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1.
Braz. j. biol ; 84: e255120, 2024. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1364532

ABSTRACT

This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, ß-carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.


O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do ß-caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.


Subject(s)
Rats , Plantago , Stomach Ulcer , Gastric Mucosa , Phytotherapy , Antioxidants
2.
Braz. J. Pharm. Sci. (Online) ; 58: e19194, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1383971

ABSTRACT

Abstract Increasing biological activity and phytochemical investigations on Eryngium species showed its potential as pharmaceutical approach. Eryngium kotschyi Boiss. is one of the species of Eryngium genus and is endemic to Turkey. It is known that this plant is traditionally used in the South-western part of Turkey for the treatment of various diseases. This study focuses on cytotoxic activities of methanol extract and ethyl acetate, n-butanol and water sub-extracts from E. kotschyi in A549, COLO 205 and MDA-MB-231 cell lines by Sulforhodamin B assay and qualitative and quantitative determination of phytochemical constituents in active extract by LC-MS/MS. From the result of the study, it was seen that E. kotschyi ethyl acetate (EKE) sub-extract showed the strongest cytotoxic effect with the low IC50 values (50.00; 31.96 and 22.26 μg/mL in A549; COLO 205 and MDA-MB-231 cells at 48 h, respectively). Preliminary examination of the mass spectrums revealed the presence of 15 phytochemical compounds in active sub-extract and 7 of them was quantified. According to quantitative analyses the main compounds of EKE sub-extract were rosmarinic acid (485.603 µg/mgextract), chlorogenic acid (62.355 µg/mgextract) and caffeic acid (59.266 µg/mgextract). Moreover, this preliminary study on inhibitory activity of EKE sub-extract suggests further toxicologic investigations and detailed investigation on cytotoxic effect of various combinations of determined compounds.

3.
Braz. J. Pharm. Sci. (Online) ; 58: e18957, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374547

ABSTRACT

Abstract The extract of Belamcanda chinensis leaves (BCLE) is a traditional Chinese herbal medicine for the treatment of diabetes-related hyperlipidemia in Hainan province, South China. In this study, the lipid-decreasing effects of BCLE on obese diabetes were investigated on KK-Ay mice. The component F2 ameliorated lipid disorder, as indicated by decreased levels of body weight, liver index, levels of TC, TG and LDL-c in the serum and liver. The enhancement effect of F2 on liver SOD and the inhibitory effect of F2 on MDA demonstrated that F2 exhibited significant antioxidant activity on liver injury. F2 also prevented vacuolar degeneration and reduced pathological tissue injury in liver. In addition, the component F1 decreased the levels of TG, LDL-c and MDA in the liver. These findings suggest that F2 may have therapeutic potential in the prevention and therapy of hyperlipemia and liver disease associated with obesity-related diabetes.

4.
Article in Chinese | WPRIM | ID: wpr-942775

ABSTRACT

Objective: To investigate the effect of piperine on human breast cancer cells. Methods: The effect of piperine on proliferation and migration of human breast cancer cells, MCF-7 and MDA-MB-231, was investigated using colony formation assays, wound healing assays, Matrigel migration assays, flow cytometry, RT-qPCR, and Western blotting assays. Results: Piperine inhibited the growth of MCF-7 and MDA-MB-231 cells and suppressed colony formation. Cell reduction at the G 0 / G 1 phase and cell arrest at the G 2 /M phase were observed in breast cancer cells. However, the significant effect was only demonstrated in MDA-MB-231 cells. Moreover, cancer cell migration was suppressed by piperine at low concentration. RT-qPCR and Western blotting assays showed that piperine downregulated Rac1 gene and protein expression. Conclusions: Piperine could inhibit growth and migration of breast cancer cells by reducing Rac1 gene and protein expression.

