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1.
Pak J Pharm Sci ; 36(4): 1217-1225, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37599498

ABSTRACT

High-fat diet (HFD) feeding is a risk factor for kidney damage with limited treatment options. This study explored the effect of total glucosides of paeony (TGP) for treating obesity-related kidney damage. C57BL/6 mice fed with HFD were used for in vivo experiments. Body weight, lipid and renal function indicators were measured. Hematoxylin and eosin, Masson, Sirius Red and F4/80 immunohistochemical staining were performed. Fibrosis levels, inflammatory factors, MyD88, IκB and p-Jun NH2-terminal kinase (JNK) were detected. SV40 cells were incubated with palmitic acid, transfected with siRNA MyD88 and/or treated with TGP. The expression of MyD88, IκB, p-JNK, fibrosis and inflammatory factors were detected. TGP considerably decreased HFD-induced body weight gain and serum lipid concentration but improved renal function. In addition, TGP inhibited renal fibrosis and inflammation and reduced MyD88 and p-JNK levels, whereas increased IκB levels. Moreover, silencing MyD88 decreased p-JNK levels while increasing IκB levels which may be the mechanism of TGP treatment. Our findings demonstrated that TGP treatment can ameliorate HFD-induced kidney injury via regulating JNK and IκB signals mediated by MyD88.


Subject(s)
Diet, High-Fat , Paeonia , Mice , Animals , Mice, Inbred C57BL , Diet, High-Fat/adverse effects , Myeloid Differentiation Factor 88 , Inflammation/drug therapy , Inflammation/prevention & control , Body Weight , Glucosides , Kidney/physiology , Lipids
2.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991279

ABSTRACT

This paper first summarizes the cognition and understanding of online teaching, then introduces the active design and practice of online teaching in Harbin Medical University, and fully comprehends the quality of online teaching through the feedback to teachers and students. Through the investigation, the research group found that there are problems in online teaching, including teachers' difficulty in applying the teaching platform efficiently, limited Internet speed and hardware equipment, insufficient understanding and attention of individual teachers to online teaching, insufficient interaction between teachers and students, and difficulty in carrying out experiments and practical teaching. In this regard, the research group proposed countermeasures to change online teaching concept, reform online teaching methods, improve the function of online teaching platform, and optimize online course resources in order to timely summarize the online teaching situation, improve the shortcomings and promote advanced experience, and ensure the quality of follow-up online teaching.

3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014680

ABSTRACT

AIM: By analyzing the effect of gambogenic acid (GNA) on the mRNA expression profile of melanoma xenograft model mice, the possible mechanism of GNA in the treatment of melanoma was explored. METHODS: The inhibitory effect of GNA on melanoma cells was studied by measuring the cell survival rate by MTT method in vitro and observing the cell morphology under an inverted microscope. In the in vivo experiment, the effect of GNA on the growth of xenografted tumors in melanoma mice was observed by comparing the results of HE (hematoxylin-eosin) staining and immunohistochemistry (Ki-67), and the tumor weight and tumor weight ratio were recorded. RNA-seq sequencing technology was used to sequence the GNA medium-dose group and the model group, and the screened mRNAs were analyzed by GO and KEGG, and finally the screening results of differentially expressed genes were verified by real-time quantitative fluorescent PCR. RESULTS: After different doses of GNA acted on the melanoma mouse model, a large area of necrosis occurred in the tumor tissue of the model mouse, and the tumor growth was significantly inhibited. A total of 36 differentially expressed mRNAs were identified by mRNA sequencing, of which 30 were up-regulated and 6 were down-regulated. The possible functions of the mRNAs were predicted according to the genomic adjacency analyzed by GO and KEGG. The expression of the selected differential mRNAs was further verified by real-time quantitative PCR technology. The results showed that the mRNA expressions of Cidec, Ces1d, Mylk4, and Igkv9-123 were up-regulated, and the mRNA expressions of Ryr3 and Hapln1 were down-regulated. CONCLUSION: GNA can inhibit the proliferation of melanoma cells in vitro and in vivo, and its mechanism is related to the regulation of cytokine-cytokine receptor interaction, NF-κB, MAPK, and other pathways of mRNA expression.

