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1.
Article in Chinese | WPRIM | ID: wpr-928725

ABSTRACT

OBJECTIVE@#To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia (B-ALL) cells to Vincristine (VCR) and the mechanisms.@*METHODS@#B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and β-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and β-actin mRNA levels.@*RESULTS@#CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups.@*CONCLUSION@#Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX.


Subject(s)
Actins/pharmacology , Apoptosis , Cell Hypoxia , Humans , Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit , Proto-Oncogene Proteins c-bcl-2 , RNA, Messenger , Vincristine/pharmacology , bcl-2-Associated X Protein/pharmacology
2.
Chinese Journal of Neurology ; (12): 1119-1127, 2021.
Article in Chinese | WPRIM | ID: wpr-911845

ABSTRACT

Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.

3.
Article in Chinese | WPRIM | ID: wpr-906478

ABSTRACT

Objective:To observe the effect of Wuzi Yanzong Wan made of different processed products on the apoptosis of spermatogenic cells in rats with kidney essence deficiency, and explore its protective effect on spermatogenic cells. Method:SD rats were randomly divided into the blank group, model group, whole raw product group, pharmacopoeia group and salt-processed product group, with 8 rats in each group. The kidney essence deficiency model was replicated by giving tripterygium glycoside tablets (the dose of 20 mg·kg<sup>-1</sup>). The flow cytometry (FCM) was used to analysis the apoptosis of spermatogenic cells in testis, the immunohistochemistry (IHC) and Western blot were used to detect the expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the testis. High performance liquid chromatography (HPLC) was used to compare the contents of eight components (chlorogenic acid, ellagic acid, hyperoside, isoquercitrin, verbascoside, astragalin, kaempferol and schisandrin) in Wuzi Yanzong Wan made of different processed products, the mobile phase was composed of acetonitrile (A)-0.4% phosphoric acid aqueous solution (B) for gradient elution (0-5 min, 5%-15%A; 5-10 min, 15%-17%A; 10-25 min, 17%A; 25-35 min, 17%-26%A; 35-60 min, 26%-56%A), the detection wavelength was set at 254 nm. Result:Compared with the model group, the total apoptosis rate of spermatogenic cells, protein expression of Bax and Bcl-2 in each administration group were improved. Among them, the pharmacopoeia group and salt-processed product group had significant effects (<italic>P</italic><0.01), and the improvement effect of the pharmacopoeia group and salt-processed product group was significantly better than that of the whole raw product group (<italic>P</italic><0.05). The contents of chlorogenic acid, hyperoside, isoquercitrin and verbascoside in Wuzi Yanzong Wan were increased after the herbal medicines being processed with salt-water. The content of ellagic acid in the salt-processed product group increased, while it decreased in the pharmacopoeia group. The contents of verbascoside, astragalin, kaempferol and schisandrin in samples from the salt-processed product group were greater than those in samples from the pharmacopoeia group. Conclusion:Wuzi Yanzong Wan may reduce the apoptosis of spermatogenic cells in rat testis by inhibiting the expression of Bax and promoting the expression of Bcl-2, and exert its effect of nourishing kidney and enriching essence. The enhanced anti-spermatogenic effect of Wuzi Yanzong Wan after processing may be related to the changes in chemical composition content after processing.

4.
Article in Chinese | WPRIM | ID: wpr-906052

ABSTRACT

Objective:To investigate the effect of<italic> Stemona tuberosa</italic> alkaloids on the apoptosis of human hepatoma SMMC-7721 cells and the expression of apoptosis-related proteins including B lymphocytoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved cysteinyl aspartate-specific protease-3 (cleaved Caspase-3). Method:SMMC-7721 cells were routinely cultured, passaged, and treated with various concentrations (50, 75, 112, 167, and 250 mg·L<sup>-1</sup>) of <italic>S. tuberosa </italic>alkaloids, while those in the blank control group were only treated with 10% fetal bovine serum. The cell proliferation was determined by tetrazolium bromide (MTT) colorimetry and colony assay and the cell apoptosis by Hoechst 33258 staining. The protein expression levels of Bcl-2, Bax, and cleaved Caspase-3 were detected by Western blot. Result:<italic>S. tuberosa</italic> alkaloids inhibited the proliferation of SMMC-7721 cells, and the inhibition rate was significantly increased in comparison with that in the blank control group (<italic>P</italic><0.01), with the half maximal inhibitory concentrations (IC<sub>50</sub>) at 24 h, 48 h, and 72 h being (173.36±8.75), (112.14±16.50), and (96.41±2.60)mg·L<sup>-1</sup>, respectively. The cell colony-inhibitory activity was significantly increased in a dose-dependent manner (<italic>P</italic><0.01). Compared with the blank control group, <italic>S. tuberosa</italic> alkaloids promoted the apoptosis of SMMC-7721 cells, manifested as increased number of apoptotic cells and elevated apoptotic rate (<italic>P</italic><0.01). The typical morphological changes such as brightly blue-fluorescent condensed nuclei, cytoplasmic shrinking, and karyopyknosis were found under the upright fluorescence microscope. As revealed by comparison with the blank control group, the expression of Bcl-2 was significantly down-regulated (<italic>P</italic><0.01), while the protein expression levels of pro-apoptotic protein Bax and cleaved Caspase-3 in the 75, 112, 167, and 250 mg·L<sup>-1</sup> <italic>S. tuberosa</italic> alkaloids groups were significantly up-regulated (<italic>P</italic><0.01). Conclusion:<italic>S. tuberosa </italic>alkaloids inhibit the proliferation of SMMC-7721 cells and promote their apoptosis possibly by inhibiting Bcl-2 protein expression and promoting Bax and cleaved Caspase-3 protein expression.