5.
Odovtos (En línea) ; 23(3)dic. 2021.
Article in English | LILACS-Express | LILACS, SaludCR | ID: biblio-1386553

ABSTRACT

ABSTRACT: Despite the reported effects of smokeless tobacco (ST) on the periodontium and high prevalence of ST use in rural populations and in males studies on this specific topic are limited. The purpose of this cross-sectional investigation was to measure lipid peroxidation (as an end product of oxidative stress) end product i.e. Malondialdehyde (MDA) in saliva of patients with gingivitis, chronic periodontitis and to assess the influence of smokeless tobacco on Salivary Malondialdehyde (S-MDA). Total 30 patients with gingivitis, 30 with chronic periodontitis and 30 Smokeless Tobacco Chewers with Chronic Periodontitis and 30 periodontally healthy subjects were included in the study. Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PD), and Clinical Attachment Loss (CAL) were recorded followed by stimulated Saliva sample collection. Salivary MDA Levels were assessed by UV Spectrophotometry. There was a statistically significant increase in the salivary MDA levels in gingivitis, chronic periodontitis and in smokeless tobacco chewers with chronic periodontitis when compared with healthy group. Higher salivary MDA levels in gingivitis group, chronic periodontitis, and smokeless tobacco chewers with chronic periodontitis reflects increasedoxygen radical activity during periodontal inflammation.


RESUMEN: A pesar de los efectos reportados del tabaco sin humo (TS) sobre el periodonto y la alta prevalencia del uso de TS en poblaciones rurales y en hombres, los estudios sobre este tema específico son limitados. El propósito de esta investigación transversal fue medir el producto final de la peroxidación lipídica (como producto final del estrés oxidativo), es decir, malondialdehído (MDA) en la saliva de pacientes con gingivitis, periodontitis crónica y evaluar la influencia del tabaco sin humo en el malondialdehído salival (S-MDA). Se incluyeron en el estudio un total de 30 pacientes con gingivitis, 30 con periodontitis crónica y 30 masticadores de tabaco sin humo con periodontitis crónica y 30 sujetos periodontalmente sanos. Se registraron el índice de placa (PI), el índice gingival (GI), la profundidad de la bolsa de sondeo (PD) y la pérdida de adherencia clínica (CAL), seguidos de la recogida de muestras de saliva estimuladas. Los niveles de MDA en saliva se evaluaron mediante espectrofotometría UV. Hubo un aumento estadísticamente significativo en los niveles de MDA en saliva en gingivitis, periodontitis crónica y en masticadores de tabaco sin humo con periodontitis crónica en comparación con el grupo sano. Los niveles más altos de MDA en saliva en el grupo de gingivitis, periodontitis crónica y masticadores de tabaco sin humo con periodontitis crónica reflejan un aumento de la actividad de los radicales de oxígeno durante la inflamación periodontal.


Subject(s)
Humans , Chronic Periodontitis/chemically induced , Tobacco Use , Lipid Peroxidation , Malondialdehyde/analysis
6.
Article in Chinese | WPRIM | ID: wpr-906110

ABSTRACT

Objective:To investigate the effect of piceatannol (PIC) on the proliferation, apoptosis and cell cycle of MDA-MB-468 triple negative breast cancer cells and its mechanism. Method:The methylthiazolyldiphenyl-tetrazoliu bromide (MTT) colcorimetry method was used to investigate the effect of different concentrations of PIC (0, 2.5, 5.0, 10.0, 20.0, 40.0, 80.0, 160.0 μmol·L<sup>-1</sup>) on the cell viabilities of triple negative breast cancer MDA-MB-468 cells and calculate the half maximal inhibitory concentration (IC<sub>50</sub>) value, the effect of different concentrations of PIC (5.0, 10.0, 20.0 μmol·L<sup>-1</sup>) on the cell cycle of MDA-MB-468 were investigated by flow cytometry with propidium iodide (PI) staining. The apoptotic effect of PIC (5.0, 10.0, 20.0 μmol·L<sup>-1</sup>) on MDA-MB-468 cells in triple negative breast cancer was investigated by flow cytometry with cell apoptosis detection Annexin V-FITC and PI double staining. Western blot was used to investigate the effect of different concentrations of PIC (5.0, 10.0, 20.0 μmol·L<sup>-1</sup>) on the proliferation and apoptosis of MDA-MB-468 cells and detect the expressions ofsecreted glycoprotein Wnt/<italic>β</italic>-catenin pathway related proteins. Result:MTT results showed that compared with the blank group, PIC could inhibit the proliferation of MDA-MB-468 cells in a concentration-dependent manner (<italic>P</italic><0.05, <italic>P</italic><0.01), with IC<sub>50</sub> at(39.4±4.6)μmol·L<sup>-1</sup>. Compared with the blank group, PIC could increase the percentage of MDA-MB-468 cells in G<sub>0</sub>/G<sub>1</sub> phase about cell cycle in a concentration-dependent manner (<italic>P</italic><0.01). Compared with the blank group, 5.0, 10.0, 20.0 μmol·L<sup>-1</sup> PIC could induce apoptosis of MDA-MB-468 cells for 48 h(<italic>P</italic><0.01), and the apoptosis rate of MDA-MB-468 cells reached 49.87% when treated with 20.0 μmol·L<sup>-1</sup> for 48 h. Compared with the blank group, PIC could significantly reduce the expressions of <italic>β</italic>-catenin, proto-oncogene (C-myc) and adhesion factor (CD44) proteins in MDA-MB-468 cells, significantly inhibit the phosphorylation of<italic> </italic>protein kinase B (Akt) and p38 mitogen activated protein kinase (p38 MAPK) proteins and the protein expression of B lymphocyte tumor-2 (Bcl-2), and enhance cysteine aspartic acid protease-3 (Caspase-3), Bcl-2 related X protein (Bax) and phosphorylated <italic>β</italic>-catenin protein expression(<italic>P</italic><0.01). Conclusion:PIC may inhibit the proliferation of MDA-MB-468 cells by inhibiting the Wnt/<italic>β</italic>-catenin signaling pathway, block the cell cycle in G0/G1 phase, and induce its apoptosis.

