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1.
Acta Pharmaceutica Sinica B ; (6): 33-49, 2022.
Article in English | WPRIM | ID: wpr-929280

ABSTRACT

Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ that governs body energy metabolism. Autophagy's role in hepatic energy regulation has just begun to emerge and autophagy seems to have a much broader impact than what has been appreciated in the field. Though classically known for selective or bulk degradation of cellular components or energy-dense macromolecules, emerging evidence indicates autophagy selectively regulates various signaling proteins to directly impact the expression levels of metabolic enzymes or their upstream regulators. Hence, we review three specific mechanisms by which autophagy can regulate metabolism: A) nutrient regeneration, B) quality control of organelles, and C) signaling protein regulation. The plasticity of the autophagic function is unraveling a new therapeutic approach. Thus, we will also discuss the potential translation of promising preclinical data on autophagy modulation into therapeutic strategies that can be used in the clinic to treat common metabolic disorders.

2.
J. appl. oral sci ; 30: e20210413, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360532

ABSTRACT

Abstract The mechanisms that stimulate the proliferation of epithelial cells in inflammatory periapical lesions are not completely understood and the literature suggests that changes in the balance between apoptosis and immunity regulation appear to influence this process. Objective: To evaluate the expression of the epidermal growth factor (EGF), its receptor (EGFR) and of the keratinocyte growth factor (KGF), the presence of CD57+ cells, the epithelial cell proliferation index, and the expression of the Bcl-2 protein in inflammatory periapical lesions (IPL) at different stages of development. Methodology: Our sample was composed of 52 IPLs (22 periapical granulomas - PG - and 30 periapical cysts - PC), divided into three groups: PGs, small PCs, and large PCs. Specimens were processed for histopathologic and immunohistochemical analyses. Sections were evaluated according to the amount of positive staining for each antibody. Results: We found no significant differences among the groups regarding Bcl-2 (p=0.328) and Ki-67 (p>0.05) expression or the presence of CD57+ cells (p=0.748). EGF (p=0.0001) and KGF (p=0.0001) expression was more frequent in PCs than in PGs, and CD57+ cells were more frequent in IPLs with intense inflammatory infiltrates (p=0.0001). We found no significant differences in KGF (p=0.423), Bcl-2 (p=0.943), and EGF (p=0.53) expression in relation to inflammatory infiltrates or to the type of PC epithelial lining, but observed greater KGF expression (p=0.0001) in initial PCs. EGFR expression was similar among the groups (p>0.05). Conclusion: More frequent EGF and KGF expression in PCs and the greater presence of CD57+ cells in lesions with intense inflammatory infiltrates suggest that these factors influence IPL development. The greater KGF expression in initial PCs suggests its importance for the initial stages of PC formation.

3.
China Pharmacy ; (12): 1082-1087, 2022.
Article in Chinese | WPRIM | ID: wpr-923756

ABSTRACT

OBJECTIVE To study the regulator y mech anism of glaucocalyxin A (GLA) on autophagy and apoptosis of HCCLM3 hepatocellular carcinoma cells. METHODS HCCLM3 cells were taken ,and control group ,GLA 2.5 μg/mL group,GLA 5 μg/mL group and GLA 10 μg/mL group were mainly set according to different experimental purposes. In control group,only complete medium was added ;in each administration group ,complete medium containing the corresponding final concentration of GLA was added. Cell cycle distribution and apoptosis were detected by flow cytometry ;mitochondrial morphology and autophagy were observed by transmission electron microscope (only control group ,GLA 5 μg/mL group);JC-1 staining and fluorescence inverted microscope were used to observe and detect the mitochondrial membrane potential of the cells ;Western blot assay was used to detect the protein expression of Bcl- 2, Bax, Beclin1 and cleaved caspase- 3 proteins in the cells ; the co-immunoprecipitation method was used to detect the binding and dissociation of Bcl- 2 and Beclin 1(only GLA 5 μg/mL group, GLA 10 μg/mL group). RESULTS Compared with control group ,GLA 5 μg/mL and GLA 10 μg/mL could induce a significant arrest of the cell cycle in the G 2-M phase for HCCLM 3,a significant decrease in mitochondrial membrane potential ,an increase in apoptosis as well as significant promotion of the protein expression of Bax ,cleaved caspase- 3 and Beclin 1,and significant inhibition of the protein expression of Bcl- 2(P<0.01). GLA 5 μg/mL also significantly changed mitochondrial morphology and increased autophagosomes. The results of co-immunoprecipitation showed that compared with GLA 5 μg/mL,GLA 10 μg/mL could enhance the binding of Bcl- 2 and Beclin 1. CONCLUSIONS GLA can regulate the autophagy and apoptosis of HCCLM 3 cells by Bcl-2/Beclin1 target. The effect is closely related to the dose of GLA.

