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1.
Nano Lett ; 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32543854

RESUMO

The bottom-up synthesis process often allows the growth of metastable phase nanowires instead of the thermodynamically stable phase. Herein, we synthesized Cd3As2 nanowires with a controlled three-dimensional Dirac semimetal phase using a chemical vapor transport method. Three different phases such as the body centered tetragonal (bct), and two metastable primitive tetragonal (P42/nbc and P42/nmc) phases were identified. The conversion between three phases (bct → P42/nbc → P42/nmc) was achieved by increasing the growth temperature. The growth direction is [110] for bct and P42/nbc and [100] for P42/nmc, corresponding to the same crystallographic axis. Field effect transistors and photodetector devices showed the nearly same electrical and photoelectrical properties for three phases. Differential conductance measurement confirms excellent electron mobility (2 × 104 cm2/(V s) at 10 K). Negative photoconductance was first observed, and the photoresponsivity reached 3 × 104 A/W, which is ascribed to the surface defects acting as trap sites for the photogenerated electrons.

2.
Korean J Ophthalmol ; 34(3): 235-241, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32495532

RESUMO

PURPOSE: To investigate the tomographic structural changes in the retinal layers after internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (ERM). METHODS: Sixty-nine eyes treated with vitrectomy and ILM peeling for idiopathic ERM were analyzed. Parafoveal retinal thickness was measured at baseline and 6 months after surgery. RESULTS: Total retinal thickness decreased significantly in the nasal and temporal subfields after surgery (p < 0.001), whereas the inner nuclear layer and outer nuclear layer showed nasal thickening (all, p < 0.001). The postoperative temporal/nasal subfield thickness ratio of each layer was significantly lower than that of fellow eyes. Eyes with larger ILM peeling showed a significantly lower temporal/nasal subfield thickness ratio (p = 0.033) than those with smaller sizes. CONCLUSIONS: The retinal thickness of each layer showed anatomical changes from ILM peeling and ERM removal. Nasal parafoveal thickening and temporal thinning occurred in the inner retinal architecture, which might be affected by ILM peeling size.

3.
Biochimie ; 175: 58-68, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32445654

RESUMO

Hepatocellular carcinoma (HCC) is a major malignancy that stands second in terms of global cancer-related mortality. STAT3 has been described as a latent transcription factor that promotes tumorigenesis. This study was designed to examine the effect of vitexin on STAT3 signaling and important hallmarks of cancer. HCC cells were employed to decipher the impact of vitexin on activation of STAT3 signaling using Western blotting, EMSA, immunocytochemistry, and reporter assay. The combinational apoptotic effects of vitexin with approved anti-cancer drugs was examined by live-dead assay, and its anti-invasive potential was studied using matrigel assay. The results obtained in cell-based assays were verified using in silico analysis. Vitexin effectively inhibited sustained activation of JAK1, JAK2, Src, and STAT3 in HCC cells. Vitexin downregulated DNA binding ability, reduced the nuclear pool of STAT3, and diminished epidermal growth factor (EGF)-driven STAT3 gene expression. Interestingly, treatment with tyrosine phosphatase inhibitor altered the vitexin-induced STAT3 phosphorylation, and the attenuation of STAT3 by vitexin was found to be driven through the upregulation of PTPεC. The combinational studies indicated that vitexin can exhibit substantial apoptotic effects with doxorubicin and sorafenib. It also suppressed the CXCL12-induced cell invasion. The results of cell-based assays are supported by in silico analysis as the vitexin displayed favorable interaction with kinase domain of JAK2 protein. Overall, this study demonstrated that vitexin can act as a potential blocker of the STAT3 signaling cascade and mitigate the survival as well as invasion of HCC cells.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32349463

