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1.
Eur J Clin Pharmacol ; 80(3): 383-393, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151504

RESUMO

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is essential for the post-marketing safety evaluation of drugs. Therefore, good monitoring of ADRs is vital for strengthening drug supervision, management, and guiding rational drug use. Chinese medical institutions are the primary source of ADR case reports, but the proportion of the reports in grade IIIA hospitals is still low due to serious under-reporting. The 3rd Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People's Hospital, also has such a problem. OBJECTIVE: To improve the quantity and quality of ADR reports and enhance the level of pharmacovigilance in hospitals, the Third Affiliated Hospital of Chengdu Medical College, People's Hospital of Chengdu Pidu District experienced 10 years to gradually establish a management model to improve the medical staff's reporting rate of spontaneous reporting of ADRs. The management model is led by clinical pharmacists and combines the PDCA with Teach-back methods. The purpose of this paper is to introduce the management model and discuss its advantages and shortcomings of this model. METHODS: This study was conducted at the Third Affiliated Hospital of Chengdu Medical College-Chengdu Pidu District People's Hospital. From 2016, the daily management of reporting, auditing, and data improvement of adverse drug reactions in the hospital was carried out by clinical pharmacists, who used the PDCA method combined with the Teach-back method to continuously improve the reporting program of ADRs in the hospital during 2016-2021. Then, the proportion of spontaneous reports of total, new, and serious ADRs was compared before and after the intervention. Also, we performed a time series analysis using an autoregressive moving average model to assess changes in the total number of spontaneous ADR reports before the intervention (2013-2015), the first intervention (2016-2018), and the second intervention (2019-2021). RESULTS: After the combined PDCA and Teach-back method intervention, the median number of reported ADRs per year increased from 50 (range 37-55) in the pre-intervention period to 88 (range 83-162) in the first intervention period and to 374 in the second (range 312-566). Breakpoint regression analysis of the spontaneous reporting rate of ADRs showed that the instantaneous increase after the first intervention was not statistically significant (P = 0.526). However, the reporting rate of ADRs increased at a month-by-month growth rate during the second intervention compared to the first intervention. Its spontaneous reporting rate improved 1.034 times (P = 0.002). After the second intervention, the spontaneous reporting rate of ADRs transiently increased 6.111-fold (P < 0.001), and the month-to-month growth rate increased 1.024-fold (P < 0.001) again. CONCLUSION: The management model that combines the PDCA and the Teach-back method significantly improves the reporting rate of adverse drug reactions.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Fatores de Tempo , Hospitais , Farmacovigilância , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , China
2.
BMC Pregnancy Childbirth ; 24(1): 251, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589784

RESUMO

BACKGROUND: Inflammatory Bowel Disease (IBD) affects reproductive-aged women. Active disease can lead to decreased fertility. Although the vast majority of international guidelines recommend for the continuation of anti-TNF-α during pregnancy, recent studies have raised concerns about the safety of anti-tumor necrosis factor-α (TNF-α) therapy during pregnancy, both for patients and for physicians. METHODS: Studies that evaluate the safety of anti-TNF-α therapy in pregnant women with IBD were identified using bibliographical searches. An updated meta-analysis was performed for pregnancy outcomes, such as live birth, abortion, still birth, preterm birth, low birth weight, congenital abnormalities, and neonatal infection. Odds ratio (OR) with 95% confidence interval (CI) are reported. Data on disease activity, timing of anti-TNF-α therapy were collected for further analysis. RESULTS: Overall, 11 studies were screened from on-line databases and international meeting abstracts. An increased risk of abortion (OR, 1.33; 95% CI, 1.02-1.74; P = 0.04) and preterm birth (OR, 1.16; 95% CI, 1.05-1.28; P = 0.004), and a decreased risk of live birth (OR, 0.83; 95% CI, 0.74-0.94; P = 0.002]) were found in the anti-TNF-α therapy group compared with the control group (no use of anti-TNF-α therapy). The subgroup analyses based on the disease activity showed there is no significant association between the use of anti-TNF-α therapy during pregnancy on adverse pregnancy outcomes of abortion, preterm birth, and live birth. The rates of still birth, low birth weight, and congenital abnormalities in the anti-TNF-α therapy group were not significantly different from those in the control group. CONCLUSIONS: Anti-TNF-α therapy does not increase the risks of still birth, low birth weight, and congenital abnormalities; however it may be assicated with increased risks of abortion and preterm birth, which are accompanied by a lower rate of live birth. Although these findings may be confounding by potential disease activity, they offer some opposite viewpoints with biologic agent use. Therefore, more studies are required to further confirm the safety of anti-TNF-α therapy in pregnancy with IBD.