4.
Braz. j. biol ; 81(4): 1133-1143, Oct.-Dec. 2021. graf
Article in English | LILACS | ID: biblio-1153449

ABSTRACT

Abstract Apoptosis is a sequential order of cell death occurring regularly to ensure a homeostatic balance between the rate of cell formation and cell death. However, a misplaced of this balancing function can contribute to an abnormal cell growth / proliferation or autoimmune disorders etc. Apoptosis is therefore said to be crucial from the point of development of an embryo throughout the growth of an organism contributing to the renewal of tissues and also the getting rid of inflammatory cells. This review seeks to elaborate on the recent overview of the mechanism involved in apoptosis, some element and signal contributing to its function and inhibition together with how their malfunction contribute to a number of cancer related cases.


Resumo A apoptose é uma ordem sequencial de morte celular que ocorre regularmente para garantir um equilíbrio homeostático entre a taxa de formação e a morte celular. No entanto, um desequilíbrio dessa função pode contribuir para um crescimento/proliferação celular anormal ou distúrbios autoimunes. A apoptose é, portanto, considerada crucial do ponto de desenvolvimento de um embrião ao longo do crescimento de um organismo que contribui para a renovação dos tecidos e também a eliminação de células inflamatórias. Esta revisão procura elaborar a recente visão geral do mecanismo envolvido na apoptose, alguns elementos e sinais que contribuem para sua função e inibição, além de como o mau funcionamento deles contribui para vários casos relacionados ao câncer.


Subject(s)
Apoptosis
5.
Article in Chinese | WPRIM | ID: wpr-912851

ABSTRACT

Objective: To explore whether acupuncture can improve sleep disturbance, cognitive impairment and emotional disorders caused by sleep deprivation, and its association with the attenuation of oxidative stress injury in prefrontal cortex. Methods: Fifty-two male Sprague-Dawley rats were randomly divided into a control group (n=10), a model group (n=14), a manual acupuncture (MA) group (n=14), and a sham-MA group (n=14). All the groups were established as sleep deprivation models via the modified multiple platform method, except for the control group. Rats in both the MA group and the sham-MA group received corresponding intervention, respectively. After modeling and intervention, the four groups received three behavioral tests, namely sleep monitoring, by comprehensive lab animal monitoring system (CLAMS), Morris water maze (MWM) test and open-field test (OFT), followed by oxygen free radical level test and Western blot (WB) detection for the expression levels of Bax and Bcl-2. Results: The MA group derived more sleep time within 24 h than either the model group or the sham-MA group (both P<0.05). On MWM orientation navigation test day 1, there were no significant differences in escape latency among the control, MA and sham-MA groups (P>0.05), and the escape latency was significantly shorter in these three groups than that in the model group (all P<0.05). On test day 4, the escape latency was markedly shorter in the MA group than that in either the model group or the sham-MA group (both P<0.05); meanwhile, the MA group showed significantly better performance compared with these two groups in space probe test (both P<0.05). In OFT, compared with the control group, there was a significant decline in the horizontal movement score in the other three groups (all P<0.05), and the decrease was more significant in the model group and the sham-MA group than that in the MA group (both P<0.05). The superoxide dismutase (SOD) content was markedly higher and the malondialdehyde (MDA) content was markedly lower in the MA group than those in the model group and the sham-MA group (all P<0.05). Compared with the model group and the sham-MA group, the expression of Bax was significantly lower and the expression of Bcl-2 was significantly higher in the MA group (all P<0.05). Conclusion: MA therapy can lengthen the sleep time in sleep-deprived rats and improve learning and memory impairments induced by sleep deprivation, and the underlying mechanism may be associated with the enhancement of antioxidant capacity in the prefrontal cortex and the inhibition of hippocampal neuronal apoptosis.