5.
Tropical Biomedicine ; : 53-62, 2021.
Article in English | WPRIM | ID: wpr-904534

ABSTRACT

@#Background: toxoplasmosis is a cosmopolitan protozoan disease with a wide range of neuropathology. Recent studies identified its potential association with several mental disorders e.g. schizophrenia dependable on apoptosis in their pathogenesis. We investigated value of toxoplasmosis to induce apoptosis of the neuronal cells. Methods: per-orally infected C57BL/6 mice with 15-20 cysts of the avirulent T. gondii Beverly strain at 9-11 weeks of age were examined 12 weeks later during parasite establishment. Distributions of the parasite’s cysts and the histopathological lesions in the brains were analyzed using Image J software. Relative expression of TNF-α and iNOS of cell-mediated immunity (CMI), Bax (pro-apoptosis) and Bcl-2 (anti-apoptosis) were all assessed using immunohistochemistry. Results: higher parasite burden was seen in the forebrain with p value < 0.05. Dramatically increased TNF-α, iNOS, and Bax expressions with Bax/Bcl-2 ratio 2.42:0.52 were reported (p value < 0.05). The significant correlation between Bax data and different CMI biomarkers including TNF-α and i-NOS was evaluated. Interestingly, no significant correlation was seen between TNF-α, iNOS, Bax and Bcl-2 expressions and location of the parasite. However, Bax/Bcl-2 ratio was statistically correlated with CMI biomarkers and whole sample mean parasite burden, p value < 0.05. Conclusion: Chronic toxoplasmosis exhibits an immense pro-apoptotic signal on the cerebral tissues of experimental mice.

6.
Article in Chinese | WPRIM | ID: wpr-883515

ABSTRACT

Parkinson's disease(PD)is the second most common neurodegenerative disease in the world;however,it lacks effective and safe treatments.Ginkgo biloba dropping pill(GBDP),a unique Chinese G.biloba leaf extract preparation,exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD.Thus,the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G.biloba extract EGb 761.Using liquid chromatography tandem-mass spectrometry,46 GBDP constitu-ents were identified.Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761.A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761,whereas EGb 761 had higher levels of organic acids.Moreover,we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice.Although similar effects were observed after EGb 761 treatment,the neuroprotective effects were greater after GBDP treatment on several endpoints.In addition,in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP.These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