Assuntos
Doenças Inflamatórias Intestinais , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Adulto , Nascimento Prematuro/epidemiologia , Inibidores do Fator de Necrose Tumoral , Resultado da Gravidez/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Natimorto , Necrose , Complicações na Gravidez/tratamento farmacológico
3.
Molecules ; 29(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38338359

RESUMO

In this study, two previously undescribed nitrogen-containing compounds, penisimplicins A (1) and B (2), were isolated from Penicillium simplicissimum JXCC5. The structures of 1 and 2 were elucidated on the basis of comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS data. The absolute configuration of 2 was determined by Marfey's method, ECD calculation, and DP4+ analysis. Both structures of 1 and 2 feature an unprecedented manner of amino acid-derivatives attaching to a polyketide moiety by C-C bond. The postulated biosynthetic pathways for 1 and 2 were discussed. Additionally, compound 1 exhibited significant acetylcholinesterase inhibitory activity, with IC50 values of 6.35 µM.


Assuntos
Alcaloides , Penicillium , Policetídeos , Estrutura Molecular , Policetídeos/química , Acetilcolinesterase/metabolismo , Penicillium/química , Peptídeos/metabolismo , Alcaloides/química
4.
Arch Biochem Biophys ; 743: 109672, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37336341

RESUMO

Autophagy is a highly conserved biological process that has evolved across evolution. It can be activated by various external stimuli including oxidative stress, amino acid starvation, infection, and hypoxia. Autophagy is the primary mechanism for preserving cellular homeostasis and is implicated in the regulation of metabolism, cell differentiation, tolerance to starvation conditions, and resistance to aging. As a multifunctional protein, DJ-1 is commonly expressed in vivo and is associated with a variety of biological processes. Its most widely studied role is its function as an oxidative stress sensor that inhibits the production of excessive reactive oxygen species (ROS) in the mitochondria and subsequently the cellular damage caused by oxidative stress. In recent years, many studies have identified DJ-1 as another important factor regulating autophagy; it regulates autophagy in various ways, most commonly by regulating the oxidative stress response. In particular, DJ-1-regulated autophagy is involved in cancer progression and plays a key role in alleviating neurodegenerative diseases(NDS) and defective reperfusion diseases. It could serve as a potential target for the regulation of autophagy and participate in disease treatment as a meaningful modality. Therefore, exploring DJ-1-regulated autophagy could provide new avenues for future disease treatment.


Assuntos
Neoplasias , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Hipóxia/metabolismo , Autofagia/fisiologia , Proteína Desglicase DJ-1/metabolismo
5.
J Nat Prod ; 86(7): 1736-1745, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37436927

RESUMO

In our ongoing study of fungal bioactive natural products, 12 previously undescribed triquinane sesquiterpene glycosides, namely, antrodizonatins A-L (1-12), and four known compounds (13-16) have been obtained from the fermentation of the basidiomycete Antrodiella zonata. The structures were established unambiguously via extensive spectroscopic analysis and theoretical calculations of electronic circular dichroism spectra. This is the first report of triquinane sesquiterpene glycosides. Compounds 1, 5, and 12 displayed antibacterial activity against Staphylococcus aureus with MIC50 values of 35, 34, and 69 µM, respectively.


Assuntos
Basidiomycota , Polyporales , Sesquiterpenos , Glicosídeos/farmacologia , Glicosídeos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Basidiomycota/química , Estrutura Molecular
6.
Sensors (Basel) ; 23(20)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37896709

RESUMO

Timely and accurate flame detection is a very important and practical technology for preventing the occurrence of fire accidents effectively. However, the current methods of flame detection are still faced with many challenges in video surveillance scenarios due to issues such as varying flame shapes, imbalanced samples, and interference from flame-like objects. In this work, a real-time flame detection method based on deformable object detection and time sequence analysis is proposed to address these issues. Firstly, based on the existing single-stage object detection network YOLOv5s, the network structure is improved by introducing deformable convolution to enhance the feature extraction ability for irregularly shaped flames. Secondly, the loss function is improved by using Focal Loss as the classification loss function to solve the problems of the imbalance of positive (flames) and negative (background) samples, as well as the imbalance of easy and hard samples, and by using EIOU Loss as the regression loss function to solve the problems of a slow convergence speed and inaccurate regression position in network training. Finally, a time sequence analysis strategy is adopted to comprehensively analyze the flame detection results of the current frame and historical frames in the surveillance video, alleviating false alarms caused by flame shape changes, flame occlusion, and flame-like interference. The experimental results indicate that the average precision (AP) and the F-Measure index of flame detection using the proposed method reach 93.0% and 89.6%, respectively, both of which are superior to the compared methods, and the detection speed is 24-26 FPS, meeting the real-time requirements of video flame detection.

