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1.
Chemistry ; 28(5): e202102990, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34792222

RESUMO

In recent years, molecular ferroelectrics have received great attention due to their low weight, mechanical flexibility, easy preparation and excellent ferroelectric properties. Among them, crown-ether-based molecular ferroelectrics, which are typically composed of the host crown ethers, the guest cations anchored in the crown ethers, and the counterions, are of great interest because of the host-guest structure. Such a structure allows the components to occur order-disorder transition easily, which is beneficial for inducing ferroelectric phase transition. Herein, we summarized the research progress of crown ether host-guest molecular ferroelectrics, focusing on their crystal structure, phase transition, ferroelectric-related properties. In view of the small spontaneous polarization and uniaxial nature, we outlook the chemical design strategies for obtaining high-performance crown-ether-based molecular ferroelectrics. This minireview will be of guiding significance for the future exploration of crown ether host-guest molecular ferroelectrics.

2.
Biol Chem ; 400(7): 951-963, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-30771276

RESUMO

Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we show that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3'-untranslated region (3'UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating a positive role of hnRNPK in the regulation of GSN expression. Furthermore, hnRNPK knockdown affected the migration ability of H1299 and A549 cells which could be rescued by ectopic expression of GSN in those cells. Conversely, GSN knockdown in hnRNPK-overexpressing cells could abort the stimulatory effect of hnRNPK on the cell migration. These results suggest that hnRNPK function in the regulation of cell migration is GSN-dependent. Taken together, these data unveiled a new mechanism of regulation of the GSN expression by hnRNPK and provides new clues for the discovery of new anti-metastatic therapy.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Gelsolina/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Neoplasias Pulmonares/metabolismo , RNA Mensageiro/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metástase Neoplásica
3.
Acta Biochim Biophys Sin (Shanghai) ; 51(7): 677-687, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31187136

RESUMO

Lung cancer is the leading cause of cancer death worldwide, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of diagnostic cases. The molecular mechanisms of NSCLC pathogenesis are not well understood. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein that regulates gene expression and signal transduction and closely associated with tumorigenesis, but its mechanism of action in the pathogenesis of NSCLC is unclear. In this study, we observed that the expression pattern of hnRNPK in H1299 lung adenocarcinoma cells varied depending on the cell density in culture. Moreover, hnRNPK stimulated the ability of proliferation and colony formation of H1299 cells, which is important for the multilayered cell growth in culture. We further investigated whether there is an association between hnRNPK and the elements involved in the cell contact inhibition pathway. By using quantitative reverse transcriptase-polymerase chain reaction assay and a YAP activity reporter system, we found that hnRNPK upregulated the mRNA and protein levels and transcriptional activity of Yes-associated protein 1 (YAP), a master negative regulator of Hippo contact inhibition pathway. Furthermore, YAP knockdown with siRNA abolished the stimulatory effect of hnRNPK on H1299 cell proliferation. These results suggested that YAP could be one of the effectors of hnRNPK. Our data may provide new clues for further understanding the biological functions of hnRNPK, particularly in the context of lung adenocarcinoma oncogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição/genética , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Interferência de RNA , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP
4.
Biomed Environ Sci ; 31(3): 186-196, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29673441

RESUMO

OBJECTIVE: Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation. METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened. Co-immunoprecipitation was coupled with LCMS/MS analysis to identify novel interacting partners of TRIM21. Co-immunoprecipitation and bimolecular fluorescence complementation (BIFC) were performed to validate the interactions between TRIM21 and its novel partner YWHAZ. A TRIM21-ΔRING construct was generated to test the effects of TRIM21 ligase activity on YWHAZ. RESULTS: TRIM21 positively regulated osteosarcoma cell proliferation. Overexpression of TRIM21 enhanced osteosarcoma cell tolerance toward various stresses. YWHAZ protein was identified as a novel interacting partner of TRIM21 and its expression levels were negatively regulated by TRIM21. The RING domain of TRIM21 was required for TRIM21 negative regulation of YWHAZ expression. However, overexpression of YWHAZ did not affect positive regulation of osteosarcoma cell proliferation by TRIM21. CONCLUSION: Our results further clarify the molecular mechanisms underlying the pathogenesis of osteosarcoma.