7.
Article in Chinese | WPRIM | ID: wpr-921809

ABSTRACT

The present study investigated the effect of Modified Dihuang Decoction in improving ovarian reserve in mice through the Bcl-2-related mitochondrial apoptosis pathway. Forty-eight adult female BALB/c mice were randomly divided into the following six groups with eight mice in each group: a blank group, a model group, a femoston group(three cycles of treatment with 0.13 mg·kg~(-1) estradiol tablets for 2 days and 1.43 mg·kg~(-1) estradiol and dydrogesterone tablets for 3 days), and high(64.74 g·kg~(-1))-, medium(43.16 g·kg~(-1))-, and low-dose(21.58 g·kg~(-1)) Modified Dihuang Decoction groups. Mice in other groups except the blank group received a single intraperitoneal injection of 12 mg·kg~(-1) cyclophosphamide and 1.2 mg·kg~(-1) busulfan to induce a model of diminished ovarian reserve(DOR), while those in the blank group received an equal volume of normal saline. Mice were treated with corresponding drugs for 15 d from the 36 th day, once per day, and the mice in the blank group and the model group were treated with an equal volume of normal saline. The general condition and oestrous cycle were observed. The serum hormone levels were detected with the enzyme-linked immunosorbent assay(ELISA). The morphological changes of ovaries were observed by HE staining. Western blot was used to detect the protein expression of cysteinyl aspartate specific proteinase-9(caspase-9), cleaved caspase-3, Bcl-2 associated X protein(Bax), Bcl-2, superoxide dismutase-2(SOD-2), and glutathione peroxidase-1(GPx-1). The mRNA expression of Bax and Bcl-2 was detected by real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR). The results showed that compared with the blank group, the model group showed body weight loss, disordered oestrous cycle, elevated serum levels of follicle-stimulating hormone(FSH) and luteinizing hormone(LH), reduced serum levels of estradiol(E_2), anti-mullerian hormone(AMH), and inhibin B(INHB), the declining number of ovarian follicles and granulosa layers, increased number of atretic follicles, up-regulated protein expression of caspase-9, cleaved caspase-3, and Bax and Bax mRNA expression in ovaries, and down-regulated protein expression of Bcl-2, SOD-2 and GPx-1, and Bcl-2 mRNA expression. Compared with the model group, the Modified Dihuang Decoction groups displayed restored body weight and oestrous cycle, decreased serum levels of FSH and LH, elevated serum levels of E_2, AMH, and INHB, increased number of ovarian follicles, thickened granulosa layers, and declining number of atretic follicles. Additionally, the protein expression of caspase-9, cleaved caspase-3, and Bax, and Bax mRNA expression was down-regulated, and the protein expression of Bcl-2, SOD-2, and GPx-1, and Bcl-2 mRNA expression was up-regulated. The results suggest that Modified Dihuang Decoction can regulate endocrine hormone, promote follicle growth and improve ovarian reserve by enhancing ovarian anti-oxidant capacity, inhibiting the Bcl-2-related mitochondrial apoptosis pathway, and further inhibiting cell apoptosis.


Subject(s)
Animals , Apoptosis , Female , Mice , Mice, Inbred BALB C , Ovarian Follicle , Ovarian Reserve , Ovary
8.
Article in Chinese | WPRIM | ID: wpr-876706

ABSTRACT

Objective To investigate the expression and clinicopathological significance of Bcl-2 and Bax genes in colorectal cancer (CRC) patients complicated with schistosomiasis. Methods The CRC patients receiving surgical treatment in the First Affiliated Hospital of Dali University from June 2016 to June 2020 were recruited as the study subjects, and 30 subjects were randomly sampled from the CRC patients complicated with schistosomiasis (CRC-S group) and 30 subjects were randomly sampled from the CRC patients without schistosomiasis (CRC group) using a random number table method. The cancer specimens were sampled from subjects in the CRC-S and CRC groups, and the peri-cancer specimens were sampled from subjects in the CRC group. The Bcl-2 and Bax expression was quantified in cancer and peri-cancer specimens using a real-time fluorescent quantitative PCR (qPCR) assay and immunohistochemistry at transcriptional and translational levels, and the cell apoptosis was detected in cancer specimens using HE staining. Results A total of 60 subjects were enrolled, including 30 cases in the CRC group and 30 cases in the CRC-S group. There were no significant differences between the two groups in terms of gender distribution (χ2 = 0.271, P > 0.05), mean age (t = -0.596, P > 0.05), tumor growth pattern (χ2 = 0.275, P > 0.05), tumor location (χ2 = 4.008, P > 0.05), tumor invasion depth (χ2 = 0.608, P > 0.05), degree of tumor differentiation (χ2 = 0.364, P > 0.05), or presence of vascular metastasis (χ2 = 1.111, P > 0.05), while significant differences were seen between the two groups in terms of histological type, presence of lymph node metastasis and TMN staging (χ2 = 5.963, 8.297 and 5.711, all P values < 0.05). qPCR assay and immunohistochemistry quantified significantly higher Bcl-2 and Bax expression in cancer specimens from the CRC and CRC-S groups than in the peri-cancer specimens from the CRC group at both translational and transcriptional levels (all P values < 0.05), and higher Bcl-2 and lower Bax expression were seen in the cancer specimens from the CSC-S group than that from the CRC group (all P values < 0.05). In addition, the cell apoptotic rate was significantly greater in the cancer specimens in the CRC group than in the CRC-S group (42.00% vs. 23.35%; χ2 = 41.500, P = 0.000). Conclusion Schistosomiasis may be involved in the development and progression of CRC through affecting Bcl-2 and Bax gene expression in the apoptosis signaling pathway.