7.
Article in Chinese | WPRIM | ID: wpr-905898

ABSTRACT

Objective:To observe effect of Jingulian capsule on the proliferation of human breast cancer MDA-MB-231 cells and investigate its action mechanism against triple negative breast cancer (TNBC). Method:The ingredients of Jingulian capsule were identified by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). The inhibitory effect of Jingulian capsule at different doses (0.125,0.25,0.5,1,and 2 g·L<sup>-1</sup>) against the proliferation of MDA-MB-231 cells were detected by methyl thiazolyl tetrazolium (MTT) assay. After treatment for 24 h, the morphological changes in nuclear apoptosis of MDA-MB-231 cells were detected by Hoechst 33258 staining. The effect of different concentrations of Jingulian capsule on the apoptosis and cycle of MDA-MB-231 cells after different treatment time were determined by flow cytometry. The protein expression levels of Poly-ADP-ribose polymeras (PARP), proto-oncogene c-Myc, cyclin B<sub>1</sub>, and phosphorylated extracellular signal-regulated kinase (p-ERK) in each group were assayed by Western blot. Result:A total of 113 compounds in Jingulian capsule were identified by UPLC-MS/MS. As revealed by MTT assay,compared with blank group,Jingulian capsule (0.125,0.25,0.5,1,2 g·L<sup>-1</sup>) significantly inhibited viability of MDA-MB-231 cells (<italic>P</italic><0.01), with the half maximal inhibitory concentration ( IC<sub>50</sub>) of(0.13±0.02)g·L<sup>-1</sup>. According to flow cytometry,compared with the blank group,Jingulian capsule at 1 g·L<sup>-1</sup> significantly induced the apoptosis of MDA-MB-231 cells (<italic>P</italic><0.05)and Jingulian capsule at 0.5, 1 g·L<sup>-1</sup> obviously increased the number of MDA-MB-231 cells in S phase (<italic>P</italic><0.05,<italic>P</italic><0.01). The results of Western blotting demonstrated that the protein expression levels of PARP,c-Myc,and cyclin B<sub>1</sub> in 0.5, 1 g·L<sup>-1 </sup>Jingulian capsule groups were remarkably down-regulated as compared with those in the blank group(<italic>P</italic><0.01), and the protein expression level of p-ERK in 1 g·L<sup>-1 </sup>Jingulian capsule group was also down-regulated (<italic>P</italic><0.01). Conclusion:Jingulian capsule is able to inhibit the proliferation of MDA-MB-231 cells,induce S phase cell cycle arrest, and promote their apoptosis, which may be related to the inactivation of the MAPK signaling pathway.