Assuntos
Proteínas 14-3-3/genética , Proliferação de Células/genética , Osteossarcoma/genética , Ribonucleoproteínas/genética , Proteínas 14-3-3/metabolismo , Humanos , Ribonucleoproteínas/metabolismo , Células Tumorais Cultivadas
5.
Ren Fail ; 38(10): 1594-1600, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27771983

RESUMO

OBJECTIVE: In this retrospective matched-cohort study, the association between potassium supplementation and long-term outcomes was determined. METHODS: Chronic peritoneal dialysis (PD) patients, aged ≥ 16 years, being referred to four PD centers in China, with serum potassium levels ≤ 3.5 mEq/L on three consecutive monthly in Q4 2008 and without receiving oral potassium supplementation in the prior three months were included in this study. Patients were divided into two groups, either to receive (test group) or not (control group) oral potassium supplementation in both Q4 2008 and the subsequent follow-up period, until 31 December 2014. The patients from the test group were matched to those from the control group using a propensity score. The clinical outcomes for all-cause and cardiovascular mortality were estimated by Matched Cox regression models during 61.5 months of median follow-up. All patients were also categorized according to serum potassium correction levels (<3.0, 3.0 to <4.0, 4.0 to <5.0 and ≥5.0 mEq/L) after the whole follow-up. The hazard ratios (HRs) were used to assess the relationship between corrected potassium levels and all-cause and cardiovascular mortality in PD patients. Subgroup analysis was used to determine the homogeneity of the associations between potassium supplementation and all-cause mortality. RESULTS: All-cause mortality occurred in 108 patients (605/10,000 person-years) in the test group and 114 patients (677/10,000 person-years) in the control group during 1786- and 1685-year follow-up, respectively [hazard ratio (HR), 0.89; 95% confidence interval (CI), 0.68-1.16; p = 0.38]. Cardiovascular mortality occurred in 97 patients (542/10,000 person-years) in the test group and 101 patients (598/10,000 person-years) in the control group (HR, 0.89; 95% CI, 0.67-1.18; p = 0.43). There were no significant interactions between potassium supplementation and any of the subgroups, except for diabetes mellitus and volume overload. During a median follow-up of 61.5 months, adjusted all-cause mortality hazard ratio (HR) and 95% confidence interval (CI) for corrected serum potassium of <3.0, 3.0 to < 4.0, and ≥5.0 mEq/L, compared with 4.0 to < 5.0 mEq/L (reference), were 2.23 (1.17-3.72), 1.35 (0.89-1.81), and 1.74 (1.05-3.72), respectively. CONCLUSION: The use of potassium supplementation in chronic PD patients is not associated with mortality. While it may be necessary for the correction of hypokalemia or the maintenance of normokalemia, and the consequent reduction of hypokalemia-associated mortality. Additionally, use of aldosterone antagonists may be preferable for the handling of hypokalemia in PD patients.


Assuntos
Insuficiência Cardíaca/mortalidade , Hipopotassemia/epidemiologia , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Potássio/administração & dosagem , Potássio/sangue , Adulto , Idoso , Causas de Morte , China , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Hipopotassemia/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
6.
J Recept Signal Transduct Res ; 35(2): 133-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25007156

