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1.
Mar Drugs ; 22(1)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38248672

RESUMO

Macroalgae, particularly red seaweeds, have attracted significant attention due to their economic and health benefits. Chondrus, a red algae genus, despite its economic importance, seems to be undervalued. Among all its species, Chondrus crispus has been meticulously documented for its biological properties, and little is known about other species. No comprehensive review of the biological properties of this genus has been acknowledged. Thus, this review aimed to summarize the available information on the chemical constituents and biological properties of a few selected species, including Chondrus crispus, Chondrus ocellatus, Mazzaella canaliculata, and Chondrus armatus. We compiled and discovered that the genus is offering most of the important health-promoting benefits evidenced from in vitro and in vivo studies focused on antimicrobial, immunomodulation, neuroprotection, anti-atopic, anti-inflammatory, anti-viral, anti-diabetic, cytoprotective, antioxidant, anti-coagulation, nephroprotective, anti-tumor, and anti-venom activity, which speaks about the potential of this genus. Data on clinical studies are limited. Further, around 105 chemical constituents have been reported from Chondrus spp. Given its significance, further investigation is warranted, in the form of meticulously planned cell, animal, and clinical studies that concentrate on novel health-enhancing endeavors, in order to unveil the full potential of this genus. The review also outlines challenges and future directions.


Assuntos
Chondrus , Hipersensibilidade Imediata , Alga Marinha , Animais , Antioxidantes/farmacologia , Antivenenos
2.
Cutan Ocul Toxicol ; 42(4): 283-291, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37675483

RESUMO

Introduction: Ophthalmic sponges are used for cleaning the eye surface and absorbing fluids during ophthalmic procedures. This study compared the biological safety and stability of a new ophthalmic sponge, Occucell® (OccuTech Inc, Seongnam, Korea), on the human conjunctival epithelial cells with those of preexisting products to evaluate its clinical application.Materials and Methods: The cytotoxicity of four products, Occucell, a new product, Ultracell®, Eyetec-1, and Eyetec-2, on conjunctival epithelial cells, was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) analysis. Additionally, human conjunctival epithelial cells were stained with a Live & Dead marker and observed using a fluorescence microscope. To evaluate the effect of the ophthalmic sponges on the secretion of IL-1ß and TNF-α, cultured conjunctival epithelial cells were treated with 0.5% DMSO eluates of the ophthalmic sponges, and IL-1ß and TNF-α mRNA levels were estimated using real-time polymerase chain reaction assays.Results: Cells treated with Occucell showed comparable viability to those treated with other preexisting products. Conjunctival epithelial cells showed more than 90% viability when treated with the ophthalmic sponge extracts, as determined by the MTT assay. No significant differences in the number of live & dead cells were observed between the control and treatment groups. Cells treated with all four ophthalmic sponge eluates showed similar IL-1ß and TNF-α mRNA levels.Discussion: Occucell, an eye sponge used during ophthalmic surgery in clinical practice, did not affect the viability of conjunctival epithelial cells, and more than 90% of the cells were viable after the treatment. Further, Occucell showed similar effects on IL-1ß and TNF-α secretion as that of other ophthalmic sponges used in the clinic. This suggested that Occucell is a safe product comparable to the preexisting products.


Assuntos
Túnica Conjuntiva , Fator de Necrose Tumoral alfa , Humanos , Células Epiteliais , RNA Mensageiro
3.
Nutrients ; 15(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36839367

RESUMO

Patients with cancer need to maintain proper nutritional status to overcome cancer, alleviate the side effects of chemotherapy, and prevent a recurrence. As such, it is necessary to manage nutritional status. This study aimed to develop a dish-based semi-quantitative food frequency questionnaire (FFQ) to evaluate the nutritional status of patients with cancer and assess the validity of the FFQ. A total of 109 dish items were selected through contribution and variability analyses using the 2016-2018 Korea National Health and Nutrition Examination Survey data. The FFQ was validated against the average 3-day dietary records of 100 patients with cancer. Pearson correlation coefficients and quartile agreements between FFQ and 3-day dietary records were calculated for intake of energy, macronutrients, and micronutrients. Age and energy-adjusted Pearson correlation coefficients ranged from 0.20 (iron) to 0.54 (potassium). The percentage of participants who were classified into the same or adjacent quartile between the FFQ and the 3-day dietary record ranged from 68% (protein) to 81% (energy, dietary fiber). The results suggest that the FFQ is an appropriate tool for assessing nutritional status in Korean cancer patients.