RESUMO

Background: Fibroma of tendon sheath (FTS) is an uncommon mass that arises from the tendon sheath of extremities, particularly in children. The tumor typically affects adults between ages 20 and 50 years with a predominance in males. To date, growth hormone (GH) treatment is safe for children without risk factors and is accepted worldwide as a treatment for Turner syndrome. Case Description: This article reports the case of a nine-year-old female patient with Turner syndrome and FTS during GH treatment. She had been treated with daily subcutaneous GH to improve growth failure with a mean dose of 0.28 mg/kg/week and the level of insulin-like growth factor 1 (IGF-1) was within the normal range. During the follow-up period, she complained about the mass on her hand and diagnosed as FTS. Conclusion: This report illustrates the clinical impact of Turner syndrome and GH treatments on the occurrence of this tumor through literature reviews. Further studies are needed to highlight the association between FTS and GH treatment, especially in Turner syndrome. Though it is not yet confirmed, it may be worth considering FTS as a possible diagnosis in patients undergoing GH treatment.

5.
Molecules ; 25(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178324

RESUMO

Cancer persists as one of the leading causes of deaths worldwide, contributing to approximately 9.6 million deaths per annum in recent years. Despite the numerous advancements in cancer treatment, there is still abundant scope to mitigate recurrence, adverse side effects and toxicities caused by existing pharmaceutical drugs. To achieve this, many phytochemicals from plants and natural products have been tested against cancer cell lines in vivo and in vitro. Likewise, casticin, a flavonoid extracted from the Vitex species, has been isolated from the leaves and seeds of V. trifolia and V. agnus-castus. Casticin possesses a wide range of therapeutic properties, including analgesic, anti-inflammatory, antiangiogenic, antiasthmatic and antineoplastic activities. Several studies have been conducted on the anticancer effects of casticin against cancers, including breast, bladder, oral, lung, leukemia and hepatocellular carcinomas. The compound inhibits invasion, migration and proliferation and induces apoptosis (casticin-induced, ROS-mediated and mitochondrial-dependent) and cell cycle arrest (G0/G1, G2/M, etc.) through different signaling pathways, namely the PI3K/Akt, NF-κB, STAT3 and FOXO3a/FoxM1 pathways. This review summarizes the chemo-preventive ability of casticin as an antineoplastic agent against several malignancies.

6.
Biosci Rep ; 40(1)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31930392

RESUMO

Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.

7.
Sci Rep ; 10(1): 793, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964980

RESUMO

The most obvious method to observe transplanted islets in the liver is direct biopsy, but the distribution and location of the best biopsy site in the recipient's liver are poorly understood. Islets transplanted into the whole liver of five diabetic cynomolgus monkeys that underwent insulin-independent survival for an extended period of time after allo-islet transplantation were analyzed for characteristics and distribution tendency. The liver was divided into segments (S1-S8), and immunohistochemistry analysis was performed to estimate the diameter, beta cell area, and islet location. Islets were more distributed in S2 depending on tissue size; however, the number of islets per tissue size was high in S1 and S8. Statistical analysis revealed that the characteristics of islets in S1 and S8 were relatively similar to other segments despite various transplanted islet dosages and survival times. In conclusion, S1, which exhibited high islet density and reflected the overall characteristics of transplanted islets, can be considered to be a reasonable candidate for a liver biopsy site in this monkey model. The findings obtained from the five monkey livers with similar anatomical features to human liver can be used as a reference for monitoring transplanted islets after clinical islet transplantation.