9.
Int. j. morphol ; 38(2): 427-434, abr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056458

ABSTRACT

Granulosa cells (GCs) are essential components of follicles and play a role in regulating follicle development. The aim of this study was to investigate certain cellular components involved in the proliferation, differentiation and functional characteristics of granulosa cells in the success of fertilization of human oocytes during invitro fertilization (IVF) via immunohistochemical techniques. In this study, 30 patients who were diagnosed as primary or secondary infertility, polycystic ovary syndrome in the IVF center of Memorial Hospital, Department of Obstetrics and Gynecology were included. The amount of Anti Müllerian Hormone (AMH) in blood and granulosa cell diameter and cell core diameter were measured in 20 cells collected from each patient. In addition, degeneration scoring and BAX, ADAMTS-1, IL-10 expressions in granulosa cells were evaluated (p <0.01). It was thought that apoptosis induced by human GCs might be an indicator of egg quality. Moderate expression of ADAMTS-1 was thought to be related to failure of ovulation, deterioration of oocyte quality and decreased fertilization rate. This decrease in AMH levels may be associated with defects in granulosa cells. Therefore, significantly lower AMH secretion and increase in IL10 expression levels in healthy people can be explained by the increase of granulocyte cells.


Las células de la granulosa (GC) son componentes esenciales de los folículos y tienen un papel en la regulación del desarrollo de éste. El objetivo del estudio fue investigar ciertos componentes celulares involucrados en la proliferación, diferenciación y características funcionales de las células de la granulosa en el éxito de la fertilización de los ovocitos humanos durante la fertilización in vitro (FIV) a través de técnicas inmunohistoquímicas. En este estudio, se incluyeron 30 pacientes diagnosticados con infertilidad primaria o secundaria, síndrome de ovario poliquístico en el centro de FIV del Departamento de Obstetricia y Ginecología del Hospital Memorial. La cantidad de Hormona Anti Mülleriana (AMH) en la sangre, el diámetro de las células de la granulosa y el diámetro del núcleo celular se midieron en 20 células obtenidas de cada paciente. Además, se evaluó la puntuación de degeneración y las expresiones BAX, ADAMTS-1, IL-10 en células de granulosa (p <0,01). Se estimó que la apoptosis inducida por los GC humanos podría ser un indicador de la calidad del huevo. Se estimó que la expresión moderada de ADAMTS-1 estaba relacionada con el fracaso de la ovulación, el deterioro de la calidad de los ovocitos y la disminución de la tasa de fertilización. La disminución en los niveles de AMH puede estar asociada con defectos en las células de la granulosa. Por lo tanto, el aumento de las células de granulocitos puede explicar la disminución significativa de la secreción de AMH y el aumento de los niveles de expresión de IL10 en personas sanas.


Subject(s)
Humans , Female , Fertilization in Vitro/methods , Interleukin-10/metabolism , bcl-2-Associated X Protein/metabolism , ADAMTS1 Protein/metabolism , Granulosa Cells/metabolism , Immunohistochemistry
10.
Article in Chinese | WPRIM | ID: wpr-847350

ABSTRACT

BACKGROUND: Traditional Chinese medicine has proposed the theory that “treatment for flaccidity aims at Yangming meridian” in the Internal Canon of Medicine. However, relatively few reports focus on electroacupuncture at the Stomach Meridian of Foot-Yangming for the treatment of spinal cord injury. From the perspectives of Bcl-2 and Bcl-2 expression, the mechanism of electroacupuncture intervention at the Stomach Meridian of Foot-Yangming for the treatment of spinal cord injury was preliminarily explored in this study. OBJECTIVE: To investigate the effect of electroacupuncture on the expression of Bax and Bcl-2 in injured segments of spinal cord injury rats. METHODS: Sixty-four Sprague-Dawley female rats (SPF level) were randomly divided into four groups: control group, pre-labeling group, post-injury labeling group and electroacupuncture group, with 16 rats in each group. The control group and the pre-labeling group were given intraperitoneal injection of Brdu (5 mg/kg) for 10 continuous days prior to the operation to label the cells that had differentiation ability and vitality in the spinal cord. The control group underwent laminectomy at T10 segment on the 11th day of labeling, while a model of spinal cord injury was induced by the clamp method in the pre-labeling group. The post-injury labeling group and the electroacupuncture group were injected intraperitoneally with BrdU (5 mg/kg) for 10 continuous days to mark the activated and proliferated cells. In the electroacupuncture group, electroacupuncture stimulation was done at Zusanli and Futu acupoints of Foot-Yangming Stomach Meridian on the 3rd day after modeling, 5 times a week. Four rats were taken from each group at 3, 10, 17, and 24 days after modeling (0, 7, 14, and 21 days after electroacupuncture stimulation). Basso, Beattie and Bresnahan scores were used to evaluate the motor function, and the expressions of Bax and Bcl-2 protein and gene in the spinal cord were detected using qRT-PCR and western blot. RESULTS AND CONCLUSION: At 3-24 days after surgery, the neurological scores in the pre-labeling group, post-injury labeling group, and electroacupuncture group were significantly lower than those in the control group (P < 0.05). The neurological scores of the electroacpuncture group were significantly higher than those in the pre-labeling group and post-injury labeling group (P < 0.05). With the prolongation of spinal cord injury time, the mRNA and protein expressions of Bax increased first and then decreased, while the mRNA and protein expression of Bcl-2 decreased first and then increased. The ratio of Bax/Bcl-2 decreased gradually with the lapse of electroacupuncture intervention time. To conclude, electroacupuncture stimulation of the Stomach Meridian of Foot-Yangming can reduce apoptosis of nerve cells, and promote recovery of motor function in spinal cord injury rats by regulating the expression of Bcl-2 and Bax.