Assuntos
Neoplasias , Estado Nutricional , Humanos , Dieta , Inquéritos Nutricionais , Inquéritos e Questionários , Inquéritos sobre Dietas , Reprodutibilidade dos Testes , Registros de Dieta , Ingestão de Energia
4.
Antioxidants (Basel) ; 9(12)2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33291467

RESUMO

Amaranth (Amaranthus spp.) plant commonly refers to the sustainable food crop for the 21st century. The crop has witnessed significant attention in recent years due to its high nutritional value and agronomic advantages. It is a relatively well-balanced cosmopolitan food that is a protector against chronic diseases. Usually, the antioxidant activities of amaranth are held responsible for its defensive behavior. Antioxidant activity of plants, generally, is attributed to their phytochemical compounds. The current interest, however, lies in hydrolysates and bioactive peptides because of their numerous biological functions, including antioxidant effect. While the importance of bioactive peptides has been progressively recognized, an integrated review of recent studies on the antioxidant ability of amaranth species, especially their hydrolysates and peptides has not been generated. Hence, in this review, we summarize studies focused on the antioxidant capacity of amaranth renewal over the period 2015-2020. It starts with a background and overall image of the amaranth-related published reviews. The current research focusing on in vitro, in vivo, and chemical assays-based antioxidant activity of different amaranth species are addressed. Finally, the last segment includes the latest studies concerning free radical scavenging activity and metal chelation capacity of amaranth protein hydrolysates and bioactive peptides.

5.
Anticancer Res ; 40(6): 3239-3246, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487618

RESUMO

BACKGROUND/AIM: Non-structural maintenance of chromosomes condensin I complex subunit H (NCAPH) is implicated in correct chromosome condensation and segregation during mitosis. However, the functional role of NCAPH in the pathogenesis of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study was to elucidate the role of NCAPH in NSCLC cells. MATERIALS AND METHODS: A549 and H1299 NSCLC cells were transfected with small-interfering RNA (siRNA) against NCAPH. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-formation assay and flow cytometry analysis were performed to reveal the role of NCAPH in NSCLC cells. In addition, migration and invasion assay were also performed. RESULTS: NCAPH knockdown inhibited cell proliferation, induced cell-cycle arrest at G2/M phase, and prevented colony formation, migration and invasion by NSCLC cells. CONCLUSION: NCAPH is involved in NSCLC progression and development, and may be a potential therapeutic target for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Nucleares/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Pontos de Checagem do Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Invasividade Neoplásica , Proteínas Nucleares/biossíntese , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transfecção , Regulação para Cima
6.
Anticancer Res ; 40(5): 2601-2611, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366405

RESUMO

BACKGROUND/AIM: Alpha/beta-hydrolase domain containing 12 (ABHD12) is a serine hydrolase that regulates immunological and neurological mechanisms. This study aimed to elucidate the oncogenic effect of ABHD12 on human breast cancer. MATERIALS AND METHODS: ABHD12 expression was confirmed in breast cancer tissues and breast cancer cell lines by immunohistochemistry and quantitative RT-PCR. To determine the role of ABHD12, ABHD12 siRNA-suppressed breast cancer cells (MCF7 and MDA-MB-231 cells) were investigated for cell proliferation, migration, and invasion capabilities using MTT assays, EdU assays, colony formation assays, and Boyden chamber assays. RESULTS: Immunohistochemical staining showed a higher ABHD12 expression in breast cancer tissues than in normal tissues. Additionally, ABHD12 knockdown was found to inhibit cell growth, proliferation, migration, and invasion in breast cancer cells. CONCLUSION: ABHD12 plays a crucial role in cell proliferation, migration, and invasion of breast cancer cells.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular , Técnicas de Silenciamento de Genes , Monoacilglicerol Lipases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Monoacilglicerol Lipases/genética , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Receptores de Canabinoides/metabolismo , Regulação para Cima/genética
7.
Korean J Physiol Pharmacol ; 24(3): 267-276, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32392918

