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In this paper; the surface plasmon resonance (SPR) sensor with a porous silica film was studied. The effect of the thickness and porosity of the porous silica film on the performance of the sensor was analyzed. The results indicated that the figure of merit (FOM) of an SPR sensor can be enhanced by using a porous silica film with a low-refractive-index. Particularly; the FOM of an SPR sensor with 40 nm thick 90% porosity porous silica film; whose refractive index is 1.04 was improved by 311% when compared with that of a traditional SPR sensor. Furthermore; it was found that the decrease in the refractive index or the increase in the thickness of the low-refractive-index porous silica film can enlarge the FOM enhancement. It is believed that the proposed SPR sensor with a low-refractive-index porous silica film will be helpful for high-performance SPR sensors development.
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The antitumor activity of shikonin derivatives is largely dependent on the generation of superoxide radicals and the alkylation activity of their naphthoquinone moiety. However, our recent study showed that 1,4-dioxime-5,8-dimethoxynaphthalene (DMAKO-05), a novel shikonin derivative, displayed more potential antitumor activity and less toxicity compared to fluorouracil (5-FU) both in vitro and in vivo, even though the hydroxyl and carbonyl groups of its naphthoquinone structure were shielded. To understand the underlying mechanisms, we investigated the metabolism of DMAKO-05 in rat liver microsomes. The kinetic analysis indicated that DMAKO-05 underwent a biphasic metabolism in rat liver microsomes. The inhibition experiments showed that CYP1A and CYP3A were the major enzymes in the metabolism of DMAKO-05, along with partial contribution from CYP2A. In addition, the structures of eight DMAKO-05 metabolites, which were characterized by accurate mass and MS/MS fragmentograms, implied that DMAKO-05 was mainly metabolized through the oxygenation of its naphthoquinone nucleus and the hydrolysis of its side chain, instead of the oxidation of hydroxyimine to ketone. Therefore, DMAKO-05 should not be considered as a traditional naphthoquinone prodrug.
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Antineoplásicos/metabolismo , Microssomos Hepáticos/metabolismo , Naftoquinonas/metabolismo , Animais , Linhagem Celular Tumoral , Fluoruracila/metabolismo , Células HCT116 , Humanos , Cinética , Masculino , Pró-Fármacos/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
To improve the utilization efficiency of nutrients and water and determine the best drip irrigation frequency for long-season tomato cultivation in solar greenhouses, we cultivated tomato grafted seedlings in soil using an integrated water and fertilizer technology: drip irrigation under mulch. Seedlings drip-irrigated with balanced fertilizer (containing 20% N, 20% P2O5, and 20% K2O) and high-K fertilizer (containing 17% N, 8% P2O5, and 30% K2O) once every 12 days were set as control (CK) and that with water once every 12 days as CK1, while other seedling groups, drip-irrigated with a nutrient solution of Yamazaki (1978) formula for tomato, were set as treatments (T1-T4). There were four drip-irrigation frequencies, i.e., once every 2 days (T1), 4 days (T2), 6 days (T3), or 12 days (T4), who received the same total amounts of fertilizer and water over the 12 experimental days. The results showed that, with the decreases of drip irrigation frequency, tomato yield, the accumulation of N, P and K in plant dry matter, the fertilizer partial productivity, and the nutrient utilization rate first increased and then decreased, peaking at the T2 treatment. Compared with CK, under the T2 treatment, plant dry matter accumulation and the accumulation of N, P and K increased by 4.9%, 8.0%, 8.0%, 16.8%, the partial productivity of fertilizer and the utilization efficiency of water increased by 142.8% and 12.2%, the use efficiency of N, P and K was better than CK by 241.4%, 466.6% and 235.9%, respectively, and the tomato yield increased by 12.2%. Under the experimental conditions, drip irrigation with the Yamazaki nutrient solution at a frequency of 4 days could increase the tomato yield, as well as the use efficiency of nutrients and water. Under long-season cultivation, these trends would result in considerable saving of water and fertilizer. Overall, our findings provided a basis for improving the scientific management of water and fertilizers under long-season tomato cultivation in protected facilities.