11.
Article in Chinese | WPRIM | ID: wpr-846668

ABSTRACT

Objective: To observe the reversal and prevention effect of New Shengmai Decoction on the rats’ cardiomyocyte apoptosis induced by adriamycin, and provide the experimental foundation basis for the clinical treatment of myocardial injury induced by adriamycin. Method: The rat models with cardiomyocyte apoptosis were established by adriamycin. Forty male SD rats were divided randomly into four groups, including the normal group, the adriamycin model group, the captopril group and the New Shengmai Decoction group. During the experiment, the mental state, activity, feeding, hair color and other conditions of the rats were observed. After 6 weeks of treatment, the cardiac function and left ventricular hypertrophy of rats were measured and the pathological changes of myocardium were observed by HE staining. And the apoptosis of myocardial cells was observed by TUNEL staining and protein expressions of Caspase-3, Bcl-2, and Bax were detected by immunohistochemistry. Results: Compared with the control group, the cardiac function of the model group was significantly decreased. Compared with the model group, the cardiac function of rats after the different drugs’ treatment could be improved in the different degrees and the effect of the New Shengmai Decoction group was significant. Compared with the control group, the heart body ratio, left ventricular hypertrophy index and myocardial cell apoptosis index in the model group were all significantly increased. Compared with the model group, the captopril group and the New Shengmai Decoction group ameliorated cardiac hypertrophy and myocardial cell apoptosis in rats. Compared with the control group, the expression level of bcl-2 protein in the model group was decreased, while the expression level of Bax and Caspase-3 protein was increased. Compared with the model group, captopril and the New Shengmai Decoction increased the expression level of bcl-2 protein and decreased the expression level of Bax and Caspase-3 protein. Conclusion: The New Shengmai Decoction can improve the cardiac function and lessen cardiomyocyte apoptosis of rats. It can also decrease the expression of protein Caspase-3 in the cardiac muscle of rats or inhibit its activity. In order to restrain cardiomyocyte apoptosis, the New Shengmai Decoction can increase the expression of protein Bcl-2 and decrease the expression of protein Bax through improving the expression of Bcl-2/Bax in the cardiac muscle of rats.

12.
Article in Chinese | WPRIM | ID: wpr-846113

ABSTRACT

Objective: To explore the underlying mechanism of Buyang Huanwu Decoction extracts on apoptosis and autophagy in PC12 cells model with oxidative stress injury. Methods: Different level oxidative stress injury models with H2O2 at various concentrations were established. The effective concentrations of Buyang Huanwu Decoction extracts were determined by MTT method in the initial stage and the intensifying period after oxidative stress injury. The apoptosis of PC12 cells were evaluated by FCM and TUNNEL, the autophagy situations were observed by TEM and mRFP-GFP-LC3. Furthermore, the proteins of Bax, Bcl-2, Beclin1, LC3A, and LC3B related to apoptosis were determined by Western blotting. Results: The initial stage and the intensifying period of oxidative stress injury cell models were established by H2O2 at the concentration of 1.5 and 2.0 mmol/L, respectively. Compared with the control group, model group appeared increasing apoptosis and autophagy levels, and model group had higher expressions of Bax/Bcl-2, Beclin1, LC3B and lower expression of LC3A (P < 0.05). Compared with the initial stage of oxidative stress injury cell models, Buyang Huanwu Decoction extracts could reduce the Bax/Bcl-2 and restrain apoptosis rates, while the autophagy was activated by up-regulation Beclin1 and LC3B/LC3A (P < 0.05). When the serious apoptosis and excessive autophagy were observed in the intensifying period of oxidative stress injury cells, the extracts could play the protective effect by apoptosis restraining and autophagy alleviating. Conclusion: Buyang Huanwu Decoction extracts can play the protective effects on oxidative stress injury cell models in different period by regulating apoptosis and autophagy.