6.
Article in Chinese | WPRIM | ID: wpr-910781

ABSTRACT

Objective:To explore the potential value of interim 18F-fluorodeoxyglucose (FDG) PET/CT combined with B-cell lymphoma-2 (Bcl-2)/MYC protein dual expression (DE) status in the prognostic stratification for patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). Methods:Forty-six patients (21 males, 25 females; age 20-83 years) with newly diagnosed PGI-DLBCL from June 2012 to May 2019 in Nanjing Drum Tower Hospital were enrolled in this retrospective study. Immunohistochemistry for Bcl-2 and MYC protein expression was performed. All patients underwent baseline and interim (after 2-4 cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP) regimen) 18F-FDG PET/CT scans for assessment. Interim 18F-FDG PET/CT results were determined based on Deauville 5-point scale (DS) and changing rate of maximum standardized uptake value (ΔSUV max%) in 18F-FDG PET/CT images. Kaplan-Meier survival analysis, Cox proportional hazards regression model (single factor, multiple factors analysis) were used to analyze the prognosis (3-year progression free survival (PFS) and overall survival (OS) rates). Results:Patients were followed up for 6-84 months, and 14 showed disease progression and 9 died. The PFS rate and OS rate were 69.6% and 80.4%, respectively. DE, DS as well as ΔSUV max% were significant predictors of PFS (hazard ratio ( HR) values: 3.280, 5.120, 9.167, all P<0.05); lactate dehydrogenase (LDH), MYC protein expression, DS and ΔSUV max% were significant predictors of OS ( HR values: 4.091, 9.618, 7.697, 11.151, all P<0.05). Multivariate analysis revealed that DS and ΔSUV max% were independent predictors of PFS and OS ( HR values: 4.370-9.244, all P<0.05). In the DS negative (-) group, patients with DE positive (+ ) had lower PFS and OS rates than those with DE- (PFS rate: 50.0% vs 88.9%; OS rate: 66.7% vs 96.3%; χ2 values: 6.050, 4.966, both P<0.05). In ΔSUV max%<90% group, patients with DE+ had lower PFS rate than those with DE- (12.5% vs 68.8%; χ2=6.649, P=0.01). Conclusions:Interim PET/CT analysis using DS and ΔSUV max% is able to predict survival in PGI-DLBCL patients. The combination of DS, ΔSUV max% and DE can risk-stratify PGI-DLBCL patient more effectively.

7.
Article in Chinese | WPRIM | ID: wpr-907833

ABSTRACT

Objective:To explore the characteristics of multimodal ultrasound before neoadjuvant chemotherapy (NAC) and the degree of postoperative pathological remission and B-cell lymphoma-2 (BCL-2) .Methods:From Jan. 2018 to Dec. 2020, female breast cancer patients who underwent breast-conserving or total mastectomy surgery at Shaanxi Hospital of traditional Chinese Medicine were selected as the research objects. Routine ultrasound, automatic breast full-volume imaging, and contrast-enhanced ultrasound were performed before chemotherapy. The postoperative pathological remission was evaluated according to Miller and Payne’s modified pathological response grading standard. The expression of BCL-2 in breast cancer tissue was detected by immunohistochemistry. Univariate analysis was performed on the characteristics of MHR, NMHR and bcl-2 with different expression status. Then, binary Logistic regression was used to analyze the significant variables in univariate analysis.Results:Among 186 patients, 84 patients (45.2%) were in MHR group and 102 patients (54.8%) in NMHR group after NAC surgery. The maximum diameter of mass in NMRH group was > 4 cm. The proportion of CM, irregular shape of mass, microcalcification, high enhancement of CEUS and perfusion defect (62.7%, 62.7%, 70.6%, 62.7%, 66.7%) was significantly higher than that of MRH group (38.1%, 40.5%, 39.3%, 41.7%, 31.0%, P<0.05) . The proportion of irregular shape, microcalcification, Alder blood flow grade 2-3, hyperenhancement and peripheral radiation enhancement in low bcl-2 expression patients (65.1%, 69.8%, 65.1%, 71.7%, 72.6%, respectively) was significantly higher than that in high Bcl-2 expression patients (36.2%, 38.7%, 27.5%, 28.7%, 38.8% respectively) (all P<0.05) . Multivariate Logistic analysis showed that irregular masses, with microcalcifications, and high CEUS performance were independent risk factors for NMHR (all P<0.05) ; irregular masses, with microcalcifications, and CEUS manifestations of peripheral radial enhancement were independent risk factors for low expression of BCL-2 (all P<0.05) . Conclusion:Multimodal ultrasound features can be used to predict the degree of pathological remission and the expression of BCL-2 in breast cancer patients with NAC, which helps to select treatment options and predict the prognosis of patients.