RESUMO

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease (ESRD) from the published reports is still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the iPTH level among patients with ESRD. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with iPTH level among patients with ESRD. In this meta-analysis, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations (Bb versus bb: OR = 61.40, 95% CI: 19.65-103.16, p = 0.004). However, the iPTH level in ESRD patients carrying BB genotype was not significant different from that in ESRD patients with Bb genotype and bb genotype in overall populations (BB versus Bb: OR = -18.30, 95% CI: -126.28-89.69, p = 0.74; BB versus bb: OR = 22.85, 95% CI: -70.81-116.51, p = 0.63). Furthermore, the results for Caucasians were similar to those in overall populations. In conclusion, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations and in Caucasians. However, more studies should be conducted to confirm it.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Falência Renal Crônica/genética , Hormônio Paratireóideo/genética , Genótipo , Humanos , Falência Renal Crônica/patologia , Fatores de Risco , População Branca
7.
Ren Fail ; 37(5): 804-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25707516

RESUMO

OBJECTIVE: To explore the relation between the frequencies of apolipoprotein E (ApoE) alleles and the occurrence of depression in patients undergoing hemodialysis in a Chinese population. METHODS: We examined the ApoE alleles in a sample of 288 subjects: 72 patients with depression under hemodialysis, 74 patients without depression under hemodialysis, 75 patients with depression under nondialytic treatment and 67 patients without depression under nondialytic treatment. The depression state was assessed using the Center for Epidemiological Studies Depression (CES-D) scale. Associations between the occurrence of depression and the frequencies of ApoE alleles were examined using multinomial logistic regression models with adjustment of relevant covariates. Information about sociodemographics, clinical data, vascular risk factors and cognitive function was also collected and evaluated. RESULTS: The frequencies of ApoE-ɛ2 were significantly different between depressed and non-depressed patients irrespective of dialysis (p < 0.05), but no significant difference was found in the frequencies of ApoE-ɛ4 (p > 0.05). Serum ApoE levels were significantly different between depressed and non-depressed patients in the whole sample (p < 0.05). Multinomial logistic regression models showed significant association between the frequency of ApoE-ɛ2 and the occurrence of depression in the Chinese population after control of relevant covariates, including age, sex, educational level, history of smoking and drinking, vascular risk factors and cognitive function. CONCLUSIONS: No association between the frequency of ApoE-ɛ4 and the occurrence of depression was found in patients undergoing hemodialysis. Further research is needed to find out if ApoE-ɛ2 acts as a protective factor in Chinese dialysis population since it might decrease the prevalence of depression and delay the onset age.


Assuntos
Apolipoproteína E2/sangue , Apolipoproteína E4/sangue , Depressão/genética , Falência Renal Crônica/psicologia , Diálise Renal/métodos , Adulto , Alelos , Povo Asiático , Estudos de Casos e Controles , China , Cognição , Depressão/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Falência Renal Crônica/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
J Biol Chem ; 288(23): 16588-16597, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23612971

RESUMO

pVHL, the product of von Hippel-Lindau (VHL) tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase complex that targets hypoxia inducible factor α (HIF-α) for ubiquitination and degradation. Besides HIF-α, pVHL also interacts with other proteins and has multiple functions. Here, we report that pVHL inhibits ribosome biogenesis and protein synthesis. We find that pVHL associates with the 40S ribosomal protein S3 (RPS3) but does not target it for destruction. Rather, the pVHL-RPS3 association interferes with the interaction between RPS3 and RPS2. Expression of pVHL also leads to nuclear retention of pre-40S ribosomal subunits, diminishing polysomes and 18S rRNA levels. We also demonstrate that pVHL suppresses both cap-dependent and cap-independent protein synthesis. Our findings unravel a novel function of pVHL and provide insight into the regulation of ribosome biogenesis by the tumor suppressor pVHL.