RESUMO

In the present study, we investigated the effect of oncogenic H-Ras on rat mdr1b expression in NIH3T3 cells. The constitutive expression of H-RasV12 was found to downregulate the mdr1b promoter activity and mdr1b mRNA expression. The doxorubicin-induced mdr1b promoter activity of the H-RasV12 expressing NIH3T3 cells was markedly lower than that of control NIH3T3 cells. Additionally, there is a positive correlation between the level of H-RasV12 expression and a sensitivity to doxorubicin toxicity. To examine the detailed mechanism of H-RasV12-mediated down-regulation of mdr1b expression, antioxidant N-acetylcysteine (NAC) and NADPH oxidase inhibitor diphenylene iodonium (DPI) were used. Pretreating cells with either NAC or DPI significantly enhanced the oncogenic H-Ras-mediated down-regulation of mdr1b expression and markedly prevented doxorubicin-induced cell death. Moreover, NAC and DPI treatment led to a decrease in ERK activity, and the ERK inhibitors PD98059 or U0126 enhanced the mdr1b-Luc activity of H-RasV12-NIH3T3 and reduced doxorubicin-induced apoptosis. These data suggest that RasV12 expression could downregulate mdr1b expression through intracellular reactive oxygen species (ROS) production, and ERK activation induced by ROS, is at least in part, contributed to the downregulation of mdr1b expression.

8.
Int J Mol Sci ; 21(7)2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32290222

RESUMO

Mediator of DNA damage checkpoint protein 1 (MDC1) plays a vital role in DNA damage response (DDR) by coordinating the repair of double strand breaks (DSBs). Here, we identified a novel interaction between MDC1 and karyopherin α-2 (KPNA2), a nucleocytoplasmic transport adaptor, and showed that KPNA2 is necessary for MDC1 nuclear import. Thereafter, we identified a functional nuclear localization signal (NLS) between amino acid residues 1989-1994 of the two Breast Cancer 1 (BRCA1) carboxyl-terminal (tBRCT) domain of MDC1 and demonstrated disruption of this NLS impaired interaction between MDC1 and KPNA2 and reduced nuclear localization of MDC1. In KPNA2-depleted cells, the recruitment of MDC1, along with the downstream signaling p roteins Ring Finger Protein 8 (RNF8), 53BP1-binding protein 1 (53BP1), BRCA1, and Ring Finger Protein 168 (RNF168), to DNA damage sites was abolished. Additionally, KPNA2-depleted cells had a decreased rate of homologous recombination (HR) repair. Our data suggest that KPNA2-mediated MDC1 nuclear import is important for DDR signaling and DSB repair.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Sinais de Localização Nuclear , Domínios e Motivos de Interação entre Proteínas , alfa Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas de Ciclo Celular/química , Linhagem Celular Tumoral , Dano ao DNA , Técnicas de Silenciamento de Genes , Humanos , Ligação Proteica , Reparo de DNA por Recombinação , alfa Carioferinas/genética
9.
Anticancer Res ; 40(4): 1953-1962, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234884