8.
Journal of Leukemia & Lymphoma ; (12): 407-410, 2021.
Article in Chinese | WPRIM | ID: wpr-907192

ABSTRACT

Objective:To investigate the expressions and significance of cyclin D2 and bcl-2 in diffuse large B-cell lymphoma (DLBCL) and their clinical significances.Methods:The tissues of 87 DLBCL patients undergoing resection and 23 patients with lymphoid tissue reactive hyperplasia (RLH) in the First Central Hospital of Baoding from January 2015 to March 2020 were collected. Immunohistochemistry method was used to detect the expressions of cyclin D2 and bcl-2 in tissues of DLBCL and RLH, and the relationship between the expressions of cyclin D2 and bcl-2 as well as the association with the clinicopathological features of DLBCL patients.Results:The positive rates of cyclin D2 protein in DLBCL and RLH were 33.3% (29/87) and 2.0% (1/23), the positive rates of bcl-2 protein in DLBCL and RLH were 60.9% (54/87) and 7.0% (3/23); the positive rates of cyclin D2 and bcl-2 in DLBCL were higher than those in RLH, and the differences were statistically significant( χ2=7.566, P=0.006; χ2=17.512, P < 0.01). The expressions of cyclin D2 and bcl-2 proteins were related to the Ann Arbor staging and immunophenotype of DLBCL patients (all P < 0.05), while not related to age, gender, cancer location, tissue type (all P > 0.05). There was a positive correlation between the expressions of cyclin D2 and bcl-2 protein in DLBCL ( r=1.000, P < 0.01). Conclusions:cyclin D2 and bcl-2 may be related to the development and progression of DLBCL, and both may have some synergies.

9.
Article in Chinese | WPRIM | ID: wpr-906516

ABSTRACT

Objective:To investigate the effect of Weiwei Tongtiao decoction on gastric mucosal pathology and the expression level of inhibitor kappa B kinase <italic>β</italic>(IKK<italic>β</italic>) and B-cell lymphoma-2(Bcl-2)in rats with chronic atrophic gastritis (CAG) precancerous lesion. Method:SD rats were randomly divided into normal group, model group, positive drug Weifuchun group, Weiwei Tongtiao decoction high, medium and low dose treatment groups. The rat model of CAG precancerous lesion was prepared by <italic>N</italic>-methyl-<italic>N</italic>'-nitro-<italic>N</italic>-nitrosoguanidine (MNNG)compound modeling method. weiwei Tongtiao decoction high, medium and low dose treatment groups received intragastric administration of 24, 12, 6 g·kg<sup>-1</sup> Weiwei Tongtiao decoction respectively, while Weifuchun group received 0.45 g·kg<sup>-1</sup> Weifuchun suspension, once per day for 12 weeks. The pathological changes of gastric mucosa of rats were observed by hematoxylin-eosin(HE)staining, and the mRNA and protein levels of IKK<italic>β</italic> and Bcl-2 in gastric mucosa of rats were detected by Real-time quantitative polymerase chain reaction (Real-time PCR), immunohistochemistry(IHC)and Western blot. Result:Compared with the normal group, 100% inherent gland atrophy, mild to severe intestinal metaplasia, and 25% low-grade intraepithelial neoplasia were observed under microscope in model group. All Weifuchun group and Weiwei Tongtiao decoction groups could improve the atrophy of gastric glands, moderate to severe intestinal metaplasia and pathological injury of low-grade intraepithelial neoplasia, especially at high dose group. Compared with the normal group, IKK<italic>β</italic>, Bcl-2 mRNA and protein expressions in the gastric mucosa of the model group were up-regulated (<italic>P</italic><0.01). Compared with the model group, the mRNA and protein expressions of IKK<italic>β</italic> and Bcl-2 in gastric mucosa of rats in the Weifuchun group and the Weiwei Tongtiao decoction high, medium and low dose groups were down-regulated (<italic>P</italic><0.05,<italic>P</italic><0.01), showing a dose-dependent relationship, and such levels in the Weiwei Tongtiao decoction high-dose intervention group were similar to those in normal group. Conclusion:Weiwei Tongtiao decoction can improve and even reverse gastric mucosa with CAG precancerous lesions in rats, and its intervention mechanism may be related to down-regulating the expressions of IKK<italic>β</italic> and Bcl-2 in gastric mucosa.