4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014905

ABSTRACT

AIM: To investigate the effects and protective mechanism of Tianma Gouteng (TGY) against rotenone (Rot) damage in PC12 cells. METHODS: PC12 cells were treated with Rot to establish nerve injury model and cell survival rate was determined by MTT colorimetry to determine the optimal modeling concentration of Rot and effective intervention concentration of TGY. Lipid reactive oxygen species (ROS) were detected by flow cytometry and fluorescence intensity was observed by inverted fluorescence microscope. The biochemical methods were used to detect, superoxide dismutase (SOD), glutathione (GSH) levels and activity and the contents of malondialdehyde (MDA). Transmission electron microscopy observed morphological change of mitochondria and protein expression of glutathione peroxidase 4 (GPX4), long chain lipoyl-coa synthase 4 (ACSL4) and lysophospholipid cholinyltransferase 3 (LPCAT3) were detected by western blot. RESULTS: The survival rate of cells treated with 0.6 μmol/L Rot for 24 h was close to 50%(56.7%±9.9%). Pretreatment with TGY for 12 h could inhibit the damage of Rot. At the same time, the leakage rate of lactate dehydrogenase (LDH) was reduced in a dose-dependent manner. Lipid ROS content increased after the treatment of Rot, whereas pretreatment with TGY effectively reduced lipid ROS content, decreased MDA level and increased SOD activity and GSH level in damaged cells in cells damaged by Rot. Transmission electron microscopy showed that the mitochondria of PC12 cells were shrunk after the damage of 0.6 μmol/L Rot and the mitochondrial morphology of PC12 cells was improved to some extent after preprotection of TGY compared with normal group. Western blot results showed that TGY pretreatment could increase the expression of GPX4 and reduce the expression of ACSL4 and LPCAT3 after damage of Rot to a certain extent. CONCLUSION: TGY can improve nerve damage by up-regulating the expression of GPX4 protein, down-regulating the expression of ACSL4 and LPCAT3 protein to inhibit the oxidation of unsaturated fatty acids, reduce the level of lipid peroxidation and ROS content.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1015033

ABSTRACT

AIM: To investigate the protective mechanism of gastrodin against hydrogen peroxide (H

6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-911419

ABSTRACT

The measurement of serum alkaline phosphatase (ALP) levels has been widely used in the clinical setting. However, isolated elevation of serum ALP levels is also commonly seen and needs to be extensiuely evaluated Herein, we present a case of gastric adenocarcinoma with disseminated carcinomatosis of the bone marrow (DCBM). In this case, isolated elevation of serum ALP levels was the only clinical manifestation with no other notable symptom. Additionally, imaging studies including whole body computed tomography (CT) and positron emission tomography-CT (PET-CT) were all negative, which resulted in the misdiagnosis of Paget′s disease of bone initially. This highlights that malignancies involving bones presenting with isolated elevation of serum ALP levels might be misdiagnosed in asymptomatic individuals.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-865992

ABSTRACT

Medical curriculum integration is of great significance for reforming traditional medical education models and cultivating new medical talents with competency. On the basis of reviewing the concepts and development history of medical curriculum integration in China, this article sorts out three relatively mature medical curriculum integration models based on the practice of medical education reform in China, namely, organ-system-based curriculum model, and problem-based curriculum model and modular curriculum integration model. It also points out the difficulties of the current curriculum integration reform in medical colleges and universities from the aspects of the construction of teaching staff, the construction of integrated curriculum teaching materials, the design and connection of curriculum, and the assessment and evaluation. Finally, we should deeply analyze the concept of curriculum integration and create a curriculum model suitable for the reality of China's medical education in practice, hoping to provide reference for the practice of medical curriculum integration reform in China.