7.
Molecules ; 28(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36985677

RESUMO

The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.


Assuntos
Marsdenia , Plantas Medicinais , Humanos , Plantas Medicinais/química , Marsdenia/química , China , Pregnanos/química , Glicosídeos/química
8.
Biochem Biophys Res Commun ; 637: 276-285, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36410277

RESUMO

Myocardial Ischemic Injury is a serious threat to human health, and DJ-1 is involved in cardioprotection. The research intended to explore the effects and mechanism of DJ-1 to protect myocardium against ischemia injury. DJ-1 overexpression lentivirus vectors were transduced into the myocardium of SD rats and H9c2 cells, and an AMI model in vivo and a hypoxia model in vitro were established, respectively. Results showed that DJ-1 overexpression alleviated myocardial ischemia injury, as demonstrated by reduced the extent of myocardial infarction, improved cell survival, decreased LDH activity and CK-MB release. Furthermore, DJ-1 interacted with RACK1, activated AMPK/mTOR pathway, induced adaptive autophagy and protected the myocardium. However, RACK1 siRNA or compound C (an AMPK inhibitor) could weaken the above effect of DJ-1 on myocardium. In conclusion, DJ-1 could activate adaptive autophagy by the RACK1/AMPK/mTOR pathway and protect the myocardium against ischemia injury.


Assuntos
Proteínas Quinases Ativadas por AMP , Traumatismos Cardíacos , Proteína Desglicase DJ-1 , Animais , Humanos , Ratos , Autofagia , Hipóxia , Isquemia , Miocárdio , Proteínas de Neoplasias , Ratos Sprague-Dawley , Receptores de Quinase C Ativada , Serina-Treonina Quinases TOR , Proteína Desglicase DJ-1/metabolismo
9.
Mol Biol Rep ; 48(8): 6075-6083, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34374892

RESUMO

BACKGROUND: Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. METHODS AND RESULTS: DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling key proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. CONCLUSIONS: Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.


Assuntos
Neoplasias do Endométrio/metabolismo , NF-kappa B/metabolismo , Proteína Desglicase DJ-1/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Neoplasias do Endométrio/genética , Endopeptidases/metabolismo , Endopeptidases/fisiologia , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteína Desglicase DJ-1/genética , Transdução de Sinais/genética
10.
Dig Dis Sci ; 66(8): 2651-2660, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32914380

RESUMO

BACKGROUND: Oxaliplatin is one of the most effective chemotherapeutic drugs used for the treatment of colorectal cancer (CRC). However, intervention that attenuates the resistance of oxaliplatin is still required in the treatment of CRC. AIMS: To investigate the role of miR-325 in changing the oxaliplatin sensitivity to CRC cells. METHODS: Expression of miR-325 in colorectal cancer tissues and cell lines was measured by using qRT-PCR analysis. Cytotoxicity of oxaliplatin to control or miR-325-overexpressed HT29 and SW480 cells was evaluated by CCK-8 assays. Luciferase reporter assay was used to confirm the regulation of miR-325 on HSPA12B. Flow cytometry was performed to detect the mitochondrial membrane potential and cell apoptosis. RESULTS: Expression of miR-325 was decreased in colorectal cancer tissues and cell lines. However, overexpression of miR-325 can decrease the 50% inhibiting concentration of oxaliplatin to colorectal cancer cell lines HT29 and SW480. Mechanically, we confirmed that miR-325 targeted HSPA12B in colorectal cancer. Therefore, overexpression of miR-325 inhibited the phosphorylation of PI3K and AKT and decreased the expression of Bcl-2 to promote the oxaliplatin-induced mitochondrial apoptosis in colorectal cancer. CONCLUSIONS: MiR-325 sensitizes the colorectal cancer cells to oxaliplatin-induced cytotoxicity through the HSPA12B/PI3K/AKT/Bcl-2 pathway.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , MicroRNAs/metabolismo , Oxaliplatina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Antineoplásicos/farmacologia , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Humanos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
11.
J Cardiovasc Pharmacol ; 75(4): 305-313, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32040033