RESUMO

BACKGROUND/AIM: Caspase recruitment domain family, member 14 (CARD14) is a member of the CARD family of proteins, which play an important role in immune and inflammatory response, and cell survival and proliferation. Here, we identified the role of CARD14 in human breast cancer. MATERIALS AND METHODS: Immunohistochemistry was performed to evaluate CARD14 expression in breast cancer. Using CARD14 knockdown cells by small interfering RNA, colony formation and MTT assays, flow cytometry analyses, and migration assays were performed to evaluate the proliferation, cell cycle distribution, apoptosis, and migration ability of MCF7 and SK-BR-3 cells. RESULTS: CARD14 expression was significantly higher in breast cancer samples than in normal breast samples. CARD14 knockdown inhibited cell proliferation and migration, caused cell cycle arrest at the G1/S boundary, and promoted apoptosis. CONCLUSION: CARD14 regulates the proliferation and migration of MCF7 and SK-BR-3 cells; it is thus, a novel potential therapeutic target in breast cancer.


Assuntos
Neoplasias da Mama/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Movimento Celular/genética , Proliferação de Células/genética , Guanilato Ciclase/genética , Proteínas de Membrana/genética , Apoptose/genética , Neoplasias da Mama/patologia , Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , RNA Interferente Pequeno/genética
10.
Micromachines (Basel) ; 11(4)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331254

RESUMO

Stress biomarkers such as hormones and neurotransmitters in bodily fluids can indicate an individual's physical and mental state, as well as influence their quality of life and health. Thus, sensitive and rapid detection of stress biomarkers (e.g., cortisol) is important for management of various diseases with harmful symptoms, including post-traumatic stress disorder and depression. Here, we describe rapid and sensitive cortisol detection based on a conducting polymer (CP) nanotube (NT) field-effect transistor (FET) platform. The synthesized polypyrrole (PPy) NT was functionalized with the cortisol antibody immunoglobulin G (IgG) for the sensitive and specific detection of cortisol hormone. The anti-cortisol IgG was covalently attached to a basal plane of PPy NT through an amide bond between the carboxyl group of PPy NT and the amino group of anti-cortisol IgG. The resulting field-effect transistor-type biosensor was utilized to evaluate various cortisol concentrations. Cortisol was sensitively measured to a detection limit of 2.7 × 10-10 M (100 pg/mL), with a dynamic range of 2.7 × 10-10 to 10-7 M; it exhibited rapid responses (<5 s). We believe that our approach can serve as an alternative to time-consuming and labor-intensive health questionnaires; it can also be used for diagnosis of underlying stress-related disorders.

11.
J Med Food ; 23(3): 335-342, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32130058

RESUMO

This study investigated the effect of Sinetrol-XPur on weight and body fat reduction in overweight or obese Korean participants. Among 100 overweight or obese participants enrolled in a 12-week randomized, double-blinded, controlled study, 86 participants completed the trial. Participants took either two Sinetrol-XPur tablets (450 mg per tablet) or two placebo tablets once a day. Bodyweight, body fat percentage, body mass index (BMI), body fat mass, waist circumference, and various safety parameters were measured. After the 12-week intervention, a significant reduction was observed in the body fat mass (P = .030) by dual-energy X-ray absorptiometry (DEXA), body weight (P = .002), and BMI (P = .002) compared to the placebo. Body fat percentage (P = .007) by DEXA showed a significant reduction in the Sinetrol-XPur group, but no difference compared to the control group. Abdominal metabolic risks by computed tomography and blood biochemistry analysis were significantly decreased in the Sinetrol-XPur group, but there were no differences between the Sinetrol-XPur and placebo groups. Safety profiles were not different between the two groups. These results suggested that Sinetrol-XPur significantly reduced body weight, body fat mass, and BMI in obese Korean subjects, which confirms the antiobesity effect of Sinetrol-XPur in the Korean population.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Polifenóis/administração & dosagem , Adulto , Fármacos Antiobesidade/efeitos adversos , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Polifenóis/efeitos adversos , Adulto Jovem
12.
Sci Rep ; 10(1): 3772, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111933