8.
China Pharmacy ; (12): 889-895, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-817009

ABSTRACT

OBJECTIVE: To study the improvement effect and related mechanism of pyragrel sodium on nerve function of cerebral ischemia-reperfusion injury model rats. METHODS: Totally 72 SD rats were randomly divided into sham operation group, model group, positive control group (dizocilpine 0.8 mg/kg), pyragrel sodium low-dose, medium-dose and high-dose groups (20, 30, 45 mg/kg), with 12 rats in each group. Except sham operation group received sham operation, rats in the other groups were treated with middle cerebral artery ligation to induce cerebral ischemia-reperfusion injury model. The rats in the sham operation group and the model group were injected with the constant volume of normal saline, for consecutive 6 d, and the interval of administration was 24 hours. After 24 h reperfusion and last medication, neurological deficit score and postural reflex score in rats were evaluated. The situation of cerebral injury (including whole brain, insular cortex, putamen, striatum, somatic cortex, amygdala, motor cortex) was evaluated by using micropositron emission tomography. The rats were sacrificed, and the situation of cerebral infarction was observed by TTC and cerebral infarction volume was calculated. Na+-K+-ATPase, Ca2+-ATPase activity and Glu content were detected by ELISA. RESULTS: Compared with sham operation group, neurological deficit score and postural reflex score increased significantly in model group 24 h after ischemia-reperfusion and after last medication (P<0.05 or P<0.01). After 24 hours of cerebral ischemia-reperfusion and the last medication, SUV of brain tissue, SUV ratio of right left brain of different cerebral areas were decreased significantly (P<0.01). After last medication, the percentage of cerebral infarction volume was increased significantly (P<0.01); the activities of Na+-K+-ATPase and Ca2+-ATPase were decreased significantly (P<0.01), while Glu content was increased significantly (P<0.01). Compared with model group, above indexes of pyragrel sodium low-dose, medium-dose and high-dose group, positive control group were all improved significantly (P<0.05 or P<0.01). CONCLUSIONS: Pyragrel sodium can improve cerebral ischemia-reperfusion injury and nerve function, which is related to the activity up-regulation of Na+-K+-ATPase and Ca2+-ATPase, the down-regulation of Glu content.

9.
Biomed Res Int ; 2018: 9153496, 2018.
Article in English | MEDLINE | ID: mdl-29750173

ABSTRACT

INTRODUCTION: All adult medulloblastoma (AMB) patients should be treated with craniospinal irradiation (CSI) postoperatively. Because of the long irradiation range, multiple radiation fields must be designed for conventional radiotherapy technology. CSI can be completed in only one session with helical tomotherapy (HT). We evaluated the dose of HT, volumetric intensity modulated arc therapy (VMAT), and three-dimensional conformal radiotherapy (3D-CRT) of AMB and the results of 5 cases of AMB treated with HT. METHODS: Complete craniospinal and posterior cranial fossa irradiation with HT, VMAT, and 3D-CRT and dose evaluation were performed. And results of 5 cases of AMB treated with HT were evaluated. RESULTS: A large volume of tissue was exposed to low dose radiation in the organs at risk (OAR), while a small volume was exposed to high dose radiation with HT. The conformity and uniformity of the targets were good with HT and VMAT, and the volume of targets exposed to high dose with VMAT was larger than that of HT. The uniformity of 3D-CRT was also good, but the dose conformity was poor. The main toxicity was hematologic toxicity, without 4th-degree bone marrow suppression. There was 3rd-degree inhibition in the white blood cells, hemoglobin, and platelets. The three female patients suffered menstrual disorders during the course of radiation. Two female patients with heavy menstruation suffered 3rd-degree anemia inhibition, and 2 patients suffered amenorrhea after radiotherapy. Although menstrual cycle was normal, the third patient was not pregnant. CONCLUSION: CSI with HT is convenient for clinical practice, and the side effects are mild. With good conformity and uniformity, VMAT can also be used for selection in CSI. For poor conformity, 3D-CRT should not be the priority selection for CSI. In female patients, the ovaries should be protected.


Subject(s)
Cerebellar Neoplasms/radiotherapy , Medulloblastoma/radiotherapy , Radiotherapy, Conformal/methods , Radiotherapy, Intensity-Modulated/methods , Adolescent , Adult , Female , Humans , Male , Organs at Risk/radiation effects , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Retrospective Studies , Young Adult
10.
Sci Rep ; 8(1): 5595, 2018 04 04.
Article in English | MEDLINE | ID: mdl-29618828