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Solanum lycopersicum , Fertilizantes/análise , Estações do Ano , Nitrogênio/análise , Solo , Água , Nutrientes , Irrigação Agrícola/métodosRESUMO
BACKGROUND: Colorectal cancer remains a considerable challenge in healthcare nowadays. Approximately 60%-80% of colorectal cancer is caused by intestinal polyps, and resection of intestinal polyps has been proved to reduce the incidence of colorectal cancer. The vast majority of intestinal polyps can be found during colonoscopy and removed endoscopically. Therefore, more attention has been paid to the development of endoscopic resection of intestinal polyps. In this study, we compared the efficacy and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP). AIM: To investigate the efficacy and safety of CSP and HSP for colorectal polyps. METHODS: Between January and December 2020, 301 patients with colorectal polyps 4-9 mm in diameter were treated with endoscopic therapy in our hospital, and were divided into the CSP group (n = 154) and HSP group (n = 147). The operating time, incidence of bleeding and perforation, use of titanium clips, and complete resection rate were compared between the two groups. RESULTS: We included 249 patients (301 polyps). No differences in gender, age, and polyp size, location, shape and type were observed between the CSP and HSP groups, and the resection rates in these two groups were 93.4% and 94.5%, respectively, with no significant difference. The use of titanium clips was 15.6% and 95.9%, the operating time was 3.2 ± 0.5 min and 5.6 ± 0.8 min, the delayed bleeding rate was 0% and 2.0%, and delayed perforation was 0% and 0.7%, in the CSP and HSP groups, respectively. CONCLUSION: For sessile colorectal polyps < 10 mm, CSP had the same resection rate of impaired tissue integrity as traditional HSP had. The rate of complications was lower in the CSP group. CSP is a safe and effective method for polypectomy.
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BACKGROUND: Benign esophageal tumors are rare accounting for < 1% of esophageal tumors; two-thirds of which are leiomyomas. Esophageal leiomyoma is a benign tumor derived from mesenchymal tissue that is completely muscularly differentiated. Most esophageal leiomyomas are < 5 cm. Esophageal leiomyomas > 5 cm are rare. We describe a case of a large esophageal leiomyoma involving the cardia and diaphragm. CASE SUMMARY: A 35-year-old woman presented to the doctor because of a choking sensation after eating. Physical examination showed no positive signs. Gastroscopy indicated an uplifted change in the cardia. Enhanced computed tomography revealed space-occupying lesions in the lower part of the esophagus and cardia, which were likely to be malignant. Positron emission tomography-computed tomography showed increased metabolism of soft tissue masses in the lower esophagus and near the cardia. Malignant lesions were considered, and mesenchymal tumors were not excluded. Endoscopic ultrasonography was performed to examine a hypoechoic mass in the lower esophagus, which was unclear from the esophageal wall. Clinical evaluation suggested diagnosis of esophageal and cardiac stromal tumors. Finally, histological specimens obtained by endoscopic ultrasonography- fine needle aspiration suggested leiomyoma. The patient underwent laparoscopic local resection of the tumor. The postoperative pathological diagnosis was leiomyoma. CONCLUSION: Endoscopic ultrasonography-fine needle aspiration is necessary for the diagnosis of gastrointestinal leiomyomas. It provides a strong basis for diagnosis of gastrointestinal tumors of unknown nature and origin.