RESUMO

In this study, ultrasensitive and precise detection of a representative brain hormone, dopamine (DA), was demonstrated using functional conducting polymer nanotubes modified with aptamers. A high-performance aptasensor was composed of interdigitated microelectrodes (IMEs), carboxylated polypyrrole nanotubes (CPNTs) and DA-specific aptamers. The biosensors were constructed by sequential conjugation of CPNTs and aptamer molecules on the IMEs, and the substrate was integrated into a liquid-ion gating system surrounded by pH 7.4 buffer as an electrolyte. To confirm DA exocytosis based on aptasensors, DA sensitivity and selectivity were monitored using liquid-ion gated field-effect transistors (FETs). The minimum detection level (MDL; 100 pM) of the aptasensors was determined, and their MDL was optimized by controlling the diameter of the CPNTs owing to their different capacities for aptamer introduction. The MDL of CPNT aptasensors is sufficient for discriminating between healthy and unhealthy individuals because the total DA concentration in the blood of normal person is generally determined to be ca. 0.5 to 6.2 ng/mL (3.9 to 40.5 nM) by high-performance liquid chromatography (HPLC) (this information was obtained from a guidebook "Evidence-Based Medicine 2018 SCL " which was published by Seoul Clinical Laboratory). The CPNTs with the smaller diameters (CPNT2: ca. 120 nm) showed 100 times higher sensitivity and selectivity than the wider CPNTs (CPNT1: ca. 200 nm). Moreover, the aptasensors based on CPNTs had excellent DA discrimination in the presence of various neurotransmitters. Based on the excellent sensing properties of these aptasensors, the DA levels of exogeneous DA samples that were prepared from PC12 cells by a DA release assay were successfully measured by DA kits, and the aptasensor sensing properties were compared to those of standard DA reagents. Finally, the real-time response values to the various exogeneous DA release levels were similar to those of a standard DA aptasensor. Therefore, CPNT-based aptasensors provide efficient and rapid DA screening for neuron-mediated genetic diseases such as Parkinson's disease.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Dopamina , Exocitose , Nanotubos/química , Animais , Dopamina/análise , Dopamina/metabolismo , Células PC12 , Pirróis/química , Ratos , Transistores Eletrônicos
13.
J Korean Neurosurg Soc ; 63(2): 202-209, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31805759

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the efficacy of the anterior approach following intraoperative reduction under general anesthesia in patients with cervical facet fracture and dislocation. METHODS: Twenty-three patients with single level cervical facet fracture and dislocation who were subjected to the anterior approach alone following immediate intraoperative reduction under general anesthesia from March 2013 to December 2017 were enrolled in this study. Neurological status, clinical outcome, and radiological studies were evaluated preoperatively, postoperatively, and during the follow-up period. RESULTS: The cohort comprised 15 men and eight women with a mean age of 57 years (from 24 to 81). All patients were operated on within the first 8 hours following the injury. After gentle manual reduction or closed reduction with Gardner-Wells traction, under general anesthesia monitored by somatosensory-evoked potentials, all operations were successfully completed using the anterior approach alone except in two patients, who had a risk of over-distraction. In them, a satisfactory gentle manual reduction or closed reduction was not possible, and required open posterior reduction of the locked facets followed by anterior cervical discectomy and fusion. In one patient, screw retropulsion was observed in 1 month after surgery. There were no reduction-related complications or neurological aggravations after surgery. All patients showed evidence of stability at the instrumented level at the final follow-up (mean follow-up, 12 months). CONCLUSION: Anterior approach following intraoperative reduction monitored by somatosensory-evoked potentials under general anesthesia for cervical dislocation and locked facets is a relatively safe and effective alternative when cervical alignment is achieved by intraoperative reduction.