RESUMO

Resveratrol (Res) was recently reported to ameliorate hypoxia/reoxygenation (H/R)-caused oxidative stress in H9c2 cardiomyocytes through promoting the mitochondrial translocation of DJ-1 protein and subsequently preserving the activity of mitochondrial complex I. However, it is noteworthy that DJ-1 possesses no mitochondria-targeting sequence. Therefore, how Res induces DJ-1 mitochondrial translocation is an important and interesting question for further exploration. Glucose-regulated protein 75 (Grp75), whose N-terminus contains a 51-amino acid long mitochondrial-targeting signal peptide, is a cytoprotective chaperone that partakes in mitochondrial import of several proteins. Here, the contribution of Grp75 to mitochondrial import of DJ-1 by Res was investigated in a cellular model of H/R. Our results showed that Res upregulated the expression of DJ-1 protein, enhanced the interaction of DJ-1 and Grp75, and promoted DJ-1 translocation to mitochondria from cytosol in H9c2 cardiomyocytes undergoing H/R. Importantly, knockdown of Grp75 markedly reduced the interaction of DJ-1 with Grp75 and subsequent DJ-1 mitochondrial translocation induced by Res. Furthermore, Res pretreatment promoted the association of DJ-1 with ND1 and NDUFA4 subunits of complex I, preserved the activity of complex I, decreased mitochondria-derived reactive oxygen species production, and eventually ameliorated H/R-caused oxidative stress damage. Intriguingly, these effects were largely prevented also by small interfering RNA targeting Grp75. Overall, these results suggested that Grp75 interacts with DJ-1 to facilitate its translocation from cytosol to mitochondria, which is required for Res-mediated preservation of mitochondria complex I and cardioprotection from H/R-caused oxidative stress injury.


Assuntos
Antioxidantes/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteína Desglicase DJ-1/metabolismo , Resveratrol/farmacologia , Animais , Hipóxia Celular , Linhagem Celular , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Proteínas de Choque Térmico HSP70/genética , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Proteínas Mitocondriais/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , NADH Desidrogenase/metabolismo , Transporte Proteico , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos
12.
Org Biomol Chem ; 18(13): 2410-2415, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32195526

RESUMO

Xylarilongipins A (1) and B (2), two diterpenes each with an unusual cage-like bicyclo[2.2.2]octane moiety, along with their biosynthetic precursor hymatoxin L (3), were isolated from the culture broth of the fungicolous fungus Xylaria longipes HFG1018 inhabiting in the medicinal fungus Fomitopsis betulinus. The structures and absolute configurations of the three compounds were established by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Xylarilongipin A (1) displayed moderate inhibitory activity against the cell proliferation of concanavalin A-induced T lymphocytes and lipopolysaccharide-induced B lymphocytes with IC50 values of 13.6 and 22.4 µM, respectively. Additionally, the biosynthetic pathways for compounds 1-3 are discussed. This work not only corroborates the structure of the 9,16-cyclo-(18-nor-)isopimarane skeleton by single-crystal X-ray diffraction analysis for the first time, but also provides new insights into the biosynthetic origin of the unusual diterpene skeletons.


Assuntos
Compostos Bicíclicos com Pontes/farmacologia , Diterpenos/farmacologia , Imunossupressores/farmacologia , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/toxicidade , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/toxicidade , Humanos , Imunossupressores/química , Imunossupressores/toxicidade , Xylariales/química
13.
J Nat Prod ; 83(2): 401-412, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31961677

RESUMO

Eighteen new nor-isopimarane diterpenes, xylarinorditerpenes A-R (1-18), along with two previously reported compounds, 14α,16-epoxy-18-norisopimar-7-en-4α-ol (19) and the labdane-type diterpene agatadiol (20), were isolated from cultures of the fungicolous fungus Xylaria longipes HFG1018 isolated from the wood-rotting basidiomycete Fomitopsis betulinus. The structure elucidation and relative configuration assignments of 1-18 were accomplished by interpretation of spectroscopic data and through computational methods. The absolute configurations of 1, 4, and 16 were determined by single-crystal X-ray diffraction. Compounds 1-16 possess an 18- or 19-nor-isopimarane skeleton, and compounds 17 and 18 possess an 18,19-dinor-isopimarane skeleton. Compounds 2-5, 9, 14, 19, and 20 showed immunosuppressive activity but were devoid of cytotoxicity against the cell proliferation by concanavalin A-induced T lymphocytes and lipopolysaccharide-induced B lymphocytes, with IC50 values varying from 1.0 to 27.2 µM and from 16.1 to 51.8 µM, respectively.