ABSTRACT

This study is to analyze the radiation dose of head, body and tail of hippocampus (HC) of nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). Evaluate cognitive function of patients with Wechsler adult intelligence scale-Chinese revised (WAIS-CR). HC were segmented into HC head (HH), HC body (HB) and HC tail (HT) and the indexes were then analyzed. WAIS-CR was tested before and 3months after radiotherapy. The mean radiation dose of left and right HC was (1147 ± 976)cGy, (1011 ± 602)cGy respectively. The radiation dose and the volume exposed in different dose of HH, HB and HT decreased in turn. For 5 patients, before and after radiotherapy, the regular-order score was 8.60 ± 1.34, 8.0 ± 1.00 (P = 0.43), while the reverse-order score was 5.80 ± 0.84, 5.20 ± 0.84 (P = 0.07). The radiation dose of HH, HB and HT was different, and the radiation dose of HH was the highest, which should be emphasized especially.


Subject(s)
Hippocampus/radiation effects , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/radiotherapy , Adult , Antineoplastic Agents/therapeutic use , Female , Gamma Rays , Hippocampus/diagnostic imaging , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Radiation Dosage , Radiotherapy, Intensity-Modulated , Survival Rate , Young Adult
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-700172

ABSTRACT

Objective To study the detection of Na+/H+exchanger regulatory factor 3(NHERF3) protein expression in renal carcinoma and its correlation with malignant biological behavior. Methods Renal clear cell carcinoma and their adjacent tissues of forty- eight patients were collected. Immunohistochemical method was used to detect the positive expression of NHERF3 protein,and specific expression was detected by Western-blot.Patients were further divided into high NHERF3 group and low NHERF3 group according to median expression of NHERF3 protein,and each group had 24 cases.The expressions of proliferation,invasion and autophagy genes in tumor tissues were detected by fluorescent quantitative PCR.Results The positive rate of NHERF3 protein and the expression of NHERF3 protein in renal carcinoma tissue was significantly lower than that in paracancerous tissue(P<0.05).Expressions of proliferation genes such as k-Ras,c-Myc,TRPC1 mRNA in low NHERF3 group were higher than those in high NHERF3 group:141.74 ± 18.95 vs. 100.00 ± 0.00, 135.88 ± 16.32 vs. 100.00 ± 0.00, 137.21 ± 16.98 vs.100.00 ± 0.00;MIIP,FOXO1 mRNA levels were lower than those in high NHERF3 group: 43.19 ± 5.88 vs. 100.00 ± 0.00, 38.76 ± 4.51 vs. 100.00 ± 0.00; expressions of invasion genes such as CD74, Fascin, MACC1, TRPM8 mRNA were significantly higher than those in high NHERF3 group:152.18 ± 17.64 vs. 100.00 ± 0.00, 146.29 ± 17.63 vs. 100.00 ± 0.00, 139.76 ± 15.82 vs. 100.00 ± 0.00,150.47 ± 17.95 vs.100.00 ± 0.00;expressions of autophagy genes such as Beclin-1,LC3 mRNA were significantly lower than those in high NHERF3 group: 63.21 ± 7.09 vs. 100.00 ± 0.00, 56.28 ± 7.15 vs. 100.00 ± 0.00; EZH2 mRNA level was higher than that in high NHERF3 group:159.47 ± 17.82 vs.100.00 ± 0.00,and there were significant differences(P<0.05).Conclusions The positive rate of NHERF3 protein expression and the amount of protein expression in renal carcinoma tissue is increased, and the specific expression is closely related to tumor proliferation, invasion and activity of autophagy.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-813171

ABSTRACT

To investigate the relationship between single nucleotide polymorphisms (SNPs) of CACNA1C (SNPs rs58619945, rs7316246 and rs216008) and susceptibility of chronic spontaneous urticaria (CSU) as well as the curative effect of non-sedating antihistamine drugs.
 Methods: Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI) changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs (rs58619945, rs7316246 and rs216008) of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs (desloratadine, mizolastine, fisofenadine) in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.
 Results: Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR(95%CI)=0.660(0.470-0.925), P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls. Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs (rs58619945: OR=0.843, P=0.454; rs7316246: OR=2.103, P=0.102; rs216008: OR=0.237, P=0.363). There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR(95%CI)=0.480(0.247-0.933), P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine.
 Conclusion: The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.


