9,16,2 (p-hydroxybenzoic acid )and 4(p-hydroxybenzaldehyde)showed the relatively high correlation degree (correlation degree >0.7). CONCLUSIONS:The ethyl acetate extract of S. involucratus show good anti-inflammatory and analgesic effects. Peak 1 (protocatechuic acid ),2(p-hydroxybenzoic acid ),10,14,17,18 may be its main active ingredients.
8.A Case of Human Hepatic Alveolar Echinococcosis Accompanied by Lung and Brain Metastases
Chuanchuan LIU ; Haining FAN ; Ri-li GE
The Korean Journal of Parasitology 2021;59(3):291-296
Alveolar echinococcosis (AE) is considered as a fatal zoonosis caused by the larvae of Echinococcus multilocularis. The lungs and brain are the most common metastatic organs. We report a human case of hepatic alveolar echinococcosis accompanied by lung and brain metastasis. In particular, the patient had a history of tuberculosis and the lung lesions were easily misdiagnosed as lung abscesses. The lesions of liver and lung underwent radical resection and confirmed as alveolar echinococcosis by pathological examination. The patient had no surgical complications after operation and was discharged after symptomatic treatment. Unfortunately, the patient later developed multiple intracerebral AE metastases. We required the patient to take albendazole orally for life and follow up.
9.A Case of Human Hepatic Alveolar Echinococcosis Accompanied by Lung and Brain Metastases
Chuanchuan LIU ; Haining FAN ; Ri-li GE
The Korean Journal of Parasitology 2021;59(3):291-296
Alveolar echinococcosis (AE) is considered as a fatal zoonosis caused by the larvae of Echinococcus multilocularis. The lungs and brain are the most common metastatic organs. We report a human case of hepatic alveolar echinococcosis accompanied by lung and brain metastasis. In particular, the patient had a history of tuberculosis and the lung lesions were easily misdiagnosed as lung abscesses. The lesions of liver and lung underwent radical resection and confirmed as alveolar echinococcosis by pathological examination. The patient had no surgical complications after operation and was discharged after symptomatic treatment. Unfortunately, the patient later developed multiple intracerebral AE metastases. We required the patient to take albendazole orally for life and follow up.
10.A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving
Xiaojuan ZHANG ; Chuanchuan HE ; Yun SUN ; Xiaoguang LIU ; Yan CHEN ; Chen CHEN ; Ruicong YAN ; Ting FAN ; Tan YANG ; Yao LU ; Jun LUO ; Xiang MA ; Guangya XIANG
Acta Pharmaceutica Sinica B 2021;11(11):3608-3621
Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.


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