13.
Article in Chinese | WPRIM | ID: wpr-793031

ABSTRACT

OBJECTIVE@#To observe the effects of fast-twisting long-retaining (FTLR) acupuncture therapy on apoptosis of vestibular nucleus and expression of Caspase-3, Bcl-2 and Bax in rats with vertigo induced by posterior circulation ischemia.@*METHODS@#A total of 70 healthy SD rats were randomly divided into a sham operation group, a model group, a medication group, a regular acupuncture group and a FTLR acupuncture group, 14 rats in each group. The rats in the model group, medication group, regular acupuncture group and FTLR acupuncture group were intervented with surgical ligation of the right common carotid artery (CCA) and the right subclavian artery (SCA) to establish the model of vertigo induced by posterior circulation ischemia; in the sham operation group, the right CCA and the right SCA were separated without ligation. The rats in the medication group were treated with gavage of flunarizine hydrochloride suspension (10 mL/kg). "Baihui" (GV 20), "Shuaigu" (GB 8) and "Fengchi" (GB 20) were selected in the two acupuncture groups. The rats in the regular acupuncture group were treated with routine acupuncture and the needles were retained for 30 min, while the rats in the FTLR acupuncture group were treated with quick twist (200-300 times/min) for 1 min and the needles were retained for 60 min. The rats in the sham operation group and the model group received no intervention. All the intervention was provided once a day for 10 days. The decline rate of local blood flow in vestibular nucleus was observed; the apoptosis of vestibular nucleus was observed by TUNEL method; the expression of Caspase-3, Bcl-2 and Bax proteins were detected by immunohistochemistry.@*RESULTS@#Compared with the sham operation group, the decline rate of local blood flow in the right vestibular nucleus was significantly increased in the model group (<0.01), and the apoptosis index (AI) of vestibular nucleus was significantly increased (<0.01). Compared with the model group, the decline rates of local blood flow in the right vestibular nucleus in the two acupuncture groups and medication group were significantly reduced (<0.01), and the AIs of vestibular nucleus cells were significantly reduced (<0.01). The decline rate of local blood flow in the right vestibular nucleus in the FTLR acupuncture group was lower than those in the medication group and the regular acupuncture group (<0.01, <0.05), and the AI of vestibular nucleus was lower than those in the regular acupuncture group and the medication group (<0.05). Compared with the sham operation group, the expression of Bcl-2 in the vestibular nucleus was significantly decreased in the model group (<0.01), and the expressions of Bax and Caspase-3 were significantly increased (<0.01). Compared with the model group, the expressions of Bcl-2 in the vestibular nucleus were significantly increased in the two acupuncture groups and medication group (<0.01), and the expressions of Bax and Caspase-3 were significantly reduced (<0.01). The expression of Bcl-2 in the vestibular nucleus in the FTLR acupuncture group was higher than those in the regular acupuncture group and the medication group (<0.05), and the expressions of Bax and Caspase-3 were lower than those in the regular acupuncture group and the medication group (<0.05).@*CONCLUSION@#The FTLR acupuncture therapy could effectively inhibit the apoptosis of vestibular nucleus in rats with vertigo induced by posterior circulation ischemia, and its mechanism may be related to improving the blood supply of vestibular nucleus and regulating the expressions of Caspase-3, Bcl-2 and Bax proteins.

14.
Chinese Pharmacological Bulletin ; (12): 710-715, 2020.
Article in Chinese | WPRIM | ID: wpr-856978

ABSTRACT

Aim To investigate the effect of Xihuang pills on estradiol (E2) and progesterone (P)-induced apoptosis of rat mammary epithelial cells and the expression of estrogen and progesterone receptors, and to explore its anti-mammary hyperplasia mechanism. Methods Rat mammary epithelial cells were treated with different concentrations of Xihuangpills containing serumafter E2, P induced proliferation. The cell proliferation was detected by CCK-8 method (24, 48, 72 h). The apoptosis was detected by flow cytometry after AnnexinV-FITC/PI double staining. The average optical density of Bax and Bcl-2 was detected by immunohistochemistry; Estradiol receptor alpha (ER-α), estradiol receptor beta (ER-β), progesterone receptor (PR) protein expression were detected by Western blot. Results The serum containing Xihuang pillssignificantly inhibitedthe proliferation of rat mammary epithelial cells after E2and P treatment (P < 0. 05), and induced apoptosis, affecting the expression of apoptosis-related proteins Bcl-2 and Bax (P < 0. 05), and effectively inhibiting the expression of estrogen receptors ERα, ERβ. Conclusions Xihuang pills can induce the apoptosis of mammary epithelial cells by regulating related apoptotic proteins, and regulate the secretion of estrogen and progesterone in breast tissues, affecting the proliferation and rejuvenation of breast, which is of great significance for the treatment of breast hyperplasia.

