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1.
Chin J Integr Med ; 30(5): 387-397, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38302647

RESUMO

OBJECTIVE: To develop an interference-free and rapid method to elucidate Guanxin II (GX II)'s representative vasodilator absorbed bioactive compounds (ABCs) among enormous phytochemicals. METHODS: The contents of ferulic acid, tanshinol, and hydroxysafflor yellow A (FTA) in GX II/rat serum after the oral administration of GX II (30 g/kg) were detected using ultra-performance liquid chromatography-mass spectrometry. Totally 18 rats were randomly assigned to the control group (0.9% normal saline), GX II (30 g/kg) and FTA (5, 28 and 77 mg/kg) by random number table method. Diastolic coronary flow velocity-time integral (VTI), i.e., coronary flow or coronary flow-mediated dilation (CFMD), and endothelium-intact vascular tension of isolated aortic rings were measured. After 12 h of exposure to blank medium or 0.5 mmol/L H2O2, endothelial cells (ECs) were treated with post-dose GX II of supernatant from deproteinized serum (PGSDS, 300 µL PGSDS per 1 mL of culture medium) or FTA (237, 1539, and 1510 mg/mL) for 10 min as control, H2O2, PGSDS and FTA groups. Nitric oxide (NO), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA) and phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated endothelial nitric oxide synthase (p-eNOS) were analyzed. PGSDS was developed as a GX II proxy of ex vivo herbal crude extracts. RESULTS: PGSDS effectively eliminates false responses caused by crude GX II preparations. When doses equaled the contents in GX II/its post-dose serum, FTA accounted for 98.17% of GX II -added CFMD and 92.99% of PGSDS-reduced vascular tension. In ECs, FTA/PGSDS was found to have significant antioxidant (lower MDA and higher SOD, P<0.01) and endothelial function-protective (lower VEGF, ET-1, P<0.01) effects. The increases in aortic relaxation, endothelial NO levels and phosphorylated PI3K/Akt/eNOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester (L-NA, eNOS inhibitor) and wortmannin (PI3K/AKT inhibitor), respectively, indicating an endothelium-dependent vasodilation via the PI3K/AKT-eNOS pathway (P<0.01). CONCLUSION: This study provides a strategy for rapidly and precisely elucidating GX II's representative in/ex vivo cardioprotective absorbed bioactive compounds (ABCs)-FTA, suggesting its potential in advancing precision ethnomedicine.


Assuntos
Endotélio Vascular , Vasodilatação , Animais , Vasodilatação/efeitos dos fármacos , Masculino , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Ratos Sprague-Dawley , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Óxido Nítrico/metabolismo , Vasodilatadores/farmacologia , Vasodilatadores/farmacocinética , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/farmacocinética , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo
2.
Histopathology ; 61(5): 974-83, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22804228

RESUMO

AIMS: Proliferation of plasmacytoid dendritic cells (PDCs) occurs in both reactive lymphoid hyperplasia and myeloproliferative disorders, especially chronic myelomonocytic leukaemia. PDCs in the former appear reactive, but in the latter are reported to be clonally related to the underlying myeloid neoplasm. Langerhans cells (LCs), another type of dendritic cell, also proliferate in both reactive dermatoses and, rarely, myeloproliferative disorders, such as acute leukaemia. METHODS AND RESULTS: We report a rare case of tumorous proliferation of PDCs and LCs in the systemic lymph nodes in a 55-year-old man with acute myeloid leukaemia. A microsatellite instability assay showed identical patterns of short tandem repeats in both microdissected PDC and LC components, along with blood blasts. CONCLUSIONS: We hypothesize that the combined proliferations of PDCs and LCs derive from the same haematopoietic stem cells, but that they differentiate divergently under the effect of different microenvironments.