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Objective: To investigate the effects of transcranial direct current stimulation (tDCS) on the disturbance of brain network dysfunction after sleep deprivation (SD). Methods: The experimental design of self-control was used in the study. All 16 subjects received 2 times of 24 h SD with an interval of 3 weeks. After the first normal sleep, 24 h SD and transcranial electrical stimulation (true or false stimulation) intervention (the current magnitude of true and false stimulation was 1 mA, and the action time was 20 min and 2 s, respectively. The intervention experiment lasted for 20 min. ) and the resting magnetic resonance imaging data were collected after the second transcranial electrical stimulation (sham or true stimulation). The resting fMRI data were collected as baseline before SD, the bilateral posterior cingulate cortex in the default mode network was selected as the seed point, and the functional connectivity between the seed points and the whole brain was calculated. Results: Compared with the rest wakefulness, the functional connectivity among bilateral posterior cingulate cortex, bilateral thalamus and hippocampus was increased (Pï¼0. 01), but connected with the right precuneus, bilateral insula was decreased after 24 h SD (Pï¼0. 01). Compared with the sham tDCS group, the functional connectivity between left posterior cingulate cortex seed point and right precuneus of tDCS group was increased (Pï¼0. 01); but decreased with the bilateral thalamus, insula and right cerebral cortex (Pï¼0. 01). There was a decrease in the functional connectivity among the right posterior cingulate cortex and the bilateral thalamus, right insula, and cerebral cortex(Pï¼0. 01). Conclusion: 24-hours sleep deprivation can cause functional connection disorder of bilateral posterior cingulate gyrus, and transcranial electrical stimulation can improve the functional connection disorder after sleep deprivation to some extent.
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Giro do Cíngulo/fisiopatologia , Privação do Sono , Estimulação Transcraniana por Corrente Contínua , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Multi-drug resistance (MDR) to anticancer drugs is the primary impediment to successful treatment of cancer. Hunting for new compounds with potent anti-MDR activity is an effectual approach to conquer cancer drug resistance. In this work, 33 new sulfur-containing 1,4-naphthoquinone oxime derivatives were prepared and investigated for their cytotoxicity against a panel of tumor cell lines and fibroblast normal cell line. Cell-based assay showed that most of target compounds displayed more potent cytotoxic potency than positive controls. Meanwhile, all of compounds were non-toxic to normal cells. More importantly, the cytotoxic activity of these oxime derivatives toward drug-resistant cancer cell lines was found to be much stronger than that toward drug-susceptible cell lines (anti-drug resistance coefficient (ADRC)â¯>â¯1). Of these, compound 12â¯m was identified as the most effective molecule with IC50 values in the range of 0.29⯱â¯0.01 to 1.33⯱â¯0.05⯵M toward MDR sublines. Further mechanism studies demonstrated that 12â¯m could inhibit colony formation, cause G1 phase arrest and promote cell apoptosis mediated by augmenting Bax/Bcl-2 ratio of Bel7402/5-FU cells. Our findings provide promising start points for development of sulfur-containing 1,4-naphthoquinone oxime derivatives as potential anti-MDR agents.
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Antineoplásicos/síntese química , Resistencia a Medicamentos Antineoplásicos , Naftoquinonas/farmacologia , Oximas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Naftoquinonas/química , Oximas/química , Relação Estrutura-Atividade , EnxofreRESUMO
Shikonin, alkannin and their derivatives, the main ingredient of Lithospermum erythrorhizon and Arnebia euchroma (Royle) Johnst native to Inner Mongolian and Northwest of China respectively, hold promising potentials for antitumor effects via multiple-target mechanisms. This review will emphasize the importance of their antitumor activity in apoptosis, necroptosis and immunogenic cell death, and expound the relationship of their antitumor activity and naphthoquinone scaffold that could generate ROS and alkylating agent. Meanwhile, the antitumor mechanisms of naturally-occurring shikonin, alkannin and their derivatives, which were divided into the direct interaction involved in alkylating agent, covalently binding the DNA and protein, as well as the indirect interaction mediated by ROS, nonspecifically influencing the mitochondria or multiple signal pathways, will be systematically summarized and discussed.
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Antineoplásicos Fitogênicos/farmacologia , Naftoquinonas/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lithospermum/química , Naftoquinonas/química , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
As a continuation of our research on developing potent and potentially safe antineoplastic agents, a set of forty five sulfur-containing shikonin oxime derivatives were synthesized and evaluated for their in vitro cytotoxic activity against human colon cancer (HCT-15), gastric carcinoma (MGC-803), liver (Bel7402), breast (MCF-7) cancer cells and human skin fibroblast (HSF) cells. All the synthesized compounds exhibited potent cytotoxic activity selectively towards HCT-15 cells and did not display apparent toxicity to the normal HSF cells, some of which were more or comparatively effective to the parent compound against HCT-15, MGC-803 and Bel7402 cells. The most active agent 9m displayed high potency against human cancer cells with IC50 ranging from 0.27 ± 0.02 to 9.23 ± 0.12 µM. The structure-activity relationships (SARs) studies suggested that the nature of substituent group in the side chain is important for antitumor potency in vitro. Additionally, nitric oxide release studies revealed that the amount of nitric oxide generated from these oxime derivatives was relatively low. Furthermore, cellular mechanism investigations indicated that compound 9m could arrest cell cycle at G1 phase and induce a strong apoptotic response in HCT-15 cells. Moreover, western blot studies revealed that compound 9m induced apoptosis through the down-regulation of Bcl-2 and up-regulation of Bax, caspase 3 and 9. For all these reasons, compound 9m hold promising potential as antineoplastic agent.