8.
Article in Chinese | WPRIM | ID: wpr-905832

ABSTRACT

Objective:To confirm the protective effect of Xiangsha Yuyang decoction on acetic acid-induced gastric ulcer model rats and explore its mechanism, so as to provide experimental basis for clinical drug use. Method:The 60 SPF Wistar rats were randomly divided into 6 groups: group, model group, high, middle and low dose groups of Xiangsha Yuyang decoction and omeprazole control group. The rat model of gastric ulcer was induced by acetic acid. The rats in the high, middle and low dose groups of Xiangsha Yuyang decoction were intragastrically administered at the dose of 28,14,7 g·kg<sup>-1</sup>, and with omeprazole at the dose of 4.17 g·kg<sup>-1</sup>in normal saline, respectively. The rats in the blank group and model group were intragastrically infused with the same volume of normal saline once a day. After 14 days of continuous treatment, the rats were killed, the blood was collected, the area and inhibition rate of gastric ulcer were measured and calculated, the histopathological sections of gastric mucosa were made and the state of gastric mucosal injury was observed, and the changes of gastric mucosal repair factor, gastric tissue related protein, oxidative stress factor and inflammatory factor in serum were detected by enzyme-linked immunosorbent assay(ELISA). Detected the expression of p62 Kelch-like epichlorohydrin-related protein 1 (Keap1), nuclear transcription factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) signal pathway-related proteins in gastric mucosa by Western blot. Result:Compared with control group, the gastric mucosa of the model group showed obvious pathological changes and a large number of leukocytes infiltrated. In model group, the ulcer area was significantly increased(<italic>P</italic><0.01), the contents of mucin mucoprotein 5AC (MUC5AC), epidermal growth factor (EGF), superoxide dismutase (SOD) and increased prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) were significantly decreased(<italic>P</italic><0.01), the gastrin (GAS), 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), cyclooxygenase-2 (COX-2) were significantly increased. The expression of HO-1 and Nrf2 protein decreased significantly(<italic>P</italic><0.01), the content of Keap1 increased significantly (<italic>P</italic><0.05), and the expression of p62 protein decreased. Compared with model group, the hierarchical structure of cells in Xiangsha Yuyang decoction high dose group and omeprazole group were clearer and regular, middle and low dose groups could also repair gastric mucosa to a certain extent. The high and middle dose groups of Xiangsha Yuyang decoction could significantly reduce the gastric ulcer area of acetic acid-induced gastric ulcer rat model (<italic>P</italic><0.01) and increase the ulcer inhibition rate. It can effectively promote the expression of MUC5AC and EGF in gastric mucosa, decrease the level of GAS(<italic>P</italic><0.05,<italic>P</italic><0.01), decrease the level of 8-OHdG and MDA, increase the activity of SOD(<italic>P</italic><0.01), decrease the expression level of TNF-<italic>α</italic> and COX-2, increase the content of PGE<sub>2</sub>, and significantly increase the amount of Nrf2 and HO-1 protein in gastric mucosa(<italic>P</italic><0.01). The high dose group of Xiangsha Yuyang decoction could decrease the protein expression of Keap1(<italic>P</italic><0.05) and increase the expression of p62 protein. Conclusion:Xiangsha Yuyang decoction is effective in the treatment of acetic acid-induced gastric ulcer model rats, which can effectively reduce the ulcer area, increase the ulcer inhibition rate and protect the ulcer tissue. Its mechanism may be related to activating p62/Keap1/Nrf2 signal pathway and regulating the expression of related genes so as to improve inflammatory response and regulate oxidative stress response.

9.
Article in Chinese | WPRIM | ID: wpr-904335

ABSTRACT

@#The aim of this study was to investigate the effect of transmembrane 9 superfamily protein member 2 (TM9SF2) in proliferation and migration of triple negative breast cancer cell line MDA-MB-231.The expression of TM9SF2 in triple negative breast cancer cell line MDA-MB-231 and nontumorigenic mammary epithelial cell line MCF-10A were measured by Western blot. MDA-MB-231 cells were treated with siRNA-TM9SF2 to knock-down the expression of TM9SF2. The effect of silencing TM9SF2 was measured with Western blot.The proliferation of cells was tested by MTS,and the migration was measured with Transwell and wound-healing assay.Proteins related to proliferation (PI3K,AKT,SRC and ERK) and migration (Snail,Slug and N-cadherin) were measured with Western blot.Protein expressions of TM9SF2 was better improved in triple negative breast cancer MDA-MB-231 cell line than MCF-10A.Compared with the control group, the siRNA-TM9SF2 infected group had lower expressions of PI3K, Snail, Slug and N-cadherin, and at the same time phosphorylation of AKT was decreased. The results suggest TM9SF2 can promote the proliferation and metastasis of triple negative breast cancer MDA-MB-231 cell line.