8.
Ecotoxicol Environ Saf ; 189: 109933, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757511

RESUMO

Arsenic is a hazardous environmental pollutant widely distributed globally. Arsenic toxicity is well known and it is regulated by many countries in terms of managing water quality and protecting aquatic organisms. Unfortunately, water quality criterion (WQC) to protect aquatic organisms has not been introduced in Korea yet. Thus, it is of great importance and necessity to introduce WQC to protect aquatic organisms from arsenic, as WQC play a significant role in protecting aquatic ecosystems from pollutants. Therefore, the purpose of this study is to derive arsenic water quality criterion for aquatic life in Korea. Arsenic acute toxicity tests were performed with 10 Korean native aquatic species, which belong to 7 different taxonomic groups. Based on the results of acute toxicity test and additional toxicity data from literature, the species sensitivity distribution (SSD) method was used in ecological risk assessment. The arsenic concentration of 95% protection level for aquatic life was 0.229 mg L-1 in this study. An assessment factor 3 and a background concentration 0.0004 mg L-1 were applied to the concentration value in consideration of the uncertainty of the data and the amount of arsenic natural generation. Consequently, the WQC value derived for arsenic was found to be 0.077 mg L-1. These results will serve as reference values to establish water quality criterion for the protection of aquatic life in Korea.


Assuntos
Arsênico/análise , Poluentes Químicos da Água/análise , Qualidade da Água/normas , Animais , Organismos Aquáticos , Ecossistema , República da Coreia , Sensibilidade e Especificidade , Poluentes Químicos da Água/toxicidade
9.
Biomolecules ; 9(12)2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847229

RESUMO

STAT3 is an oncogenic transcription factor that regulates the expression of genes which are involved in malignant transformation. Aberrant activation of STAT3 has been observed in a wide range of human malignancies and its role in negative prognosis is well-documented. In this report, we performed high-throughput virtual screening in search of STAT3 signaling inhibitors using a cheminformatics platform and identified 2-Amino-6-[2-(Cyclopropylmethoxy)-6-Hydroxyphenyl]-4-Piperidin-4-yl Nicotinonitrile (ACHP) as the inhibitor of the STAT3 signaling pathway. The predicted hit was evaluated in non-small cell lung cancer (NSCLC) cell lines for its STAT3 inhibitory activity. In vitro experiments suggested that ACHP decreased the cell viability and inhibited the phosphorylation of STAT3 on Tyr705 of NSCLC cells. In addition, ACHP imparted inhibitory activity on the constitutive activation of upstream protein tyrosine kinases, including JAK1, JAK2, and Src. ACHP decreased the nuclear translocation of STAT3 and downregulated its DNA binding ability. Apoptosis was evidenced by cleavage of caspase-3 and PARP with the subsequent decline in antiapoptotic proteins, including Bcl-2, Bcl-xl, and survivin. Overall, we report that ACHP can act as a potent STAT3 signaling inhibitor in NSCLC cell lines.

10.
Pharmacol Res ; 150: 104504, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678208

RESUMO

Epithelial mesenchymal transition (EMT) refers to a phenomenon through which epithelial cells develop the metastatic and invasive potential, which are closely related to carcinogenesis. Farnesol (FOH) obtained from the oils of diverse plants can exhibit significant therapeutic actions against obesity, diabetes, inflammatory conditions and cancers. Here, we evaluated the potential effects of FOH on growth and metastasis and it was observed that FOH significantly abrogated cell proliferation in lung cancer cells. Moreover, FOH inhibited cell repair movement by wound healing assay and reduced cell adhesion. It suppressed the expression of mesenchymal genes such as fibronectin, vimentin, N-cadherin, twist, and snail, and increased expression of epithelial genes such as occludin and E-cadherin. It also attenuated the migration and invasion through the inhibition of the PI3K/Akt/mTOR signaling pathway. Furthermore, FOH inhibited the tumor growth of xenograft mouse lung cancer model, and modulated the expression of mesenchymal and epithelial markers. The results suggest that FOH may block the PI3K/Akt/mTOR signaling pathway and thus exhibit anti-proliferative and anti-metastatic activity against lung cancer cells.