15.
Article in Chinese | WPRIM | ID: wpr-855824

ABSTRACT

AIM: To analyze the apoptosis promoting effect of breviscapine on NSCLC cells and the growth of transplanted tumor and investigate the mechanism. METHODS: The apoptosis, Caspase-3 activity, Bax and Bcl-2 expression of A549 cells treated with 25, 50 and 100 μmol/L breviscapine were detected. The subcutaneous transplanted tumor model was constructed with A549 cells. The mice were intraperitoneally injected with 10 mg/kg and 20 mg/kg breviscapine every day. The size and weight of the tumor were observed every week. On the 21st day, the mice were killed and the tumor was obtained. The expression of Bax and Bcl-2 was detected by Western blot. Bax/Bcl-2 ratio was analyzed. Caspase-3 expression was detected by immunohistochemistry and apoptosis in the tumor was detected by TUNEL staining. RESULTS: Breviscapine increased the apoptosis rate of A549 cells. The results of enzyme labeling showed that Caspase-3 activity increased significantly after breviscapine treatment compared with the control group. Western blot showed that breviscapine could significantly inhibit the expression of anti-apoptosis protein Bcl-2, increase the expression of pro-apoptosis protein Bax, and increase the ratio of Bax/Bcl-2. In vivo, on the 14th and 21st day, the tumor size of the treatment group was significantly smaller than that of the control group, while the weight of nude mice was not significantly reduced. Western blot showed that breviscapine could upregulate the expression of Bax and down regulate the expression of Bcl-2 in the transplanted tumor, while the expression of Caspase-3 was significantly increased. TUNEL staining showed that the proportion of apoptosis increased significantly compared with the control after breviscapine treatment. CONCLUSION: Breviscapine can induce the apoptosis of A549 cells in vitro and in vivo. The mechanism may be that breviscapine upregulates Bax expression and downregulates Bcl-2 expression, increases Bax/Bcl-2 ratio, activates Caspase-3, resulting in A549 cell apoptosis.

16.
Acta Pharmaceutica Sinica B ; (6): 1397-1413, 2020.
Article in English | WPRIM | ID: wpr-828800

ABSTRACT

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC GSDME-dependent pyroptosis.

17.
Article in Chinese | WPRIM | ID: wpr-821714

ABSTRACT

Objective @#To investigate the effect and mechanism of allicin combined with 5-FU on proliferation inhibition and apoptosis of the mucoepidermoid carcinoma MEC-1 cell line in mucoepidermoid carcinoma in order to provide the corresponding basis for subsequent clinical drug application.@*Methods @# MEC-1 cells in the logarithmic growth phase were randomly divided into control groups and experimental groups. The control groups were PBS groups containing 0.1% DMSO, while the experimental groups were the allicin group, 5-FU group and combined drug group (the allicin combined with the 5-FU group). The proliferation inhibition rates of allicin, 5-FU and allicin combined with 5-FU in MEC-1 cells were detected by the CCK8 method at different concentrations (0, 25, 50, and 75 mg/L) for 24 h, and the IC50 value of allicin and 5-FU after 24 hours was calculated. The apoptotic rate of MEC-1 cells treated with allicin, 5-FU and allicin combined with 5-FU at different concentrations (0, 25, 50, and 75 mg/L) for 24 hours was measured by flow cytometry. The expression of Bax and Bcl-2 protein was determined by Western blot analysis of the IC50 concentration of allicin and 5-FU alone and in combination with MEC-1 cells for 24 hours. @*Results@#The growth inhibition rate and apoptosis rate of MEC-1 cells in the combined drug group were higher than those in the allicin group and the 5-FU alone group (P < 0.01). Allicin and 5-FU alone and in combination downregulated Bcl-2 protein and upregulated Bax protein expression, and the combined drug group had the largest ratio of Bax/Bcl-2 (P < 0.05). @*Conclusion @#Allicin and 5-FU both alone and in combination can inhibit the proliferation of and induce apoptosis in MEC-1 cells, and allicin can enhance the apoptosis of 5-FU in MEC-1 cells, which may be related to the apoptosis of the mitochondrial pathway.