Assuntos
Células Dendríticas/patologia , Células de Langerhans/patologia , Leucemia Mieloide Aguda/patologia , Antígenos CD/metabolismo , Crise Blástica/genética , Crise Blástica/metabolismo , Crise Blástica/patologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Proliferação de Células , Células Dendríticas/metabolismo , Humanos , Imuno-Histoquímica , Células de Langerhans/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Linfonodos/patologia , Masculino , Instabilidade de Microssatélites , Repetições de Microssatélites , Pessoa de Meia-Idade
3.
J Cutan Pathol ; 39(2): 274-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22211369

RESUMO

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.


Assuntos
Infecções por HIV , HIV-1 , Infecções por Herpesviridae , Herpesvirus Humano 8 , Linfoma de Células B , Linfoma Anaplásico de Células Grandes , Neoplasias Cutâneas , Adulto , Biomarcadores Tumorais/biossíntese , Diagnóstico Diferencial , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Infecções por HIV/virologia , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Humanos , Linfoma de Células B/complicações , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma de Células B/virologia , Linfoma Anaplásico de Células Grandes/complicações , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/virologia , Masculino , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia
4.
Cell Death Dis ; 13(11): 917, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319631

RESUMO

Thioredoxin reductase 1 (TXNRD1) is one of the major redox regulators in mammalian cells, which has been reported to be involved in tumorigenesis. However, its roles and regulatory mechanism underlying the progression of HCC remains poorly understood. In this study, we demonstrated that TXNRD1 was significantly upregulated in HCC tumor tissues and correlated with poor survival in HCC patients. Functional studies indicated TXNRD1 knockdown substantially suppressed HCC cell proliferation and metastasis both in vitro and in vivo, and its overexpression showed opposite effects. Mechanistically, TXNRD1 attenuated the interaction between Trx1 and PTEN which resulting in acceleration of PTEN degradation, thereby activated Akt/mTOR signaling and its target genes which conferred to elevated HCC cell mobility and metastasis. Moreover, USF2 was identified as a transcriptional suppressor of TXNRD1, which directly interacted with two E-box sites in TXNRD1 promoter. USF2 functioned as tumor suppressor through the downstream repression of TXNRD1. Further clinical data revealed negative co-expression correlations between USF2 and TXNRD1. In conclusion, our findings reveal that USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Humanos , Carcinoma Hepatocelular/patologia , Tiorredoxina Redutase 1/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Hepáticas/patologia , Regulação para Cima , Proliferação de Células , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Mamíferos , Fatores Estimuladores Upstream/genética
5.
J Cell Biochem ; 112(3): 881-93, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21328461

RESUMO

The endoplasmic reticulum (ER) is essential for lipid biosynthesis, and stress signals in this organelle are thought to alter lipid metabolism. Elucidating the mechanisms that underlie the dysregulation of lipid metabolism in hepatocytes may lead to novel therapeutic approaches for the treatment of lipid accumulation. We first tested the effects of several inhibitors on lipid dysregulation induced by tunicamycin, an ER stress inducer. Triacsin C, an inhibitor of long-chain acyl-CoA synthetase (ACSL) 1, 3, and 4, was the most potent among these inhibitors. We then analyzed the expression of the ACSL family during ER stress. The expression of ACSL3 was induced by ER stress in HuH-7 cells and in mice livers. ACSL3 shRNA, but not ACSL1 shRNA, inhibited the induction of lipid accumulation. GSK-3ß inhibitors attenuated ACSL3 expression and the lipid accumulation induced by ER stress in HuH-7 cells. shRNA that target GSK-3ß also inhibited the upregulation of ACSL3 and lipid accumulation in HuH-7 and HepG2 cells. The hepatitis B virus mutant large surface protein, which is known to induce ER stress, increased the lipid content of cells. Similarly, Triacsin C, and GSK-3ß inhibitors abrogated the lipid dysregulation caused by the hepatitis B virus mutant large surface protein. Altogether, ACSL3 and GSK-3ß represent novel therapeutic targets for lipid dysregulation by ER stress.