10.
Article in Chinese | WPRIM | ID: wpr-887413

ABSTRACT

@#[摘 要] 目的:探讨大荨麻提取物对乳腺癌细胞增殖、凋亡和细胞周期的影响,并初步探讨其可能的作用机制。方法:用不同质量浓度的大荨麻提取物(0、1、2、4、8、16、32、64 mg/ml)处理乳腺癌细胞MCF-7和MDA-MB-231 24 h,MTT法检测细胞增殖活力,选择中位抑制浓度附近的浓度(5和10 mg/ml)作为给药浓度分别处理MCF-7和MDA-MB-231细胞24 h后,平板克隆形成实验和流式细胞术分别检测大荨麻提取物对乳腺癌细胞增殖、周期和凋亡的影响,WB法检测对细胞周期和凋亡相关蛋白以及PI3K/AKT信号通路相关蛋白表达的影响。在MCF-7细胞用5 mg/ml大荨麻提取物处理的同时转染过表达AKT质粒(大荨麻+AKT组),转染空载质粒为对照组(大荨麻+vec组),WB法检测过表达效率,比较过表达AKT对细胞增殖、周期和凋亡的影响。结果:各大荨麻提取物处理组MCF-7和MDA-MB-231细胞增殖活力均显著低于对照组(P<0.05或P<0.01);与对照组比较,5或10 mg/ml大荨麻处理组乳腺癌细胞的克隆形成数显著减少,G0/G1期细胞占比和凋亡率显著增加(P<0.05或P<0.01),P21、BAX蛋白表达显著升高而Cyclin D1、CDK4、Bcl2蛋白以及p-PI3K、p-AKT蛋白表达显著降低(P<0.05或P<0.01)。大荨麻+AKT组p-AKT和AKT蛋白表达显著高于大荨麻+vec组,克隆数、S期和G2/M期细胞占比均高于大荨麻+vec组(P<0.05或P<0.01),G0/G1期细胞占比和凋亡率低于大荨麻+vec组(P<0.05或P<0.01)。结论:大荨麻提取物可以抑制乳腺癌细胞增殖、促进凋亡且阻滞细胞在G0/G1期,其作用机制可能与抑制PI3K/AKT信号通路相关。

11.
Organ Transplantation ; (6): 571-2021.
Article in Chinese | WPRIM | ID: wpr-886786

ABSTRACT

Objective To evaluate the effect of mild hypothermia on the renal ischemia-reperfusion injury (IRI), and the expression profile of RNA-binding motif protein 3(RBM3) and its downstream effector molecules during this process. Methods Eighteen healthy SD male rats were randomly divided into the normal control (NC) group, IRI group and mild hypothermia pretreat (MHP) group, with 6 rats in each group. Serum creatinine level was measured to evaluate the renal function. Hematoxylin-eosin (HE) staining was performed to assess the renal tissue injury. Western blot was used to determine the relative expression levels of RBM3, Yes-associated protein 1(YAP1), nuclear factor E2-related factor 2(Nrf2), B cell-lymphoma-2(Bcl-2) and Bcl-2-associated X protein (Bax) in the kidney tissues. Immunohistochemical staining was employed to further detect the expression levels of RBM3 and YAP1 proteins. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was adopted to detect the cell apoptosis of kidney tissues. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were evaluated to determine the oxidative stress level of kidney tissues. Results Compared with the NC group, the serum creatinine level, the pathological injury score of kidney tissues and the expression levels of RBM3, YAP1 and Nrf2 proteins were significantly up-regulated, the Bcl-2/Bax ratio was considerably lower, the apoptosis rate was remarkably elevated, the MDA content was significantly increased and the SOD activity was dramatically reduced in the IRI and MHP groups (all P < 0.05). Compared with the IRI group, the serum creatinine level and the pathological injury score of kidney tissues were significantly decreased, the expression levels of RBM3, YAP1 and Nrf2 proteins were significantly up-regulated, the Bcl-2/Bax ratio was considerably higher, the apoptosis rate was significantly decreased, the MDA content was significantly decreased and the SOD activity was considerably elevated in the MHP group (all P < 0.05). Conclusions Mild hypothermia may exert protective effect upon renal IRI and it could alleviate cell apoptosis and oxidative stress injury induced by IRI, probably by up-regulating the expression level of RBM3 and its downstream effector molecules of YAP1 and Nrf2.