11.
Int J Pharm ; 572: 118791, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678390

RESUMO

Fluorinated graphene has recently gained much attention for cancer drug delivery, owing to its peculiar properties including high electronegativity difference, magnetic resonance imaging contrast agent, and the photothermal effect. However, the hydrophobic nature of fluorinated graphene greatly hinders its application as a biological material. Herein, a novel green method is reported for synthesis of a pH-sensitive charge-reversal and water-soluble fluorinated graphene oxide, modified with polyethyleneimine anchored to sericin-polypeptide (FPS). This nanocarrier was further loaded with curcumin (Cur), and characterized as a nanocarrier for anti-cancer drug delivery. The synthesized nanocarriers contain two different pH-sensitive amide linkages, which are negatively charged in blood pH (≈7.4) and can prolong circulation times. The amide linkages undergo hydrolysis once they reach the mildly acidic condition (pH≈6.5, corresponding to tumor extracellular matrix), and subsequently once reached the lower acidic condition (pH≈5.5, corresponded to endo/lysosomes microenvironment), the FPS charge can be switched to positive (≈+28 mV), which aids the nuclear release. This nanocarrier was designed to selectively enhance cell internalization and nuclear-targeted delivery of curcumin in HeLa, SkBr3 and PC-3 cancer cells. Moreover, FPS-Cur demonstrated high curcumin loading capacity, prolonged curcumin release and promotion of apoptosis in HeLa, SkBr3 and PC-3 cells. Therefore, with its pH-responsive charge-reversal properties, FPS-Cur would be a promising candidate for chemotherapy of cervical, breast and prostate cancers.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Portadores de Fármacos , Grafite/química , Nanopartículas , Neoplasias/tratamento farmacológico , Sericinas/química , Animais , Antineoplásicos Fitogênicos/química , Curcumina/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Halogenação , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Masculino , Camundongos , Nanotecnologia , Neoplasias/patologia , Células PC-3 , Tecnologia Farmacêutica/métodos
12.
Am J Transl Res ; 11(10): 6422-6432, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737194

RESUMO

Rabbit-antithymocyte globulin (rATG) is commonly used in kidney transplantation (KT) as an induction agent and is also commonly used in non-human primate (NHP) KT models. However, the optimal dose has not been reported. In this study, we evaluated which cumulative dose of rATG was most appropriate for transplantation in NHPs. Cynomolgus monkeys were treated with intravenous 5 mg/kg rATG (Thymoglobulin®, Genzyme Ltd., UK) twice, on days 0 and 2 (a total of 10 mg/kg, n=2), or 4 times, on days 0, 1, 2, and 3 (a total of 20 mg/kg, n=6). In addition, we performed allo-KT in cynomolgus monkeys (n=4) with a cumulative 20 mg/kg dose of rATG with optimized dosing for induction therapy. We further compared immune cells, including naïve, central memory, and effector memory T cells, in reconstituted distributions in human KT patients (n=22). The kinetics of lymphocytes showed a rapid decrease at day 1 that was maintained for 2 weeks in the 20 mg/kg rATG group, while lymphocyte depletion was not maintained for more than 1 week in the 10 mg/kg rATG group. During the early period of rATG treatment in the NHP-KT model, the frequency of total T cells in the 20 mg/kg group showed a pattern of depletion similar with that of KT patients treated with rATG (1.5 mg/kg, 3 days). However, the pattern of reconstituted T cell subpopulations was different, as the number of effector memory cells rebounded in the NHP-KT model. These data indicate that lymphocyte-depletion induced by rATG was influenced by cumulative dose, and that an rATG dose of 20 mg/kg is suitable for induction therapy in renal transplantation in cynomolgus monkeys compared to human KT.