18.
Braz. j. med. biol. res ; 53(5): e9108, 2020. tab, graf
Article in English | LILACS | ID: biblio-1098110

ABSTRACT

Recent evidence suggests that aerobic physical training may attenuate the deleterious effects of cancer risk factors, including smoking. We investigated the effects of cigarette smoke inhalation and aerobic physical training on the expression of steroid receptors and inflammatory and apoptotic proteins in the prostate. Forty male Wistar rats were distributed in four groups: control (CO), exercise (EXE), cigarette smoke exposure (CS), and cigarette smoke exposure with exercise (CS+EXE). For eight weeks, animals were repeatedly exposed to cigarette smoke for 30 min or performed aerobic physical training either with or without the cigarette smoke inhalation protocol. Following these experiments, we analyzed prostate epithelial morphology and prostatic expression of androgen (AR) and glucocorticoid receptors (GR), insulin-like growth factor (IGF-1), B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) via immunohistochemistry. Cigarette smoke exposure stimulated the expression of AR, IGF-1, BCL-2, and NF-κB while downregulating BAX, IL-6, and TNF-α labeling in the prostate. In contrast, aerobic physical training attenuated cigarette smoke-induced changes in AR, GR, IGF-1, BCL-2, IL-6, TNF-α, and NF-κB. This suggests that cigarette smoke stimulates inflammation and reduces apoptosis, culminating in increased prostatic epithelial and extracellular matrices, whereas physical training promoted beneficial effects towards maintaining normal prostate morphology and protein levels.


Subject(s)
Animals , Male , Rats , Physical Conditioning, Animal , Prostate/pathology , Smoke/adverse effects , Biomarkers/analysis , Prostate/drug effects , Time Factors , Immunohistochemistry , Rats, Wistar , Disease Models, Animal , Inflammation
19.
J. appl. oral sci ; 28: e20200124, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1134800

ABSTRACT

Abstract Objectives To evaluate apoptotic levels of peripheral blood mononuclear cells (PBMCs) and apoptotic regulatory proteins (Bax and Bcl-2) in lymphocyte subsets of oral cancer (OC) patients and healthy controls (HC). Methodology The percentage of apoptotic cells and lymphocyte counts were measured in the first cohort using PBMCs obtained from 23 OC patients and 6 HC. In the second cohort, (OC, 33; HC, 13), the mean fluorescence intensity (MFI) of Bax and Bcl-2 in CD19+ B, CD4+ T, CD8+ T, and CD16+56+ natural killer (NK) cells was determined via flow cytometry. Results The percentage of apoptotic cells was higher in the PBMCs of OC patients than in HC patients, particularly in patients with stage IV cancer (p<0.05). However, lymphocyte counts were significantly lower in stage IV patients (p<0.05). NK CD19+ B and CD16+56+ cell counts were significantly lower in OC patients compared with HC patients (p<0.001 and p<0.01, respectively), but CD4+ T cells were interestingly significantly higher in OC patients (p<0.001). While Bax MFI was slightly higher, Bcl-2 MFI was significantly lower for all four lymphocyte subsets in OC samples, particularly in stage IV patients, when compared with HC. Consequently, Bax/Bcl-2 ratios showed an upward trend from HC to OC patients, particularly those in stage IV. We found similar trends in Bax and Bcl-2 MFI for tumor stage, tumor size, and lymph node involvement. Conclusions The increased lymphocyte apoptosis in stage IV OC patients may be related to higher Bax levels and lower Bcl-2 levels. The Bax/Bcl-2 ratio in lymphocytes may be useful to determine the prognosis of OC patients, and could be considered a mean for supportive treatment in the future.


Subject(s)
Humans , Mouth Neoplasms , Leukocytes, Mononuclear , Killer Cells, Natural , Lymphocyte Subsets , Apoptosis , Flow Cytometry
20.
Braz. J. Pharm. Sci. (Online) ; 56: e18861, 2020. tab, graf
Article in English | LILACS | ID: biblio-1249162

ABSTRACT

Adverse changes occur gradually in the skeletal muscles with age via continuous exposure to oxidative stress. Quercetin, a member of the flavonoids family, possesses anti-oxidative and radical-scavenging activities. Therefore, this study investigated the role of quercetin to modulate age-induced changes in the transcript levels of some apoptosis-related genes in rat's gastrocnemius muscles, up to 15 months-old. Half of the rats at each age (1, 5, 10 and 15 months old) were given a vehicle and the other half was given 200 mg/kg quercetin for 2 weeks, respectively. With the increase of age, vehicle groups showed hyalinization of the muscle fibers and a decrease of the catalase and an increase of the malondialdehyde levels. Down-regulation of Bcl2 gene and up-regulation of both NF-κB and Bax genes were recorded. Interestingly, quercetin groups showed focal hyalinization of the muscle fibers at both 10th and 15th months old. An increase in the catalase and a decrease in malondialdehyde levels, up-regulation of Bcl2 gene and down-regulation of both NF-κB and Bax genes were recorded. In conclusion, quercetin minimized age-induced alteration in the morphological structure and the expression of the apoptosis-related genes via increasing the antioxidant defense in the gastrocnemius muscle.


Subject(s)
Animals , Male , Rats , Role , Apoptosis , Muscle, Skeletal , Muscles , Quercetin/analysis , Flavonoids/analysis , Down-Regulation , Up-Regulation , Oxidative Stress , Antioxidants/adverse effects
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