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Antineoplásicos/farmacologia , Naftoquinonas/farmacologia , Oximas/farmacologia , Enxofre/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Oximas/síntese química , Oximas/química , Relação Estrutura-Atividade , Enxofre/química , Células Tumorais CultivadasRESUMO
AIM: To evaluate the numbers of different subsets of monocytes and their associations with the values of clinical measures in mild acute pancreatitis (MAP) patients. METHODS: The study included one group of 13 healthy controls and another group of 24 patients with new-onset MAP. The numbers of different subsets of monocytes were examined in these two groups of subjects by flow cytometry. The concentrations of plasma interleukin (IL)-10 and IL-12 were determined by cytometric bead array. The acute physiology and chronic health evaluation (APACHE) II scores of individual patients were evaluated, and the levels of plasma C-reactive protein (CRP) as well as the activities of amylase and lipase were measured. RESULTS: In comparison with that in the controls, significantly increased numbers of CD14+CD163-, CD14+CD163-MAC387+ M1 monocytes, but significantly reduced numbers of CD14+CD163+IL-10+ M2 monocytes were detected in the MAP patients (P < 0.01 or P < 0.05). Furthermore, significantly higher levels of plasma IL-10 and IL-12 were observed in the MAP patients (P < 0.01 for all). More importantly, the levels of plasma CRP were positively correlated with the numbers of CD14+CD163- (R = 0.5009, P = 0.0127) and CD14+CD163-MAC387+ (R = 0.5079, P = 0.0113) M1 monocytes and CD14+CD163+CD115+ M2 monocytes (R = 0.4565, P = 0.0249) in the patients. The APACHE II scores correlated with the numbers of CD14+CD163+CD115+ (R = 0.4581, P = 0.0244) monocytes and the levels of plasma IL-10 (R = 0.4178, P = 0.0422) in the MAP patients. However, there was no significant association among other measures tested in this population. CONCLUSION: Increased numbers of CD14+CD163- and CD14+ CD163-MAC387+ monocytes may contribute to the pathogenesis of MAP, and increased numbers of CD14+CD163+CD115+ monocytes may be a biomarker for evaluating the severity of MAP.
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Monócitos/citologia , Pancreatite/sangue , Doença Aguda , Adulto , Amilases/sangue , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Inflamação , Interleucina-10/sangue , Interleucina-12/sangue , Lipase/sangue , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Receptor de Fator Estimulador de Colônias de Macrófagos/sangue , Receptores de Superfície Celular/sangueRESUMO
To minimize the cytotoxicity of shikonin and alkannin that arises through the generation of reactive oxygen species (ROS) and alkylation of the naphthazarin ring, two series of novel core-scaffold-modified shikonin and alkannin derivatives were designed. These derivatives, which differ in their configurational and positional isomerism (R-, S-, and 2- and 6-isomers) were synthesized in high enantiomeric excess (>99 % ee). The selectivity of the dimethylated derivatives was significantly higher than the parent shikonin in vitro, but some side effects were still observed in vivo. Surprisingly, the dimethylated diacetyl derivatives with poor anticancer activity in vitro showed tumor-inhibiting effects similar to paclitaxel without any toxicity in vivo. The anticancer activity of these derivatives is in agreement with their low ROS generation and alkylating capacity, emphasizing their potential as prodrugs. This strategy provides means to address the nonspecific cytotoxicity of naphthazarin analogues toward normal cells.