13.
Am J Transl Res ; 11(10): 6444-6453, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737196

RESUMO

Bone marrow preconditioning using cyclophosphamide (CP) is generally used for bone marrow transplantation (BMT). However, because of CP's hepatotoxicity and nephrotoxicity, additional fludarabine (FDR) administration and a reduced dose of CP are used for reduced-intensity preconditioning. Recently, preclinical studies using non-human primates (NHPs) were performed to induce immune tolerance after solid organ transplantation by conducting BMT simultaneously. However, dose optimization of CP and FDR for BMT preconditioning in cynomolgus monkeys has not been conducted. Therefore, the objective of this study was to evaluate the efficacy and tolerability of induction protocols using different doses of CP and FDR. Our results showed that relatively low-dose CP (30 mg/kg×2) combined with additional high-dose FDR (60 mg/m2×4) was associated with sufficient suppression in periphery as well as in bone marrow compared with high-dose CP (60 mg/kg×2) combined with low-dose FDR (30 mg/m2×4) and did not show hepatic or renal toxicity. CD34+ stem cells were also well suppressed with both doses. Therefore, we concluded that the combination of 60 mg/kg of CP with 240 mg/m2 of FDR can be used effectively and safely for non-myeloablative preconditioning for BMT in cynomolgus monkeys.

14.
Biomolecules ; 9(10)2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575007

RESUMO

STAT3 is a latent transcription factor that plays a vital role in the transmission of extracellular signal from receptors to the nucleus. It has been regarded as a master transcription factor due to its role in the regulation of a broad spectrum of genes, which can contribute to oncogenesis. Persistent activation of STAT3 and deregulation of its signaling has been observed in various human cancers including head and neck squamous cell carcinoma (HNSCC). In the present work, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells. The data from the cell-based experiments suggested that BT-induced cytotoxicity and abrogated the activation of STAT3 and that of upstream kinases such as JAK1, JAK2, and Src. It reduced the levels of nuclear STAT3 and its DNA binding ability. BT treatment increased annexin-V-positive cells, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells. Taken together, brusatol can function as a promising inhibitor targeting STAT3 signaling pathway in HNSCC.

15.
PLoS One ; 14(9): e0221322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487292

RESUMO

BACKGROUND: In Korea, several household humidifier disinfectants (HDs) were clinically confirmed to cause HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) phosphate is the main ingredient of the HDs found to be associated with lung disease. However, the association of HDs with other interstitial lung disease including idiopathic interstitial pneumonia (IIP) is not clear. We examined the relationship between HD exposure and IIP in a family-based study. METHODS: This case-control study included 244 IIP cases and 244 family controls who lived with the IIP patients. The IIP cases were divided into two groups, HDLI and other IIP, and were matched to family controls based on age and gender. Information on exposure to HDs was obtained from a structured questionnaire and field investigations. Conditional logistic regression was used to estimate odds ratio (ORs) and their corresponding 95% confidence interval (CI), investigating the association of HD-related exposure characteristics with IIP risk. RESULTS: The risks of IIP increased two-fold or more in the highest compared with the lowest quartile of several HD use characteristics, including average total use hours per day, cumulative sleep hours, use of HD during sleep, and cumulative exposure level. In analyses separated by HDLI and other IIP, the risks of HDLI were associated with airborne HD concentrations (adjusted OR = 3.01, 95% CI = 1.34-6.76; Q4 versus Q1) and cumulative exposure level (adjusted OR = 3.57, 95% CI = 1.59-8.01; Q4 versus Q1), but this relationship was not significant in the patients with other IIP. In comparison between HDLI and other IIP, the odds ratios of average total use hours, cumulative use hours, and cumulative sleeps hours was higher for other IIP. CONCLUSION: The use of household HDs is associated not only with HDLI but also with other IIP.


Assuntos
Desinfetantes/efeitos adversos , Umidificadores/estatística & dados numéricos , Pneumonias Intersticiais Idiopáticas/etiologia , Exposição por Inalação/efeitos adversos , Adulto , Estudos de Casos e Controles , Características da Família , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/epidemiologia , Pneumonias Intersticiais Idiopáticas/patologia , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
16.
Biomolecules ; 9(7)2019 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-31284669