Assuntos
Abietanos/química , Ascomicetos/química , Diterpenos/química , Imunossupressores/química , Xylariales/química , Basidiomycota , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/farmacologia , Imunossupressores/farmacologia , Estrutura Molecular , Polyporales/química
14.
Acta Biochim Biophys Sin (Shanghai) ; 52(11): 1202-1214, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079995

RESUMO

Gastric cancer is a common malignancy worldwide. The occurrence of multidrug resistance (MDR) is the major obstacle for effective gastric cancer chemotherapy. In this study, the in-depth molecular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated. The results showed that DJ-1 expression level was higher in MDR variant SGC7901/VCR cells than that in its parental SGC7901 cells. Moreover, DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells, while DJ-1 knockdown in SGC7901/VCR cells induced re-sensitization to adriamycin, vincristine, cisplatin, and 5-fluorouracil. These results suggested that DJ-1 mediated the development of MDR in SGC7901 gastric cancer cells. Importantly, further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells. Meanwhile, we found that PI3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN, consequently resulting in Nrf2 phosphorylation and activation, and thereby inducing Nrf2-dependent P-glycoprotein (P-gp) and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells. Overall, these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells. The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells, prompting its further investigation as a molecular target to overcome MDR.


Assuntos
Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Desglicase DJ-1/genética , Proteína Desglicase DJ-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Cromonas/farmacologia , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Fluoruracila/farmacologia , Técnicas de Silenciamento de Genes , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Morfolinas/farmacologia , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/ultraestrutura , Regulação para Cima , Vincristina/farmacologia
15.
Biochem Biophys Res Commun ; 514(2): 401-406, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31053297

RESUMO

Resveratrol, a multi-functional phytoalexin, has been well indicated to exert cardioprotective effects by weakening ischemia/reperfusion (I/R) injury, and cell apoptosis is a vital way in I/R injury. SIRT1-p53 pathway has strong significance in regulating cell apoptosis. DJ-1 can directly bind to SIRT1 and stimulate the activity of SIRT1-p53. Therefore, the current study was determined whether Resveratrol attenuates hypoxia/reoxygenation (H/R)-induced cell apoptosis, and whether DJ-1-mediated SIRT1 activation involves in the cardioprotective effects of Resveratrol. The results showed that remarkable decrease in the number of apoptotic cells along with reduction of lactate dehydrogenase release and restoration of cell viability emerged when Resveratrol was applied in the H9c2 cells exposed to H/R. Moreover, Resveratrol increased DJ-1 expression and promoted the interaction of DJ-1 with SIRT1, which further contributed to subsequent restoration of SIRT1 activity and decrease of acetylation level of p53. However, above cardioprotective effects of Resveratrol were abrogated by DJ-1 siRNA and SIRT1 specific inhibitor Sirtinol. In conclusion, the current study demonstrated that Resveratrol suppressed H/R-induced cell apoptosis, which may be conducted by up-regulating DJ-1, and later activating SIRT1 activity and subsequently inhibiting p53 acetylation level in the H9c2 cells.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Hipóxia Celular , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Proteína Desglicase DJ-1/metabolismo , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Animais , Linhagem Celular , Sobrevivência Celular , Ativação Enzimática , L-Lactato Desidrogenase/metabolismo , Ligação Proteica , Proteína Desglicase DJ-1/biossíntese , Ratos , Proteína Supressora de Tumor p53/química
16.
Biochem Biophys Res Commun ; 519(1): 73-80, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31477270