Subject(s)
Humans , Calcium Channels, L-Type , Genetics , Chronic Disease , Genetic Predisposition to Disease , Histamine H1 Antagonists, Non-Sedating , Therapeutic Uses , Loratadine , Therapeutic Uses , Polymorphism, Single Nucleotide , Prognosis , Retrospective Studies , Urticaria , Drug Therapy , Genetics
13.
Oncotarget ; 8(33): 54304-54319, 2017 Aug 15.
Article in English | MEDLINE | ID: mdl-28903343

ABSTRACT

This study is to explore the effect of total flavonoids from Radix Tetrastigmae (TF) against hepatic cancer and discuss the acting mechanism. Proliferation of HepG2 cells was promoted by PGE2 and Butaprost. Using AH6809 as the positive control, the inhibitory effect of TF on additional cell line was detected through a CCK-8 assay, the apoptosis rate was detected by flow cytometry, and the nuclear morphology of cells were observed by Hochest33258 staining. Then PCR was applied to determine the mRNA expression. The corresponding Protein expression were determined by Western Blot. The effects of TF on the body weight, tumor growth volume and tumor inhibition rate were observed in nude mice model of human hepatocellular carcinoma by vivo experiments. The results showed TF had an obvious inhibitory effect on HepG2 cells with a significant dose-dependent manner (P<0.01). Pyknosis was found under the fluorescence microscope after TF treatment for 24h by Hochest33258 staining. Typical features of apoptosis were observed in HepG2 cells treated with TF and the apoptosis rate increased with increase of concentration of the TF. mRNA expression levels of GSK-3ß, Akt, VEGF, COX-2 and ß-catenin were down regulated greatly by the TF in HepG2 cells. Moderate and high concentrations of TF led to an obvious down regulation of GSK-3ß, p-GSK-3ß, Akt, p-Akt, VEGF, COX-2 and ß-catenin in HepG2 cells, while p-ß-catenin was up regulated. The tumor inhibition rates with high, medium and low dose of TF were 64.07%, 53.64%, 46.69%, respectively. The inhibitory effect of total flavonoids on tumor growth in mice was better than that of CTX, and the inhibitory effect of TF on tumor growth was less than CTX. TF exhibited a significant inhibitory effect on HepG2 cells, promoting the apoptosis of HepG2 cells in a dose-dependent manner. TF was also regulatory of the COX-2-Wnt/ß-catenin signaling pathway, which was presumed to be the working mechanism of Tetrastigmae.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-808879

ABSTRACT

Objective@#To investigate the effect of icariin (ICA) on the bisphenol A (BPA)-enhanced proliferation function of thyroid carcinoma cell B-CPAP and underlying mechanism.@*Methods@#The proliferation of Gastric B-CPAP cell line was evaluated by cell counting kit-8 (CCK-8). Apoptosis and ROS expression in B-CPAP cells were detected by flow cytometry. The expression of superoxide dismutase (SOD) and malondialdehyde (MDA) in B-CPAP cells were measured by individual assay kits. The expressions of Bcl-2 and γ-HA2X were detected by Western blot. SPSS 18.0 software was used to analyze the data.@*Results@#B-CPAP cell activity was promoted by treatment with 3×10-7mol/L BPA for 48 h, with significant difference in absorbance between BPA and control groups (1.089±0.053 vs 0.935±0.010, P<0.05). The cell activities of BPA+ ICA25, BPA+ ICA50, BPA+ ICA100 and BPA+ ICA200 groups was 0.780±0.036, 1.007±0.050, 0.958±0.033 and 0.625±0.064, respectively (all P<0.01). The proliferation of B-CPAP cells treated with BPA for 72 hours showed a similar trend to 48 hours. There was no significant difference between all treatment groups in 24 hours. The apoptosis rate was (19.272±0.186)% in BPA-treated cells, and was (22.412±0.238)% in control cells (P<0.05). The apoptosis rates of BPA+ ICA50 and BPA+ ICA200 groups were (23.688±0.412)% and (30.270±0.696)%, respectively (P<0.01). The intracellular accumulation of ROS in BPA, BPA+ ICA50, and BPA+ ICA200 groups were 806±21, 1 772±37, 2 041±16, respectively (P<0.01). The expressions of anti-apoptotic protein Bcl-2 in control, BPA, BPA+ ICA50, BPA+ ICA200 groups were 7 120±151, 9 801±286, 5 902±171 and 4 203±216, respectively (P<0.01).@*Conclusion@#BPA can promote the proliferation of thyroid carcinoma B-CPAP cells and decrease the apoptosis of cells, and this effect can be inhibited by ICA. The possible mechanism is to induce high expression of intracellular ROS and inhibit the expression of antioxidase system, leading to cell oxidative damage, thereby inducing apoptosis.