Assuntos
Polirribossomos/metabolismo , Biossíntese de Proteínas/fisiologia , RNA Ribossômico 18S/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/biossíntese , Linhagem Celular Tumoral , Humanos , Polirribossomos/genética , RNA Ribossômico 18S/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(1): 35-9, 2014 Jan.
Artigo em Zh | MEDLINE | ID: mdl-24461175

RESUMO

OBJECTIVE: This study aimed to evaluate the effectiveness of multi-disciplinary treatment approaches in reducing neurological disabilities in premature infants. METHODS: A total of 117 infants who were born premature in our hospital between March 2008 and February 2010 but had no congenital malformations and no severe neonatal complications, were enrolled in this study. They were randomly allocated to a multi-disciplinary treatment group (n=63) and a control group (n=54). While patients in the control group underwent an early conventional treatment, those in the multi-disciplinary treatment group were subjected to regular development monitoring, neurological examination and screening for brain injury, neuro-nutrition and neurodevelopment therapies, and rehabilitation training. RESULTS: The incidence rates of abnormalities in posture, reflex, sleep, muscle tone and EEG were significantly lower in the multi-disciplinary treatment group than in the control froup (P<0.05) at corrected postnatal ages of 6-12 months. At corrected postnatal ages of 6, 12, 18 and 24 months, both mental development index (MDI) and psychomotor development index (PDI) scores were significantly higher in the multi-disciplinary treatment group than in the control group (P<0.05). At corrected postnatal age of 3 years, incidence rates of cerebral palsy, language barrier, abnormal muscle tone and hearing impairment were significantly lower in the multi-disciplinary treatment group than in the control group (P<0.05). CONCLUSIONS: Early multi-disciplinary intervention approaches may significantly improve mental and motor developments and reduce the incidence of cerebral palsy-associated neurological disabilities in premature infants.


Assuntos
Deficiências do Desenvolvimento/prevenção & controle , Doenças do Prematuro/prevenção & controle , Paralisia Cerebral/prevenção & controle , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino
10.
J Biol Chem ; 287(53): 44164-72, 2012 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-23135283

RESUMO

Paired box (PAX) 2, a transcription factor, plays a critical role in embryogenesis. When aberrantly expressed in adult tissues, it generally exhibits oncogenic properties. However, the underlying mechanisms remain unclear. We reported previously that the expression of PAX2 was up-regulated in human colon cancers. However, the role of PAX2 in colon cancer cells has yet to be determined. The aim of this study is to determine the function of PAX2 in colon cancer cells and to investigate the possible mechanisms underlain. We find that knockdown of PAX2 inhibits proliferation and xenograft growth of colon cancer cells. Inhibition of PAX2 results in a decreased expression of cyclin D1. Expression of cyclin D1 is found increased in human primary colon malignant tumors, and its expression is associated with that of PAX2. These data indicate that PAX2 is a positive regulator of expression of cyclin D1. We find that knockdown of PAX2 inhibits the activity of AP-1, a transcription factor that induces cyclin D1 expression, implying that PAX2 induces cyclin D1 through AP-1. PAX2 has little effect on expression of AP-1 members including c-Jun, c-Fos, and JunB. Our data show that PAX2 prevents JunB from binding c-Jun and enhances phosphorylation of c-Jun, which may elevate the activity of AP-1. Taken together, these results suggest that PAX2 promotes proliferation of colon cancer cells through AP-1.


Assuntos
Proliferação de Células , Neoplasias do Colo/metabolismo , Ciclina D1/genética , Fator de Transcrição PAX2/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Regulação para Cima , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/fisiopatologia , Ciclina D1/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator de Transcrição PAX2/genética , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/genética , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo
11.
Acta Pharmacol Sin ; 34(3): 414-23, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23377547