12.
Article in Chinese | WPRIM | ID: wpr-886474

ABSTRACT

@#[摘 要] 目的:探讨紫甘薯花色苷(purple sweet potato anthocyanin, PSPA)是否通过circ_0003998/miR-145轴调控乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。方法:选用乳腺癌MDA-MB-231细胞,将其分为对照组,200、400和800 μg/ml PSPA组,pcDNA组、pcDNA-circ_0003998组、si-NC组、si-circ_0003998组、si-circ_0003998+anti-miR-145组、PSPA+pcDNA组、PSPA+pcDNA-circ_0003998组和PSPA+anti-miR-145组。用qPCR法检测细胞中circ_0003998和miR-145的表达,CCK-8法、Transwell小室法分别检测转染前后细胞的增殖、迁移和侵袭能力,WB法检测细胞中Ki-67、MMP-2和MMP-9蛋白的表达。用双荧光素酶报告基因实验验证circ_0003998与miR-145的靶向关系。结果:与对照组比较,各剂量PSPA组MDA-MB-231细胞的增殖抑制率、miR-145表达水平均显著升高(均P<0.01),Ki-67、MMP-2、MMP-9蛋白和circ_0003998的表达水平、细胞迁移和侵袭细胞数均显著降低(均P<0.01),并呈现浓度依赖性。circ_0003998可以靶向负调控miR-145的表达。敲减circ_0003998后,MDA-MB-231细胞的增殖抑制率、miR-145表达水平显著升高,Ki-67、MMP-2和MMP-9蛋白表达水平、细胞迁移和侵袭细胞数均显著减少(均P<0.01)。共转染si-circ_0003998和anti-miR-145则可逆转敲减circ_0003998表达对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用,过表达circ_0003998或抑制miR-145表达可逆转PSPA对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用。结论:PSPA通过circ_0003998/miR-145轴抑制乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。

13.
China Pharmacy ; (12): 1848-1853, 2021.
Article in Chinese | WPRIM | ID: wpr-886278

ABSTRACT

OBJECTIVE:To study the effects of Plantago asiatica polysaccharide on the proliferation ,migration and invasion of breast cancer cells ,and to investigate its mechanism preliminarily. METHODS :Using human breast cancer cell MDA-MB- 231 as subjects ,MTT method was adopted to detect the effects of different concentrations of P. asiatica polysaccharide(8,16,32,64 mg/L)on the cell proliferation ability ,and survival rate of the cells was calculated. Scratch test and Transwell invasion test were used to detect the effects of different concentrations of P. asiatica polysaccharide(8,16 mg/L)on cell migration ability and invasion ability. Western blot assay was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins [matrix metalloproteinase- 2(MMP-2),MMP-9,E-cadherin,N-cadherin,vimentin]. RESULTS :Results of MTT assay showed that survival rate of the cells in 32,64 mg/L P. asiatica polysaccharide groups were significantly lower than control group (P<0.05 or P<0.01),so that 8,16 mg/L,which did not affect the cell survival rate ,were used as the follow-up drug concentrations. Compared with control group ,relative mobility (12,24 h),relative invasion rate and relative expression of MMP- 2,MMP-9, N-cadherin and vimentin protein were decreased significantly in 8,16 mg/L P. asiatica polysaccharide groups (P<0.05 or P< 0.01),while relative expression of E-cadherin protein was increased significantly (P<0.05 or P<0.01). CONCLUSIONS :P. asiatica polysaccharide can inhibit the proliferation of breast cancer cells MDA-MB- 231,and inhibit the migration and invasion of the cells by regulating the expression of metastasis and EMT-related proteins.

14.
Acta Pharmaceutica Sinica B ; (6): 1341-1354, 2021.
Article in English | WPRIM | ID: wpr-881203

ABSTRACT

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

15.
Acta Pharmaceutica Sinica B ; (6): 1400-1411, 2021.
Article in English | WPRIM | ID: wpr-888811

ABSTRACT

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.

16.
Article in Chinese | WPRIM | ID: wpr-877563

ABSTRACT

OBJECTIVE@#To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).@*METHODS@#A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared.@*RESULTS@#Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (@*CONCLUSION@#Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.