15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-487372

ABSTRACT

Objective To compare and evaluate the methods of building model of cervical spondylosis of vertebral artery type (CSA)rats by measuring the learning and memory ability,anxiety and depression,and degree of nervous tension of three kinds of CSA model rats.Methods We randomly divided 120 rats into mixed modeling group,bone graft compression modeling group,mechanical balance disorder modeling group,and blank control group with 30 rats in each.Morris water maze,elevated plus maze test and open field test were used to detect and compare the rats’abilities of learning and memory,anxiety and depression,and degree of nervous tension.We then evaluated the three CSA rat models.Results Compared with those in the blank group,the learning and memory abilities in the mixed modeling, bone graft compression and mechanical balance disorder modeling rats were significantly decreased,the anxiety and depression and degree of nervous tension were significantly increased (P<0.05).Compared with bone graft compression and mechanical balance disorder modeling groups,the mixed modeling group could restore the characteristics of CSA.Conclusion The three kinds of modeling methods can successfully reproduce the CSA animal model;the mixed modeling is superior and thus worthy of promotion.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-465565

ABSTRACT

After the necessity to compile n the union catalog of minority nationality medical documents in Yunnan Province was analyzed according to the scattered collection of minority nationality medical information resources and no available standard minority nationality medical documents catalog, how to compile it was discussed from the aspects of the collection and catalog organization of literature information resources, and quality control of bibliographic data, in order to construct the support system for minority nationality medical information resources.

17.
PLoS One ; 9(1): e83604, 2014.
Article in English | MEDLINE | ID: mdl-24427275

ABSTRACT

Lung cancer is one of the most common types of cancer and causes 1.38 million deaths annually, as of 2008 worldwide. Identifying natural anti-lung cancer agents has become very important. Gambogenic acid (GNA) is one of the active compounds of Gamboge, a traditional medicine that was used as a drastic purgative, emetic, or vermifuge for treating tapeworm. Recently, increasing evidence has indicated that GNA exerts promising anti-tumor effects; however, the underlying mechanism remains unclear. In the present paper, we found that GNA could induce the formation of vacuoles, which was linked with autophagy in A549 and HeLa cells. Further studies revealed that GNA triggers the initiation of autophagy based on the results of MDC staining, AO staining, accumulation of LC3 II, activation of Beclin 1 and phosphorylation of P70S6K. However, degradation of p62 was disrupted and free GFP could not be released in GNA treated cells, which indicated a block in the autophagy flux. Further studies demonstrated that GNA blocks the fusion between autophagosomes and lysosomes by inhibiting acidification in lysosomes. This dysfunctional autophagy plays a pro-death role in GNA-treated cells by activating p53, Bax and cleaved caspase-3 while decreasing Bcl-2. Beclin 1 knockdown greatly decreased GNA-induced cell death and the effects on p53, Bax, cleaved caspase-3 and Bcl-2. Similar results were obtained using a xenograft model. Our findings show, for the first time, that GNA can cause aberrant autophagy to induce cell death and may suggest the potential application of GNA as a tool or viable drug in anticancer therapies.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Autophagy/drug effects , Lung Neoplasms/metabolism , Terpenes/pharmacology , Xanthones/pharmacology , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Autophagy/genetics , Beclin-1 , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Gene Knockdown Techniques , HeLa Cells , Humans , Lung Neoplasms/genetics , Lysosomes/metabolism , Male , Membrane Proteins/genetics , Mice , Phagosomes/metabolism , Xanthenes , Xenograft Model Antitumor Assays
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-454432