10.
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.

11.
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.

12.
Article in Chinese | WPRIM | ID: wpr-905825

ABSTRACT

Objective:To observe the effect of Danggui Niantongtang on the protein and mRNA expression of key regulatory factors of the extrinsic and intrinsic apoptotic pathway in synovial tissue of adjuvant arthritis (AA) rats, and to further explore the mechanism of Danggui Niantongtang in the prevention and treatment of rheumatoid arthritis. Method:The general condition of AA rats, including its body weight, were observed. The changes of toe volume were detected by toe volume meter. Histopathological changes of synovium of knee joint were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expression levels of tumor necrosis factor receptor super family 6 (Fas), Fas-associating protein with a novel death domain(FADD), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase Caspase-3 (Caspase-3) were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. Result:Compared with the normal group, the toe volume of the model group increased significantly (<italic>P</italic><0.01), with significantly proliferated synovial cells, significantly reduced mRNA and protein expression levels of Fas, FADD, Bax and Caspase-3 in synovial tissues(<italic>P</italic><0.05,<italic> P</italic><0.01), and significantly increased Bcl-2 level (<italic>P</italic><0.01). Compared with the model group, the swelling degree of toes in Danggui Niantongtang group and Tripterygium group was significantly alleviated (<italic>P</italic><0.01), with significantly improved synovial hyperplasia, significantly increased mRNA and protein expression levels of Fas, FADD, Bax and Caspase-3 (<italic>P</italic><0.05, <italic>P</italic><0.01), and significantly decreased expression levels of bcl-2 mRNA and protein (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:Danggui Niantongtang can effectively reduce joint swelling and abnormal proliferation of synovial tissue in AA rats. Its mechanism may be related to regulating the expression of Fas, FADD, Bax, Bcl-2 and Caspase-3, and promoting the apoptosis of synovial cells.

13.
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.

14.
Acta Pharmaceutica Sinica ; (12): 1911-1920, 2021.
Article in Chinese | WPRIM | ID: wpr-887002

ABSTRACT

This research explored the synergistic effects and the potential mechanisms of RCE-4 and various nonsteroidal anti-inflammatory drugs (NSAIDs) on the proliferation of cervical cancer Ca Ski cells. The MTT assay and CalcuSyn V2.0 software were used to detect cell proliferation and calculate the combination index (CI); the expression levels of various proteins were analyzed using Western blot assay; mitochondrial membrane potential (MMP) was assessed using JC-1 staining; acridine orange/ethidium bromide (AO/EB) double-fluorescence staining was used to detect the apoptosis of Ca Ski cells; a co-immunoprecipitation (Co-IP) assay was used to analyze the relative content of Bcl-2-Beclin 1 complex in Ca Ski cells. The results demonstrate that the combination of RCE-4 and NSAIDs increases the inhibition of Ca Ski cells compared to the single-RCE-4 group, and celecoxib provided the best synergistic effect among the four NSAIDs tested, with a CI of 0.32. The combination of RCE-4 and celecoxib significantly down-regulated the expression of cyclooxygenase-2 (COX-2) and nuclear transcription factor-κB (NF-κB), and promoted the expression of non-steroidal anti-inflammatory drugs activity gene-1 (NAG-1). In addition, autophagy induced by RCE-4 was markedly inhibited in combination with celecoxib, which was associated with down-regulation of the expression of microtubule-associated protein 3 (LC3)-II, Beclin 1, p62 and autophagy-related gene (ATG) 3/4B/5/7/14. RCE-4-induced apoptosis was significantly enhanced by altering the depolarization of mitochondrial membrane potential and the expression of B cell lymphoma-2 (Bcl-2), B cell lymphoma-xl (Bcl-xl), Bcl-2 associated X protein (Bax), Bcl-2/Bcl-xl-associated death promoter (Bad) and cleaved cysteinyl aspartate specific proteinase (cleaved-caspase) 3/7/9. Furthermore, the formation of the Bcl-2-Beclin 1 complex was significantly inhibited in Ca Ski cells treated with RCE-4 in combination with celecoxib. Taken together, this research shows that the combination of RCE-4 and celecoxib has a significant synergistic effect on the proliferation of Ca Ski cells by promoting apoptosis, inhibiting autophagy and disturbing the formation of the Bcl-2-Beclin 1 complex, which may be a novel strategy to increase the sensitivity of anti-cervical cancer drugs.