RESUMO

AIM: To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function. METHODS: SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad. After the onset of AA, the rats were injected BF02 (1, 3, or 9 mg/kg, sc) every 3 d for a total of 15 d. Intragastric administration of methotrexate (MTX, 0.5 mg/kg, every 3 d for a total of 15 d) was taken as the positive control drug. Arthritis index, swollen joint count, ankle joint histopathology, spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats. T lymphocyte function was assessed by measuring T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression levels, and percentage of T lymphocyte subsets. RESULTS: In the AA rats, remarkable secondary inflammatory responses exhibited, accompanied by significantly higher levels of IL-1, IL-6, TNF-α, IL-17, LTα, RANKL, and MMP-13. The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats. The percentages of CD3(+)CD4(+) and CD4(+)CD25(+) T lymphocytes were increased, whereas the percentages of CD4(+)CD62L(+) and CD4(+)CD25(+)FoxP3(+) T lymphocytes were decreased. Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index, swollen joint count and arthritis global assessment. Moreover, both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation, and blocked the above mentioned aberrance in T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression, and percentages of T lymphocyte subsets. CONCLUSION: BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Receptores Tipo II do Fator de Necrose Tumoral/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Animais , Antirreumáticos/administração & dosagem , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Experimental/radioterapia , Artrografia , Proliferação de Células/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Articulações/efeitos dos fármacos , Articulações/imunologia , Articulações/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Tipo II do Fator de Necrose Tumoral/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Timo/efeitos dos fármacos , Timo/imunologia , Timo/patologia
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 14(2): 139-43, 2012 Feb.
Artigo em Zh | MEDLINE | ID: mdl-22357475

RESUMO

OBJECTIVE: To study the effects of environmental enrichment on neuron proliferation, learning and memory ability and motor ability in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: One hundred and eight 7-day-old Sprague-Dawley rats were randomly divided into three groups: sham operation (CON group), HIBD and intervention group. HIBD model was prepared according to the classic Rice-Vannucci method. Environmental enrichment was administered for the rats in the intervention group after HIBD inducement. Behavioral tests (Water maze test, Suspension test and Slope test) were performed and the number of neural cells in the left hippocampus was examined 7, 14 and 28 days after intervention. RESULTS: The pyramid cells in the hippocampus CA1 area in the HIBD group were significantly less than in the CON group at 7, 14 and 28 days (P<0.05). The number of pyramid cells in the hippocampus CA1 area in the intervention group was significantly higher than in the HIBD group (P<0.01) at 7, 14 and 28 days. The hidden platform escape latency period (EL) in the Water maze test was significantly more prolonged and the cross-platform number within 2 minutes was significantly less in the HIBD and the intervention groups than in the CON group at all observed time points (P<0.01). The EL was significantly shorter and the cross-platform number within 2 minutes was significantly higher in the intervention group than in the HIBD group at all observed time points (P<0.01). The maintain time and score in the Suspension test were significantly lower and the time in the Slope test was significantly more prolonged in the HIBD and intervention groups than in the CON group at 7, 14 and 28 days (P<0.01). An increased maintain time and score and a decreased time in the Slope test were found in the intervention group compared with the HIBD group at 14 and 28 days (P<0.01). CONCLUSIONS: Environmental enrichment can improve motor function, learning and memory ability, and promote the repair and proliferation of neurons in neonatal rats with HIBD.


Assuntos
Proliferação de Células , Hipóxia-Isquemia Encefálica/fisiopatologia , Neurônios/fisiologia , Animais , Animais Recém-Nascidos , Meio Ambiente , Feminino , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto , Atividade Motora , Ratos , Ratos Sprague-Dawley
13.
Chem Commun (Camb) ; 58(33): 5148-5151, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35383794

RESUMO

We discovered that [(histamine)(18-crown-6)2][BF4]2 is a high-temperature host-guest inclusion complex that presents decent piezoelectric properties (d33 = 5 pC/N), undergoes a phase transition at 406 K, and also possesses potential ferroelectricity. This work provides a new idea for constructing host-guest inclusion piezoelectrics.