ABSTRACT

After a description of the development in Chinese minority medicine and medical documents, the class (R29) for Chinese minority medical documents offered in Chinese Library Book Classification,5th edition was analyzed. The limitations for the classification of Chinese minority medical documents offered in Chinese Library Book Classifi-cation,5th editionwere pointed out, including no classes for the modern researches and subjects in Chinese minority medical documents , with strategies put forward for adding classes in R29 for Chinese minority medical documents in Chinese Library Book Classification,5th edition.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-354214

ABSTRACT

To explore gambogenic acid (GNA)-induced apoptosis and underlying mechanism in vivo. A549 nude mice xenografts were used as in vivo model to study anticancer effect of GNA by observing tumor growth curve and weight of the tumor. Ultrastructure of A549 cells treated by GNA was observed by TE. Expression of COX-2 and VEGF were detected by immunohistochemistry. TUNEL assay was applied in examining apoptosis index of tumor cells. The tumor isolated from mice treated by GNA (8, 16 mg kg(-1)) took on a slow growth condition compared with control group. The results suggested that weight and volume of the tumor from experimental groups were remarkably decreased compared with control group (P < 0.05). Ultrastructure change of the tumor, such as vacuolization, abnormal distribution of the heterochromosome, volume of the tumor cells, even apoptotic bodies, were observed in GNA-treated group. While no apparent morphological change was observed in the normal group. Typical apoptotic characteristics could be distinctly observed in the mouse treated by GNA for 20 days and apoptosis index in GNA-treated group was significantly higher than model group. Expression of COX-2 and VEGF were significantly down-regulated in GNA-treated groups in comparison with control group (P < 0.01). These results indicate that GNA could affect the development and progression of A549 cells through inducing apoptosis, mediating the expression of VEGF in vascular cells and COX-2 in tumor cells.


Subject(s)
Animals , Humans , Male , Mice , Antineoplastic Agents, Phytogenic , Therapeutic Uses , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cyclooxygenase 2 , Metabolism , Immunohistochemistry , In Situ Nick-End Labeling , Lung Neoplasms , Drug Therapy , Metabolism , Mice, Inbred BALB C , Mice, Nude , Microscopy, Electron, Transmission , Terpenes , Therapeutic Uses , Vascular Endothelial Growth Factor A , Metabolism , Xanthenes , Xanthones , Therapeutic Uses , Xenograft Model Antitumor Assays
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-354213

ABSTRACT

It is well known that puerarin possesses protective activity on neurodegenerative diseases. However, the exact path way involved in the protective effect of puerarin on MPP+ -induced cell death is unclear. In this study, we focused on mitochondria im pairment in the apoptotic process of MPP+ -elicited SH-SY5Y cells and detected the protection of puerarin. As evidenced by Trypan blue assay, the cell viability was significantly decreased by 1 mmol x L(-1) MPP+, but reversed by different concentrations puerarin pre treatment. Flow cytometer analysis revealed that MPP+ -induced SH-SY5Y cells apoptosis and arrested the cells in G2/M phase, where as puerarin pretreatment concentration dependently reversed the apoptosis ratio. In addition to the apoptosis ratio, 50.0 micromol x L(-1) puerarin pretreatment even altered the MPP+ -induced G2/M phase arrest. JC-1 assay suggested that MPP+ significantly opened MMP of the SH-SYSY cells; pretreatment with puerarin attenuated the deterioration of the MMP. Both ELISA and Western blotting showed that puerarin prevented the release of cytochrome c from the mitochondrial interior to the cystol elicited by MPP+. DNA ladder showed that typical DNA ladder was present in the MPP+ -induced SH-SY5Y cells. Additionally, MPP+ enhanced caspase-9 and caspase-3 ac tivity, respectively, while not caspase-8. However,the enhancement was concentration dependently blocked by puerarin pretreatment. Taken together, puerarin can modulate mitochondrial membrane potential and inhibit the cytochrome c releasing-caspase cascade to pre vent MPP+ -induced cell injury.


Subject(s)
Humans , 1-Methyl-4-phenylpyridinium , Pharmacology , Apoptosis , Blotting, Western , Caspase 3 , Metabolism , Caspase 8 , Metabolism , Caspase 9 , Metabolism , Cell Cycle , Cell Differentiation , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Isoflavones , Pharmacology , Membrane Potential, Mitochondrial , Mitochondria
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