15.
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.

16.
Article in Chinese | WPRIM | ID: wpr-882193

ABSTRACT

@#[摘 要] 目的:探讨miR-125a-5p通过调控Bcl-2相关永生基因4(Bcl-2-associated athanogene 4,BAG4)的表达抑制胃癌细胞迁移和侵袭的分子机制。方法:选用2014年1月至2015年12月兰州大学第一医院手术切除的82例胃癌组织标本及配对的癌旁组织以及人胃癌细胞系MGC803、BGC823、SGC7901、HGC27及人胃黏膜上皮细胞(GES-1),qPCR法检测胃癌组织、癌旁组织及胃癌细胞系中miR-125a-5p的表达水平。分别将miR-125a-5p mimic、miR-125a-5p inhibitor、(si-BAG4)siRNA-BAG4及阴性对照质粒转染至胃癌细胞,划痕愈合实验和Transwell侵袭实验分别检测miR-125a-5p/BAG4信号轴对胃癌细胞迁移和侵袭能力的影响。WB检测胃癌细胞中BAG4蛋白的表达。荧光素酶报告基因实验验证miR-125a-5p和BAG4之间的靶向调控关系。结果:miR-125a-5p在胃癌组织和细胞系中均低表达(均P<0.01)。miR-125a-5p的表达与患者的性别(P=0.953)、年龄(P=0.772)、肿瘤部位(P=0.867)、组织学分级(P=0.745)和肿瘤大小(P=0.088)无相关性,与胃癌患者的T分期(P=0.003)、N分期(P=0.001)、M分期(P=0.027)和TNM分期(P=0.035)显著相关,差异有统计学意义。miR-125a-5p低表达是胃癌患者总生存时间的独立危险因素。过表达miR-125a-5p显著抑制胃癌细胞的迁移和侵袭能力(均P<0.01)。敲降BAG4可逆转miR-125a-5p inhibitor对胃癌细胞迁移和侵袭能力的抑制作用。荧光素酶报告基因实验证实miR-125a-5p可与BAG4 3'非翻译区(untranslated regions,UTR)结合抑制其表达。结论:miR-125a-5p通过靶向下调BAG4的表达水平进而抑制胃癌细胞的迁移和侵袭。

17.
Acta Pharmaceutica Sinica B ; (6): 1148-1157, 2021.
Article in English | WPRIM | ID: wpr-881190

ABSTRACT

As one of the most lethal diseases, pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities. Furthermore, pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found. Although combinations of new drugs, multimodal therapies, and adjuvants prolong survival, most patients still relapse after surgery and eventually die. Consequently, the search for more effective treatments for pancreatic cancer is highly relevant and justified. As a newly re-discovered mediator of gasotransmission, hydrogen sulfide (H

18.
Acta Pharmaceutica Sinica B ; (6): 609-620, 2021.
Article in English | WPRIM | ID: wpr-881159

ABSTRACT

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-

19.
Acta Pharmaceutica Sinica B ; (6): 322-339, 2021.
Article in English | WPRIM | ID: wpr-881139

ABSTRACT

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in

20.
Acta Pharmaceutica Sinica B ; (6): 309-321, 2021.
Article in English | WPRIM | ID: wpr-881138

ABSTRACT

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination and degradation, and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes. Phosphorylation, either of substrates or receptors of CRLs, can alter their interaction. Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases, most often tumorigenesis. These processes have the potential to be used for tumor intervention through the regulation of the activities of related kinases, along with the regulation of the stability of specific oncoproteins and tumor suppressors. This review describes the mechanisms and biological functions of crosstalk between phosphorylation and ubiquitination, and most importantly its influence on tumorigenesis, to provide new directions and strategies for tumor therapy.

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