Assuntos
Coenzima A Ligases/metabolismo , Retículo Endoplasmático/fisiologia , Quinase 3 da Glicogênio Sintase/metabolismo , Hepatócitos/metabolismo , Lipídeos/biossíntese , Fígado/metabolismo , Animais , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Inibidores Enzimáticos/farmacologia , Glicogênio Sintase Quinase 3 beta , Proteínas de Choque Térmico/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Interferência de RNA , Estresse Fisiológico , Triazenos/farmacologia , Tunicamicina/farmacologia , Regulação para Cima
6.
Front Behav Neurosci ; 15: 783056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35058758

RESUMO

Oxidative stress is closely related to the occurrence of depression. Acupuncture has been proved to be an effective method for treating depression. In order to explore the mechanism of the antidepressant effect of acupuncture, this study performed acupuncture prevention on chronic unpredictable mild stress (CUMS) depression model rats, and observed the effect of acupuncture on hippocampal oxidative stress and Nrf2 signaling pathway. Male SD rats were randomly divided into control group, CUMS group, acupuncture group, and fluoxetine group (n = 10/group). Fluoxetine, a common antidepressant, was used as a positive control drug in this study. In the fluoxetine group, rats were given fluoxetine (2.1 mg/kg) intragastrically once a day for 28 days. The acupoints of Shangxing (GV23) and Fengfu (GV16) were applied in acupuncture group, once every other day for 14 times in total. Behavioral tests and biological detections were used to evaluate the effects of the interventions and the changes of factors related to oxidative stress, Nrf2 pathway, and neuronal apoptosis. The results showed that both acupuncture and fluoxetine could increase sugar preference rate in SPT and decrease immobility time in FST in depression model rats. It also significantly decreased oxidative stress products such as ROS and H2O2, and elevated the protein and mRNA expressions of Nrf2 and HO-1. From Nissl's staining, there were more abundant nerve cells in two intervention groups compared with CUMS group. Plus, acupuncture down-regulated the expression levels of Bax and caspase-3 and up-regulated the expression of Bcl-2. Our findings indicate that acupuncture improved depression-like behaviors of CUMS rats. And CUMS-induced depression-like behaviors in rats were related to oxidative stress and neuronal apoptosis in hippocampus. Acupuncture showed antidepressant effects in reducing oxidative stress products via regulating the Nrf2/HO-1 signaling pathway so that prevented neuronal apoptosis.

7.
Curr Med Sci ; 41(1): 46-50, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582904

RESUMO

Positive nucleic acid (NA) results have been found in recovered and discharged COVID-19 patients, but the proportion is unclear. This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results, and the relationship between the specific antibody production and positive NA rate. According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan. 28 and Mar. 6, 2020 were collected. A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included. Days of viral shedding and specific antibodies were recorded and assessed. Among NA tests in respiratory samples (throat swabs, nasopharyngeal swabs, sputum and flushing fluid in alveoli), the patients with all-negative NA results accounted for 17.20%, those with single-positive results for 46.63%, and those with multiple-positive results for 36.17% respectively. Besides, the recurrent positive NA results after consecutively negative results appeared in 66 patients (11.70%). For multiple-positive patients, median viral shedding duration was 20 days (range: 1 to 57 days). Of the 205 patients who received 2 or more antibody tests, 141 (68.78%) had decreased IgG and IgM concentrations. IgM decreased to normal range in 24 patients, with a median of 44 days from symptom onset. Viral shedding duration was not significantly correlated with gender, age, disease severity, changes in pulmonary imaging, and antibody concentration. It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests. In order to reduce the recurrent positive proportion after discharge, 3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.