RESUMO

Here, we determined the anti-neoplastic actions of formononetin (FT) against multiple myeloma (MM) and elucidated its possible mode of action. It was observed that FT enhanced the apoptosis caused by bortezomib (Bor) and mitigated proliferation in MM cells, and these events are regulated by nuclear factor-κB (NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, and activator protein-1 (AP-1) activation. We further noted that FT treatment reduced the levels of diverse tumorigenic proteins involved in myeloma progression and survival. Interestingly, we observed that FT also blocked persistent NF-κB, PI3K/AKT, and AP-1 activation in myeloma cells. FT suppressed the activation of these oncogenic cascades by affecting a number of signaling molecules involved in their cellular regulation. In addition, FT augmented tumor growth-inhibitory potential of Bor in MM preclinical mouse model. Thus, FT can be employed with proteasomal inhibitors for myeloma therapy by regulating the activation of diverse oncogenic transcription factors involved in myeloma growth.


Assuntos
Antineoplásicos/farmacologia , Bortezomib/farmacologia , Isoflavonas/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Knockout , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Fator de Transcrição AP-1/antagonistas & inibidores , Fator de Transcrição AP-1/metabolismo
17.
PLoS One ; 14(6): e0218571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31247046

RESUMO

This paper reports an outdoor-use polymerase chain reaction (PCR) technology in which stability of resistance temperature detectors (RTDs) is remarkably improved. A thin-film RTD made of non-annealed Pt shows accuracy degradation because the resistance of the RTD tends to decrease during the PCR operation. Thus, the annealing process is applied to the Pt RTD to improve the stability, which is a prerequisite to the accurate measurement of the absolute temperature. Both heaters and the RTD are fabricated on a thin quartz substrate whose melting temperature is high enough for annealing. The performances in the PCR time and power consumption are enhanced by reducing the size of the heater chips with no degradation in the temperature uniformity. A spring-loaded electrode is employed to simplify the procedure of electrical connection to the thermal controller and loading/unloading of the PCR chip. The contact area of the electrical connection is so small that the conductive thermal resistance increases; thereby small heat dissipation can be exploited for low-power operation. The stability of the RTD is experimentally confirmed in terms of resistance variation over repeated PCR operations (four times). The least variation of 0.005%, which corresponds to a negligible temperature variation of 0.038 °C for the PCR, is achieved from the RTD annealed for 5 min at 450 °C. The gel-electrophoresis result indicates that the PCR performance of the proposed system using a film-type PCR chip is comparable to that of a conventional system using a vial tube despite its low power consumption.


Assuntos
Reação em Cadeia da Polimerase/instrumentação , Simulação por Computador , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Impedância Elétrica , Fontes de Energia Elétrica , Eletroforese , Desenho de Equipamento , Escherichia coli/genética , Humanos , Platina , Reação em Cadeia da Polimerase/estatística & dados numéricos , Temperatura
18.
Pharm Biol ; 57(1): 392-402, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31188689

RESUMO

Context: Citrus unshiu Markovich (Rutaceae) peel is known to contain high concentrations of flavonoids and exerts pharmacological effects on antioxidant, anti-inflammation, allergies, diabetes and viral infections. Objective: Very little is known about potential activity of fermented dried Citrus unshiu peel extracts (FCU) using Bacillus subtilis, as well as its mechanism of action. We investigated the effects of FCU on the anti-inflammatory activities in murine macrophages and moisturizing effects in human keratinocytes. Materials and methods: We isolated the Bacillus subtilis from Cheonggukjang and FCU using these Bacillus subtilis to prepare samples. The cells were pre-treated with various extracts for 2 h and then induced with LPS for 22 h. We determined the NO assay, TNF-α, IL-6 and PGE2 in RAW 264.7 ells. The expression of SPT and Filaggrin by FCU treatment was measured in HaCaT cells. Result: We found that two types of FCU highly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells (21.9 and 15.4% reduction). FCU inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNAs in a concentration-dependent manner. TNF-α (59 and 30.9% reduction), IL-6 (39.1 and 65.6% reduction), and PGE2 secretion (78.6 and 82.5% reduction) were suppressed by FCU in LPS-stimulated macrophages. Furthermore, FCU can induce the production of hyaluronic acid (38 and 38.9% induction) and expression of Filaggrin and SPT in HaCaT keratinocyte cells. Discussion and conclusion: FCU potentially inhibits inflammation, improves skin moisturizing efficacy, and it may be a therapeutic candidate for the treatment of inflammation and dry skin.