14.
Nat Commun ; 8(1): 903, 2017 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-29026069

RESUMO

MDC1 plays a critical role in the DNA damage response (DDR) by interacting directly with several factors including γ-H2AX. However, the mechanism by which MDC1 is recruited to damaged sites remains elusive. Here, we show that MDC1 interacts with a helix-loop-helix (HLH)-containing protein called inhibitor of DNA-binding 3 (ID3). In response to double-strand breaks (DSBs) in the genome, ATM phosphorylates ID3 at serine 65 within the HLH motif, and this modification allows a direct interaction with MDC1. Moreover, depletion of ID3 results in impaired formation of ionizing radiation (IR)-induced MDC1 foci, suppression of γ-H2AX-bound MDC1, impaired DSB repair, cellular hypersensitivity to IR, and genomic instability. Disruption of the MDC1-ID3 interaction prevents accumulation of MDC1 at sites of DSBs and suppresses DSB repair. Thus, our study uncovers an ID3-dependent mechanism of recruitment of MDC1 to DNA damage sites and suggests that the ID3-MDC1 interaction is crucial for DDR.MDC1 is a key component of the DNA damage response and interacts with several factors such as γ-H2AX. Here the authors show that MDC1 interacts with ID3, facilitating MDC1 recruitment to sites of damage and repair of breaks.


Assuntos
Dano ao DNA , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Bovinos , Proteínas de Ciclo Celular , Quebras de DNA de Cadeia Dupla , Instabilidade Genômica , Células HEK293 , Células HeLa , Sequências Hélice-Alça-Hélice , Histonas/metabolismo , Humanos , Proteínas Inibidoras de Diferenciação , Camundongos , Proteínas de Neoplasias , Radiação Ionizante , Ratos
15.
Biomol Ther (Seoul) ; 25(4): 396-403, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28605833

RESUMO

Under normal, non-stressed conditions, intracellular p53 is continually ubiquitinated by MDM2 and targeted for degradation. However, in response to severe genotoxic stress, p53 protein levels are markedly increased and apoptotic cell death is triggered. Inhibiting the ubiquitination of p53 under conditions where DNA damage has occurred is therefore crucial for preventing the development of cancer, because if cells with severely damaged genomes are not removed from the population, uncontrolled growth can result. However, questions remain about the cellular mechanisms underlying the regulation of p53 stability. In this study, we show that p53-inducible gene 3 (PIG3), which is a transcriptional target of p53, regulates p53 stability. Overexpression of PIG3 stabilized both endogenous and transfected wild-type p53, whereas a knockdown of PIG3 lead to a reduction in both endogenous and UV-induced p53 levels in p53-proficient human cancer cells. Using both in vivo and in vitro ubiquitination assays, we found that PIG3 suppressed both ubiquitination- and MDM2-dependent proteasomal degradation of p53. Notably, we demonstrate that PIG3 interacts directly with MDM2 and promoted MDM2 ubiquitination. Moreover, elimination of endogenous PIG3 in p53-proficient HCT116 cells decreased p53 phosphorylation in response to UV irradiation. These results suggest an important role for PIG3 in regulating intracellular p53 levels through the inhibition of p53 ubiquitination.

16.
Oncotarget ; 8(29): 48204-48221, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28637007

RESUMO

Terminally differentiated cells have a reduced capacity to repair double-stranded breaks (DSB) in DNA, however, the underlying molecular mechanism remains unclear. Here, we show that miR-22 is upregulated during postmitotic differentiation of human breast MCF-7 cells, hematopoietic HL60 and K562 cells. Increased expression of miR-22 in differentiated cells was associated with decreased expression of MDC1, a protein that plays a key role in the response to DSBs. This downregulation of MDC1 was accompanied by reduced DSB repair, impaired recruitment of the protein to the site of DNA damage following IR. Conversely, inhibiting miR-22 enhanced MDC1 protein levels, recovered MDC1 foci, fully rescued DSB repair in terminally differentiated cells. Moreover, MDC1 levels, IR-induced MDC1 foci, and the efficiency of DSB repair were fully rescued by siRNA-mediated knockdown of c-Fos in differentiated cells. These findings indicate that the c-Fos/miR-22/MDC1 axis plays a relevant role in DNA repair in terminally differentiated cells, which may facilitate our understanding of molecular mechanism underlying the downregulating DNA repair in differentiated cells.