Assuntos
Anticorpos Antivirais/análise , COVID-19/diagnóstico , SARS-CoV-2/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/imunologia , Feminino , Guias como Assunto , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Masculino , Pessoa de Meia-Idade , Sistema Respiratório/virologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , Eliminação de Partículas Virais
8.
J Gastroenterol Hepatol ; 23(8 Pt 1): 1169-74, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18505413

RESUMO

The discovery of "ground glass" hepatocytes (GGH) that contain hepatitis B virus (HBV) surface antigens by Hadziyannis and Popper in 1973 represents a historical landmark in the pathology of chronic HBV infection. Different types of GGH have been correlated to the expression patterns of surface/core antigens and the stages of virus replication. The original two types (designated types I & II) of GGH were found to contain specific pre-S mutants with deletions over either pre-S1 or pre-S2 regions, respectively. Type II GGH consistently harbor pre-S2 deletion mutants, which can escape from immune attack and grow preferentially to form clusters. Both types of pre-S mutants can induce endoplasmic reticulum (ER) stress and oxidative DNA damage. The pre-S2 mutants, albeit inducing a weaker level of ER stress signals, could additionally initiate ER stress-independent retinoblastoma/adenovirus E2 promoter binding factor/cyclin A signaling through their interaction with c-Jun activation domain binding protein 1 to degrade p27, illustrating the growth advantage of type II GGH. The combined effects of genomic instability and the proliferation of hepatocytes harboring pre-S mutants could potentially lead to hepatocarcinogenesis over the decades of chronic HBV infection. The presence of pre-S mutants in sera was reported to carry a high risk of developing hepatocellular carcinoma (HCC). Furthermore, transgenic mice harboring pre-S2 mutant plasmids have been shown to develop a dysplastic change of hepatocytes and HCC. Therefore, in addition to being a histological marker of chronic HBV infection, GGH, particularly type II GGH, may represent the preneoplastic lesions of HBV-related HCC.


Assuntos
Hepatite B Crônica/genética , Hepatócitos/patologia , Neoplasias Hepáticas/genética , Precursores de Proteínas/genética , Proteína S/genética , Animais , Hepatite B Crônica/patologia , Hepatócitos/virologia , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Mutação , Precursores de Proteínas/biossíntese , Proteína S/biossíntese
9.
Chin J Integr Med ; 24(10): 785-788, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30267370

RESUMO

It has been well known that insomnia and sleep deprivation can lead to many metabolic diseases such as type 2 diabete mellitus (T2DM). Chinese medicine (CM) has been used to improve insomnia and showed many good therapeutic effects. Some Coptidis Rhizoma-contained traditional formulae have been found to exert obvious effects on insomnia, such as Jiaotai Pill (), Huanglian Ejiao Decoction (), Huanglian Wendan Decoction (), Niuhuang Qingxin Pill (), and Zhusha Anshen Pill (). Coptidis Rhizoma, a traditional herbal medicine which can purge Xin (Heart) fire, is the most important component of these formulas. Studies have found that these formulae could improve T2DM symptoms. We hypothesized that treating insomnia theoretically may help to prevent diabetes and organized many experimental studies in this review and concluded that Coptidis Rhizoma-contained traditional formulae for insomnia might be a potential to prevent diabetes.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Coptis chinensis , Medicamentos de Ervas Chinesas/farmacologia , Disbiose/complicações , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos
10.
Curr Med Sci ; 38(4): 704-713, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30128882

RESUMO

This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD). OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 (Cryl) and cryptochrome 2 (Cry2) in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B (NF-κB) p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3', 5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP) in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.


Assuntos
Criptocromos/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Hipotálamo/efeitos dos fármacos , Privação do Sono/tratamento farmacológico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Criptocromos/genética , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Glucose/metabolismo , Hipotálamo/metabolismo , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Regulação para Cima
11.
Chin J Integr Med ; 23(12): 901-907, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28986813

RESUMO

OBJECTIVE: To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD). METHODS: Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined. RESULTS: The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. CONCLUSIONS: JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Intestinos/patologia , Privação do Sono/tratamento farmacológico , Animais , Proteínas CLOCK/metabolismo , Relógios Circadianos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Íleo/efeitos dos fármacos , Íleo/patologia , Lipopolissacarídeos , Masculino , Modelos Biológicos , Ocludina/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Ratos Sprague-Dawley
12.
Aquat Toxicol ; 80(4): 338-45, 2006 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-17098300