Assuntos
Éteres de Coroa , Histamina , Transição de Fase , Temperatura
14.
Cell Death Dis ; 12(1): 21, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33414451

RESUMO

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, which is characterized by dysfunctional autophagy and poor differentiation. Our recent studies have suggested that the tripartite motif containing-21 (TRIM21) plays a crucial role in regulating OS cell senescence and proliferation via interactions with several proteins. Yet, its implication in autophagy and differentiation in OS is largely unknown. In the present study, we first showed that TRIM21 could promote OS cell autophagy, as determined by the accumulation of LC3-II, and the degradation of cargo receptor p62. Further, we were able to identify that Annexin A2 (ANXA2), as a novel interacting partner of TRIM21, was critical for TIRM21-induced OS cell autophagy. Although TRIM21 had a negligible effect on the mRNA and protein expressions of ANXA2, we did find that TRIM21 facilitated the translocation of ANXA2 toward plasma membrane (PM) in OS cells through a manner relying on TRIM21-mediated cell autophagy. This functional link has been confirmed by observing a nice co-expression of TRIM21 and ANXA2 (at the PM) in the OS tissues. Mechanistically, we demonstrated that TRIM21, via facilitating the ANXA2 trafficking at the PM, enabled to release the transcription factor EB (TFEB, a master regulator of autophagy) from the ANXA2-TFEB complex, which in turn entered into the nucleus for the regulation of OS cell autophagy. In accord with previous findings that autophagy plays a critical role in the control of differentiation, we also demonstrated that autophagy inhibited OS cell differentiation, and that the TRIM21/ANXA2/TFEB axis is implicated in OS cell differentiation through the coordination with autophagy. Taken together, our results suggest that the TRIM21/ANXA2/TFEB axis is involved in OS cell autophagy and subsequent differentiation, indicating that targeting this signaling axis might lead to a new clue for OS treatment.


Assuntos
Oncogenes/genética , Osteossarcoma/genética , Ribonucleoproteínas/metabolismo , Anexina A2/metabolismo , Autofagia , Diferenciação Celular , Linhagem Celular Tumoral , Humanos , Transdução de Sinais
15.
Mitochondrial DNA B Resour ; 6(1): 99-101, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33537415

RESUMO

Huainan Partridge chicken is one of the indigenous chicken breeds in China. In this study, the first complete mitochondrial DNA (mtDNA) sequence of Huainan Partridge chicken had been obtained using PCR amplification, sequencing and assembling. The mitogenome of Huainan Partridge chicken is 16785 bp in length, including a control region (D-loop), 13 protein-coding genes, 22 transfer genes and 2 ribosomal genes. The base composition of the complete mtDNA sequence is 30.27% for A, 23.73% for T, 13.50%for G, 32.50% for C. This study will provide reference for the phylogenetic analysis of Huainan Partridge chicken.

16.
Biosci Rep ; 40(6)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32515466

RESUMO

In the present study, we examined the molecular mechanism of astragaloside IV (AS-IV) in high glucose (HG)-induced epithelial-to-mesenchymal transition (EMT) in renal proximal tubular epithelial cells (PTCs). NRK-52E cell viability and apoptosis were determined by the cell counting kit-8 (CCK-8) assay and flow cytometric analysis, respectively. Expressions of E-cadherin, N-cadherin, vimentin, and occludin were measured by Western blot, and those of E-cadherin and N-cadherin were additionally measured by immunofluorescence analysis. Transforming growth factor-ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The expressions of Smad2, Smad3, phosphorylated-Smad2 (p-Smad2), and p-Smad3 were measured using Western blot. We found that AS-IV could recover NRK-52E cell viability and inhibit HG-induced cell apoptosis. TGF-ß1, α-SMA, Smad2, Smad3, p-Smad2, and p-Smad3 expressions were decreased in the AS-IV-treated groups compared with the HG group. Moreover, the expressions of E-cadherin and occludin were remarkably up-regulated and those of N-cadherin and vimentin were down-regulated in the AS-IV-treated groups compared with the HG group. Interestingly, the TGF-ß1 activator SRI-011381 hydrochloride had an antagonistic effect to AS-IV on HG-induced EMT behavior. In conclusion, AS-IV attenuates HG-induced EMT by inhibiting the TGF-ß/Smad pathway in renal PTCs.