RESUMO

Gastric cancer (GC) is one of the most malignant tumors with high incidence and mortality worldwide, and the multidrug resistance (MDR) often results in chemotherapy failure in GC. DJ-1 has been well indicated to be associated with drug resistance in multiple cancers. However, the role of DJ-1 in the MDR of gastric cancer cells and its possible mechanism remain to be elucidated. Therefore, the current study was investigated whether DJ-1 expression is differential in parental gastric cancer cell SGC7901 and vincristine (VCR)-induced gastric cancer MDR cell SGC7901/VCR, and whether DJ-1 plays a significant role in development of MDR in gastric cancer. The results showed that DJ-1 expression in SGC7901/VCR cells was significantly higher than its sensitive parental SGC7901 cells. Furthermore, DJ-1 overexpressed gastric cancer cell line SGC7901/LV-DJ-1 led to the increase of cell survival rate, the IC50 of chemotherapeutic drugs and number of cell clones as well as decrease of cell cycle G0/G1 phase ratio compared with its parental cells under the treatment of VCR, adriamycin (ADR), 5-Fluorouracil (5-FU) and cisplatin (DDP). However, the DJ-1 knockdown stable cell line SGC7901/VCR/shDJ-1 reversed the above mentioned series of MDR. Moreover, it was found that upregulation of DJ-1 protein expression promoted the pumping rate of GC cells to ADR and reduced the apoptotic index of GC cells treated with chemotherapeutic drugs by upregulating P-gp and Bcl-2. Similarly, knocking down DJ-1, P-gp or Bcl-2 displayed a converse effect. In conclusion, the current study demonstrated that DJ-1 overexpression confers the MDR phenotype to SGC7901 cells and this process is related to DJ-1 promoting active efflux of drugs and enhancing the anti-apoptotic ability of MDR GC cells by upregulating P-gp and Bcl-2.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Desglicase DJ-1/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima/efeitos dos fármacos , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Fenótipo , Proteína Desglicase DJ-1/antagonistas & inibidores , Proteína Desglicase DJ-1/metabolismo , Células Tumorais Cultivadas
17.
J Org Chem ; 84(4): 1845-1852, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30673259

RESUMO

Irpexolidal (1), a triterpenoid with an unprecedented carbon skeleton, along with its biogenetic-related compound irpexolide A (2), were isolated from the fruiting bodies of the medicinal fungus Irpex lacteus. Irpexolidal features a 6/5/6/5/6/5-fused polycyclic skeletal system which arises from the eburicane-type triterpene by a 6,7- seco-6,8- cyclo pattern. The structures of 1 and 2 were established by means of extensive spectroscopic techniques, ECD calculation, and DP4+ probability based on GIAO NMR chemical shift calculations. The plausible biosynthetic pathways for compounds 1 and 2 were proposed. Their biological activities were evaluated.


Assuntos
Carbono/química , Carpóforos/química , Triterpenos/química , Vias Biossintéticas , Espectroscopia de Ressonância Magnética
18.
J Nat Prod ; 82(1): 45-50, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30629435

RESUMO

Two new Tricholoma terpenoids, tricholopardins A and B, were isolated from the fruiting bodies of the basidiomycetes Tricholoma pardinum. Their structures were elucidated by spectroscopic methods, as well as electronic circular dichroism and optical rotatory dispersion calculations. Tricholopardin A potently inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with an IC50 of 0.08 µM. Its anti-inflammatory effects on three inflammatory mediators were also evaluated. A plausible biosynthetic pathway for these products is discussed.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Carpóforos/metabolismo , Terpenos/isolamento & purificação , Tricholoma/metabolismo , Animais , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7 , Células THP-1 , Terpenos/química , Terpenos/farmacologia
19.
Chem Biodivers ; 16(9): e1900364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381262

RESUMO

Two new C13 -polyketides, aureonitols A and B (1 and 2), along with five known compounds (3-7), were isolated from the solid fermentation culture of the plant endophytic fungus Chaetomium globosum from the aerial parts of Salvia miltiorrhiza. The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic data analysis and computed methods. Compound 5 was found to display the remarkable antimicrobial activities against four multidrug-resistant bacteria (Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Staphylococcus epidermidis) with MIC values of 3.13-6.25 µg/mL (ciprofloxacin: 0.78-1.56 µg/mL), and also against all tested fungal strains with MIC values of 3.13-25 µg/mL (ketoconazole: 0.78-12.50 µg/mL).


Assuntos
Antibacterianos/farmacologia , Chaetomium/química , Furanos/farmacologia , Policetídeos/farmacologia , Salvia miltiorrhiza/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Chaetomium/metabolismo , Relação Dose-Resposta a Droga , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Fermentação , Furanos/química , Furanos/isolamento & purificação , Testes de Sensibilidade Microbiana , Conformação Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
20.
J Asian Nat Prod Res ; 21(7): 603-609, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29665722

RESUMO

Three new vibralactone derivatives, namely vibralactones U-W (1-3), together with vibralactone (4), have been isolated from cultures of the basidiomycete Boreostereum vibrans. Their structures were determined on the basis of spectroscopic methods and literature data. All compounds showed no activities to five human cancer cell lines.


Assuntos
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Basidiomycota/química , Lactonas/química , Lactonas/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
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