Assuntos
Diferenciação Celular/genética , Reparo do DNA , Regulação da Expressão Gênica , MicroRNAs/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Interferência de RNA , Transativadores/genética , Proteínas Adaptadoras de Transdução de Sinal , Ciclo Celular/genética , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Análise por Conglomerados , Quebras de DNA de Cadeia Dupla , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HL-60 , Humanos , Células K562 , Células MCF-7
17.
Prev Nutr Food Sci ; 22(1): 16-20, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28401083

RESUMO

This study investigated the antioxidant activity of functional beverage concentrates containing herbal medicine extracts (FBCH) using various antioxidant assays, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity, and reducing power assay. The total polyphenolic content of FBCH (81.45 mg/100 g) was higher than Ssanghwa tea (SHT, 37.56 mg/100 g). The antioxidant activities of FBCH showed 52.92% DPPH and 55.18% ABTS radical scavenging activities at 100 mg/mL, respectively. FBCH showed significantly higher antioxidant activities compared to the SHT (DPPH, 23.43%; ABTS, 22.21%; reducing power optical density; 0.23, P<0.05). In addition, intracellular reactive oxygen species generation significantly decreased in a concentration-dependent manner following FBCH treatment. These results suggest that the addition of herbal medicine extract contributes to the improved functionality of beverage concentrates.

18.
Korean J Physiol Pharmacol ; 21(2): 267-273, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28280421

RESUMO

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colonderived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.

19.
Biochem Biophys Res Commun ; 482(4): 706-712, 2017 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-27866984

RESUMO

Ribonucleotide reductase small subunit p53R2 is a member of the ribonucleotide reductase family that supplies dNTPs for nuclear and mitochondrial DNA replication and repair. Here, we have identified a mitochondrial thioredoxin reductase 2 (TrxR2) as a novel p53R2-binding protein. We demonstrated a direct interaction between the two, and observed that p53R2 stimulated the enzymatic activity of TrxR in vitro. Moreover, TrxR2 activity was significantly lower in p53R2 knockdown cells, and increased when p53R2 was overexpressed, effects that were independent of p53. Furthermore, p53R2 knockdown suppressed UV-induced TrxR activity. These findings suggest that p53R2 acts as a positive regulator of TrxR2 activity in mitochondria both under normal physiological conditions and during the cellular response to DNA damage.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Regulação Enzimológica da Expressão Gênica , Ribonucleotídeo Redutases/metabolismo , Tiorredoxina Redutase 2/metabolismo , Linhagem Celular Tumoral , Dano ao DNA , Reparo do DNA , DNA Mitocondrial/metabolismo , Vetores Genéticos , Humanos , Mitocôndrias/metabolismo , Plasmídeos/metabolismo , Ligação Proteica , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/metabolismo , Raios Ultravioleta , Regulação para Cima
20.
Polymers (Basel) ; 9(5)2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-30970834

RESUMO

Conducting polymer (CP) hybrids, which combine CPs with heterogeneous species, have shown strong potential as electrical transducers in chemosensors. The charge transport properties of CPs are based on chemical redox reactions and provide various chemo-electrical signal transduction mechanisms. Combining CPs with other functional materials has provided opportunities to tailor their major morphological and physicochemical properties, often resulting in enhanced sensing performance. The hybrids can provide an enlarged effective surface area for enhanced interaction and chemical specificity to target analytes via a new signal transduction mechanism. Here, we review a selection of important CPs, including polyaniline, polypyrrole, polythiophene and their derivatives, to fabricate versatile organic and inorganic hybrid materials and their chemo-electrical sensing performance. We focus on what benefits can be achieved through material hybridization in the sensing application. Moreover, state-of-the-art trends in technologies of CP hybrid sensors are discussed, as are limitations and challenges.

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