Assuntos
Nefropatias Diabéticas/prevenção & controle , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/toxicidade , Túbulos Renais Proximais/efeitos dos fármacos , Saponinas/farmacologia , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Triterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Linhagem Celular , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Proteínas do Tecido Nervoso/metabolismo , Ocludina/metabolismo , Fosforilação , Ratos , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Vimentina/metabolismo
17.
Inflamm Res ; 58(8): 473-82, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19271152

RESUMO

OBJECTIVE: Activation of Toll-like receptor 4 (TLR4) in peritoneal mesothelial cells by endotoxin contributes to peritoneal inflammation and fibrosis. Here we investigated TLR4 expression induced by angiotensin II (Ang II) and functional consequences of nuclear factor-kappaB (NF-kappaB) activation and CD40 expression in rat peritoneal mesothelial cells (RPMCs). METHODS: TLR4, CD40, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were determined by reverse transcription polymerase chain reaction (RT-PCR) and TLR4, IkappaBalpha, phospho-IkappaBalpha, NF-kappaB p65, and phospho-NF-kappaB p65 were analyzed by Western blot. The intracellular distribution of NF-kappaB p65 was detected by immunofluorescence. RESULTS: Treatment of RPMCs with Ang II resulted in an increase in the expression of TLR4 mRNA and protein levels. Preincubation of RPMCs with Ang II significantly increased lipopolysaccharide (LPS)-induced phospho-IkappaBalpha and phospho-NF-kappaB p65 protein (P < 0.05 vs. LPS alone) and CD40, TNF-alpha, and IL-6 mRNA levels (P < 0.05 vs. LPS alone). A significantly increased nuclear staining of NF-kappaB p65 in cells treated with Ang II plus LPS was also observed. CONCLUSIONS: Ang II upregulates the expression of TLR4 by RPMCs, resulting in enhanced NF-kappaB signaling and induction of CD40, TNF-alpha, and IL-6 expression. Locally produced Ang II in the peritoneum may have an amplified role in LPS-induced peritoneal inflammation.


Assuntos
Angiotensina II/farmacologia , Antígenos CD40/biossíntese , Lipopolissacarídeos/farmacologia , Receptor 4 Toll-Like/efeitos dos fármacos , Animais , Western Blotting , Epitélio/efeitos dos fármacos , Interleucina-6/biossíntese , Masculino , Microscopia de Fluorescência , NF-kappa B/metabolismo , Peritônio/citologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/biossíntese
18.
Int Immunopharmacol ; 66: 198-204, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30471618

RESUMO

BACKGROUND: It has been demonstrated that thioredoxin-interacting protein (TXNIP) interacted with NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and participated in the NLRP3 inflammasome activation. Our previous study has demonstrated that in human peritoneal mesothelial cells (HPMCs), exposure to high glucose-based peritoneal dialysis (PD) solutions induced mitochondrial reactive oxygen species (ROS) production, activation of NLRP3 inflammasome and IL-1ß expression. This study aimed to investigate the effect of high glucose-based PD fluids on the TXNIP expression and the underlying mechanisms by which TXNIP-NLRP3 interaction mediates the inflammatory injury to HPMCs in high glucose-based PD fluids conditions. METHODS: TXNIP gene and protein expression was detected by real-time polymerase chain reaction (RT-PCR) and immunoblot. Immunoprecipitation was used to evaluate the interaction between TRX1 and TXNIP, TXNIP and NLRP3. ROS production and IL-1ß expression was examined by flow cytometry and immunoblot and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: It was identified that high glucose-based PD solutions enhance the level of TXNIP gene and protein in cultured HPMCs and a rat-based PD model. We also found that ROS generation induced by high glucose-based PD solutions disrupts the TRX1-TXNIP association, while promoting the binding of TXNIP to NLRP3 in HPMCs. Furthermore, the application of a ROS inhibitor (APDC) to HPMCs blocked the high glucose-based PD solution-induced TXNIP-NLRP3 binding, in addition to ROS production and IL-1ß expression. CONCLUSION: The results of the present study revealed a novel mechanism underlying high glucose-containing PD-mediated peritoneal inflammatory injury, supporting the attenuation of ROS generation as a potential therapeutic strategy to alleviate such pathology.