Subject(s)
Acupuncture Therapy , Blood Glucose , Female , Glucose , Glucose Intolerance/therapy , Humans , Insulin , Insulin Resistance , Polycystic Ovary Syndrome/therapy
17.
Article in Chinese | WPRIM | ID: wpr-906395

ABSTRACT

Objective:To investigate the effects of curdione on the proliferation, apoptosis and cell cycle of triple negative breast cancer cell line MDA-MB-231. Method:MDA-MB-231 cells were cultured<italic> in vitro</italic> with capecitabine (positive control) and curdione at different concentrations (125, 250, 500, 1 000, and 2 000 μmol·L<sup>-1</sup>), respectively, for detecting their viability using the cell counting kit-8 (CCK-8) at 24 and 48 h. Three effective inhibitory concentrations (250, 500, and 1 000 μmol·L<sup>-1</sup>) against cell proliferation were selected for subsequent experiments. The effect of curdione on cell cycle was determined by flow cytometry combined with propidium iodide (PI) staining. After the set-up of high-concentration (2 000 μmol·L<sup>-1</sup>) group, the effect of curdione on cell mitochondrial membrane potential was measured by JC-1(5,5,6,6-tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide) staining, followed by the detection of cell apoptosis by flow cytometry combined with Annexin V-FITC/PI double staining. The changes in cell cycle status and apoptosis-related protein expression following curdione intervention were assayed by Western blot. Result:Compared with the blank control, curdione at 250, 500, 1 000, and 2 000 μmol·L<sup>-1 </sup>significantly inhibited the proliferation of MDA-MB-231 cells (<italic>P</italic><0.01), exhibiting a concentration- and time-response relationship. The half maximal inhibitory concentration (IC<sub>50</sub>) values at 24 and 48 h were 1 607 and 1 401 μmol·L<sup>-1</sup>, respectively. Curdione at 250, 500, and 1 000 μmol·L<sup>-1</sup> arrested cells in G<sub>1</sub> phase. Curdione at 250 μmol·L<sup>-1 </sup>had no effect on cell mitochondrial membrane potential, which, however, declined significantly in the 500, 1 000, and 2 000 μmol·L<sup>-1 </sup>groups (<italic>P</italic><0.05, <italic>P</italic><0.01). Curdione at 250, 500, and 1 000 μmol·L<sup>-1 </sup>obviously increased the proportion of apoptotic cells (<italic>P</italic><0.05, <italic>P</italic><0.01). Curdione at each concentration elevated the Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio (<italic>P</italic><0.05, <italic>P</italic><0.01), but did not change the cysteinyl aspartate-specific protease-3 (Caspase-3) expression. The protein expression levels of Caspase-9, cleaved Caspase-9, cleaved Caspase-3, p53, and p21 were up-regulated (<italic>P</italic><0.05). Conclusion:A certain concentration of curdione inhibits the proliferation of MDA-MB-231 cells, which may be related to its efficacy in arresting cell cycle and inducing apoptosis.

18.
Article in Chinese | WPRIM | ID: wpr-906358

ABSTRACT

Objective:To study the efficacy and mechanism of Shugan Jianpi Jiedu prescription (SJJ) in the treatment of triple-negative breast cancer through <italic>in vitro</italic> cell experiments. Method:The following groups were set up in this study: a normal serum group,a pirarubicin group,and low-,medium-, and high-dose SJJ-medicated serum groups. Twenty SD rats were randomly divided into four groups and administered with SJJ solution (16.8,8.2,4.05 g·kg<sup>-1</sup>) and normal saline (equal volume) according to the body surface area to prepare serum. MDA-MB-231 cells were treated separately. The proliferation, migration and invasion of MDA-MB-231 cells were detected by the cell counting kit-8(CCK-8),wound healing assay and transwell cell invasion assay. The phosphoinositide 3-kinase (PI3K),protein kinase B (Akt), and mechanistic target of rapamycin (mTOR) protein expression levels in MDA-MB-231 cells were tested by the Western blot. Result:The cell proliferation in the three different doses of medicated serum groups and the pirarubicin positive control group was significantly inhibited as compared with that in the normal serum group(<italic>P</italic><0.01),and there was no statistical difference for this between the medium/high dose medicated serum group and the pirarubicin positive control group.The wound healing in the SJJ-medicated serum groups and the pirarubicin group was slowed down as compared with that in the normal serum group (<italic>P</italic><0.01),and the effect in the SJJ-medicated serum groups was weaker than that in the pirarubicin group (<italic>P</italic><0.05,<italic>P</italic><0.01). The number of cells invading the lower transwell chamber was decreased as compared with that in the normal serum group (<italic>P</italic><0.01),and there was no statistical difference between the medium-/high-dose SJJ-medicated serum groups and the pirarubicin group. Western blot results showed that 48 h after treatment,the PI3K,Akt, and mTOR expression levels in the cells of SJJ-medicated serum groups and the pirarubicin group were lower than those of the normal serum group(<italic>P</italic><0.01). Conclusion:The SJJ-medicated serum could inhibit the proliferation, migration and invasion of MDA-MB-231 cells presumedly by down-regulating the protein expression levels in the PI3K/Akt/mTOR signaling pathway.