RESUMO

Some free fatty acids are toxic to phytoplankton, and the toxic effects are multiple. However, precisely how they kill phytoplankton is debatable. Here we show that fatty acids result in damage to plasma membranes, which might account for their lethal effects on phytoplankton. In this study, we used two chlorophytes (Chlorella vulgaris Beij. and Monoraphidium contortum (Thur.) Kom.-Legn.) and a cyanobacterium (Anabaena P-9) as test organisms. When these organisms were treated with deleterious concentrations of fatty acids, a remarkable elevation of extracellular potassium (K+) was detected in the culture medium; this indicates that leakage of intracellular K+ occurred as a result of damage to the plasma membranes. Exposure to unsaturated fatty acids resulted in higher levels of leaked K+ than did exposure to saturated ones, and levels of leakage displayed a positive correlation with the susceptibility of the growth of organisms to fatty acids. Stressed phytoplankton cells also exhibited cell lysis followed by free release of phycobilins. The sequence of cytotoxic effects elucidated here suggests that fatty acids primarily affect the plasma membranes, leading to a change in membrane permeability and dissociation of phycobilins from the thylakoids. Severe damage to the plasma membranes would give rise to a disruption of the stressed cells.


Assuntos
Anabaena/efeitos dos fármacos , Clorófitas/efeitos dos fármacos , Ácidos Graxos não Esterificados/toxicidade , Fitoplâncton/efeitos dos fármacos , Anabaena/ultraestrutura , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Chlorella vulgaris/efeitos dos fármacos , Chlorella vulgaris/ultraestrutura , Clorófitas/ultraestrutura , Concentração Inibidora 50 , Ficocianina/análise , Fitoplâncton/ultraestrutura , Potássio/análise , Fatores de Tempo
13.
Mol Cancer Ther ; 15(2): 276-86, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26772202

RESUMO

Tumor hypoxia is associated with radioresistance, chemoresistance, and metastasis, which eventually lead to cancer progression and a poor patient prognosis. RON [also known as macrophage-stimulating protein receptor (MST1R)] belongs to the c-MET [also known as hepatocyte growth factor receptor (HGFR)] receptor tyrosine kinase (RTK) superfamily. To identify the interaction partners of RON nuclear translocation in response to hypoxia, the nuclear extract of TSGH8301 bladder cancer cells was immunoprecipitated for tandem mass profiling analysis. Nuclear RON interacted with adenosine triphosphate (ATP)-dependent DNA helicase 2 (Ku70) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to activate nonhomologous end joining (NHEJ) DNA repair. The interaction was time dependent, extending 3 to 24 hours posthypoxia or until the components had been exposed to the chemotherapeutic drugs doxorubicin and epirubicin. Stable knockdown experiments in vitro suggest the importance of RON for the chemoresistance of cancer cells under hypoxia. In addition, the tyrosine kinase domain of nuclear RON is crucial for interaction with Ku70 under hypoxia. J82 cells transfected with RON showed a survival advantage in the presence of epirubicin and hypoxia. This suggests that nuclear RON activates NHEJ repair by interacting with Ku70/DNA-PKcs and inhibiting RON activity to increase cancer cell chemosensitivity. Mol Cancer Ther; 15(2); 276-86. ©2016 AACR.


Assuntos
Antígenos Nucleares/metabolismo , Núcleo Celular/metabolismo , Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteínas Nucleares/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Reparo do DNA por Junção de Extremidades , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epirubicina/farmacologia , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Autoantígeno Ku , Transporte Proteico , Receptores Proteína Tirosina Quinases/química , Receptores Proteína Tirosina Quinases/genética , Espectrometria de Massas em Tandem
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