Assuntos
Proteínas de Transporte/metabolismo , Epitélio/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/metabolismo , Falência Renal Crônica/terapia , Diálise Peritoneal , Peritônio/patologia , Animais , Proteínas de Transporte/genética , Linhagem Celular , Modelos Animais de Doenças , Epitélio/metabolismo , Epitélio/patologia , Glucose , Humanos , Interleucina-1beta/metabolismo , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Regulação para Cima
19.
FEBS Open Bio ; 9(3): 468-477, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30868055

RESUMO

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are recurrent diseases that are widespread in the tropics. Here, we identified candidate genes associated with these diseases by performing integrated analyses of DF (GSE51808) and DHF (GSE18090) microarray datasets in the Gene Expression Omnibus (GEO). In all, we identified 7635 differentially expressed genes (DEGs) in DF and 8147 DEGs in DHF as compared to healthy controls (P < 0.05). In addition, we discovered 215 differentially expressed long non-coding RNAs (DElncRNAs) in DF and 225 DElncRNAs in DHF. There were 1256 common DEGs and eight common DElncRNAs in DHF vs DF, DHF vs normal control, and DF vs normal control groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that signal transduction (false discovery rate = 8.33E-10), 'toxoplasmosis', and 'protein processing in endoplasmic reticulum' were significantly enriched pathways for common DEGs. We conclude that the MAGED1,STAT1, and IL12A genes may play crucial roles in DF and DHF, and suggest that our findings may facilitate the identification of biomarkers and the development of new drug design strategies for DF and DHF treatment.


Assuntos
Dengue/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Dengue Grave/genética , Biomarcadores/análise , Perfilação da Expressão Gênica , Humanos
20.
Biomed Pharmacother ; 108: 1651-1657, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372867

RESUMO

Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), is an active monomer obtained by modifying the structure of paeoniflorin (Pae). CP-25 can alleviate the course of adjuvant arthritis (AA) rats by regulating immune inflammatory response and reducing bone damage. In addition, our research has found that immune cells are important target cells for its anti-inflammatory and immunomodulatory effects. Therefore, it is of great significance to study the pharmacokinetics of CP-25 in immune cells. The aim of this study was to investigate the absorption and efflux of CP-25 in plasma and peripheral blood mononuclear cells (PBMCs) of rats. We established a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to rapidly determine CP-25 in plasma and PBMC of rat. We found that the transport amount of CP-25 in PBMC gradually decreased with the increase of time, and reached equilibrium after 1 h. Moreover, there is a certain correlation between the concentration of CP-25 in plasma and the concentration of CP-25 in PBMC. In addition, we used several transporter inhibitors to study their effects on the efflux of CP-25 in PBMC. The efflux of CP-25 in PBMC increased with the increase of time in the first 30 min, and the efflux of CP-25 decreased gradually after 30 min. Furthermore, after multiple administration of 50 mg/kg in rats, concentration of CP-25 in PBMC is similar to the change of concentration of CP-25 in plasma. Our results suggest that CP-25 may enter PBMC by passive transport, and P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) may be involved in the efflux of CP-25 in PBMC. This research provides a basis and guidance for further study of the clinical application of CP-25.


Assuntos
Absorção Fisiológica , Glucosídeos/sangue , Leucócitos Mononucleares/metabolismo , Monoterpenos/sangue , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Transporte Biológico , Cromatografia Líquida de Alta Pressão , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Modelos Lineares , Masculino , Proteínas de Membrana/metabolismo , Monoterpenos/administração & dosagem , Monoterpenos/farmacocinética , Ratos Sprague-Dawley , Temperatura , Fatores de Tempo
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