19.
Article in Chinese | WPRIM | ID: wpr-942824

ABSTRACT

Objective: To determine the effect of climatic and environmental factors on the incidence of cutaneous leishmaniasis in Qom province in 2018. Methods: In this cross-sectional study, the data on cutaneous leishmaniasis incidence were collected from the Disease Control and Prevention Center in Qom province. Climatic and environmental data including Normalized Difference Vegetation Index (NDVI), Land Surface Temperature (LST), and soil moisture were extracted using satellite images. Data of altitude and sunny hours were provided based on shuttle radar topography mission digital elevation model and hemispherical viewshed algorithm, respectively. The associations of climatic and environmental variables with the incidence of the disease were analyzed by Pearson correlation method. The ArcGIS 10.3 software was used to determine the geographical distribution of these factors. Results: There were positive correlations between cutaneous leishmaniasis incidence and the two climatic factors: LST and sunny hours per day (P=0.041, P=0.016), and it had weak negative correlations with the digital elevation model (P=0.27), soil moisture (P=0.54), and NDVI (P=0.62). The time delay analysis showed that in one-, two-, and three month periods, the correlations increased with a 95% confidence interval. Accordingly, the correlation with the three-month time delay was positive and relatively strong between the cutaneous leishmaniasis incidence and LST and sunny hours (P=0.027, P=0.02); nevertheless, there were negative correlations between the cutaneous leishmaniasis incidence and the soil moisture (P=0.27) and NDVI (P=0.62). Conclusions: As Qom is located in one of the semi-arid climate zones, topography and solar energy are important factors affecting the incidence of cutaneous leishmaniasis in autumn. Therefore, appropriate disease control programs are recommended.

20.
Article in Chinese | WPRIM | ID: wpr-942823

ABSTRACT

Objective: To evaluate the immunostimulatory potential of cross-reactive molecule heat shock protein 60 (HSP60) of filarial parasite Brugia malayi and Leishmania donovani. Methods: HSP60 of Brugia malayi (BmHSP60) was amplified using gene-specific primer, cloned in pTriEx4 vector, expressed in BL21-DE3 cells, and recombinant HSP60 (rHSP60) of 65 kDa was purified by affinity chromatography using Ni-NTA column. The recombinant protein was desalted by the dialysis membrane, and the presence of endotoxin level was determined by Limulus amebocyte lysate assay. The recombinant protein was tested for cell proliferation, nitric oxide release, expression of Th1 and Th2 cytokines, and transcription factors (STATs) in vitro using murine macrophage cell line (J774A.1). Results: Higher cell proliferation indicated that BmHSP60 had immunostimulatory potential. rBmHSP60 exposure upregulated the expression of iNOS, STAT1, STAT4, Th1 cytokines (IFN-γ, TNF-α, IL-12), and nitric oxide release. In addition, no remarkable change was observed in the expression of IL-6, IL-10, and STAT3 in macrophage cell line J774A.1. The ELISA analysis showed the levels of IFN-γ, TNF-α, and IL-12 were upregulated while IL-10 level was downregulated, revealing that BmHSP60 triggered a Th1 immune response. Conclusions: Our study demonstrates that rBmHSP60 has immunogenic properties which effectively enhances the Th1 type immune responses, and can be used as an immunoprophylactic agent against leishmaniasis. Furthermore, in vivo studies are in progress to determine the protective role of rBmHSP60 against Leishmania donovani infection in a mouse model.

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