Assuntos
Anti-Inflamatórios/farmacologia , Citrus/química , Queratinócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Bacillus subtilis/metabolismo , Linhagem Celular , Citrus/metabolismo , Citrus/microbiologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Humanos , Fatores Imunológicos/farmacologia , Queratinócitos/metabolismo , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Creme para a Pele/farmacologia
19.
Nutrients ; 11(5)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137609

RESUMO

Obesity is one of major health challenges in the industrial world. Although rice hull has been reported to show various bioactivities, no studies have evaluated its anti-obesity effect. We hope to demonstrate the anti-obesity effect of rice hull extract (RHE) and the underlying mechanism in high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Serum lipid profiles were determined by enzymatic methods. Histological analysis of liver and epididymis fat tissues was carried out with hematoxylin and eosin stain. The mRNA expression of adipogenic markers was analyzed with qRT-PCR and western blotting. Oral administration of RHE reduced body weight gain and fat accumulation in HFD-fed mice. RHE also reduced lipid accumulation by inhibiting the mRNA expression of adipogenic-related genes in HFD-fed obese mice and differentiated preadipocytes. The downregulation of adipogenesis by RHE was mediated through the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, RHE induced the phosphorylation of c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinases (ERK) in liver and epididymis adipose tissues of HFD-fed obese mice. Taken together, these findings indicate that RHE could inhibit the differentiation of adipose cell and prevent HFD-induced obesity, suggesting its potential in the prevention of obesity and metabolic syndrome and related-disorders.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Obesidade/prevenção & controle , Oryza , Extratos Vegetais/farmacologia , Sementes , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/genética , Animais , Fármacos Antiobesidade/isolamento & purificação , Modelos Animais de Doenças , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Obesidade/sangue , Obesidade/patologia , Obesidade/fisiopatologia , Oryza/química , Fosforilação , Extratos Vegetais/isolamento & purificação , Sementes/química , Transdução de Sinais , Ganho de Peso/efeitos dos fármacos
20.
Biomolecules ; 9(5)2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058868

RESUMO

Aberrant activation of signal transducer and activator of transcription 3 (STAT3) has been documented in various malignancies including triple-negative breast cancers (TNBCs). The STAT3 transcription factor can regulate the different important hallmarks of tumor cells, and thus, targeting it can be a potential strategy for treating TNBC, for which only limited therapeutic options are available. In this study, we analyzed the possible effect of (-)-galiellalactone and its novel analogues, SG-1709 and SG-1721, and determined whether these agents exerted their antineoplastic effects by suppressing the STAT3 signaling pathway in TNBC cells. The two analogues, SG-1709 and SG-1721, inhibited both constitutive as well as inducible STAT3 phosphorylation at tyrosine 705 more effectively than (-)-galiellalactone, which indicates that the analogues are more potent STAT3 blockers. Moreover, SG-1721 not only inhibited nuclear translocation and DNA binding of STAT3 but also induced apoptosis, and decreased expression of diverse oncogenic proteins. Interestingly, SG-1721 also exhibited an enhanced apoptotic effect when combined with radiotherapy. Furthermore, in vivo administration of SG-1721 significantly attenuated breast xenograft tumor growth via decreasing levels of p-STAT3. Therefore, SG-1721 may be a promising candidate for further application as a pharmacological agent that can target STAT3 protein in treating TNBC.


Assuntos
Apoptose/efeitos dos fármacos , Lactonas/farmacologia , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Animais , Biomarcadores Tumorais/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Janus Quinases/metabolismo , Lactonas/química , Camundongos Nus , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/radioterapia
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