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Nanoparticle (NP)-coated (immobilized) bacteria are an effective method for treating environmental pollution due to their multifarious benefits. This review collates a vast amount of existing literature on organic pollution treatment using NP-coated bacteria. We discuss the features of bacteria, NPs, and decoration techniques of NP-bacteria assemblies, with special attention given to the surface modification of NPs and connection mechanisms between NPs and cells. Furthermore, the performance of NP-coated bacteria was examined. We summarize the factors that affect bioremediation efficiency using coated bacteria, including pH, temperature, and agitation, and the possible mechanisms involving them are proposed. From future perspectives, suitable surface modification of NPs and wide application in real practice will make the NP-coated bacterial technology a viable treatment strategy.
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Nanopartículas , Biodegradación Ambiental , BacteriasRESUMEN
The influence of the combined application of chemical fertilizer with green manure on the stabilization of organic carbon (C) was explored in the organo-mineral complexes of paddy soil. The organo-mineral complexes were isolated from paddy soil treated with no fertilizer, chemical fertilizer alone, and chemical fertilizer combined with increasing amounts of Chinese milk vetch (CMV). The stability (reflected by mineralizable carbon proportion), the content and chemical composition of organic C, the Fe/Al oxides and their associated organic C in the organo-mineral complexes were investigated. The application of chemical fertilizer in combination with CMV significantly improved the stability of organic C in the organo-mineral complexes. The combined application of chemical fertilizer with CMV slightly decreased the proportion of O-alkyl C (easily decomposed) yet somewhat increased the proportions of carbonyl C and aromatic C (difficultly decomposed) and aromaticity index in the organo-mineral complexes. The treatments of chemical fertilizer combined with CMV showed more Fe oxides and Fe/Al-associated organic C and higher proportion of Fe/Al-associated organic C in the total organic C of the organo-mineral complexes. The mineralizable carbon proportion displayed significantly negative correlations with carbonyl C and Fe/Al oxide-associated organic C in the organo-mineral complexes. The Fe/Al oxides were likely to be preferentially bound with the aromatic C and carbonyl C in the organo-mineral complexes. Overall, the combined application of chemical fertilizer with CMV facilitated the association of difficultly decomposed carbon and Fe/Al oxides, which significantly improved the stabilization of organic C in the organo-mineral complexes of paddy soil.
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Infecciones por Citomegalovirus , Suelo , Humanos , Suelo/química , Carbono/química , Estiércol , Fertilizantes , Minerales/química , Óxidos , AgriculturaRESUMEN
Acer miaotaiense P. C. Tsoong is a rare and endangered tree endemic to the Qinling Mountains of China and is listed as a national third-class protected plant. In this study, we sequenced the complete mitochondrial genome of Acer miaotaiense using the Illumina Novaseq 6000 and Nanopore platforms. The total mitochondrial genome length is 819,227 bp and has 69 genes, including 41 protein-coding, 25 tRNA, and 3 rRNA genes. The genome nucleotide composition was asymmetric, with an overall G + C content of 45.7%. Phylogenetic analysis indicated that Acer miaotaiense is closely related to the congeneric Acer yangbiense.
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The proinflammatory property of cisplatin is potentially destructive and contributes to the pathogenesis of acute kidney injury (AKI). The role and upstream regulatory mechanism of histone acetyltransferase 1 (HAT1) in acute kidney inflammation are still unknown. We performed RNA sequencing to filter differentially expressed microRNAs (miRNAs) in the kidney tissue of mice with AKI induced by cisplatin and ischemia-reperfusion. Here, we found that miR-486-5p was upregulated and that the expression of HAT1 was reduced in AKI mouse models and injured human renal proximal tubular epithelial cell (HK-2) model induced by cisplatin. miR-486-5p is implicated in cisplatin-induced kidney damage in vivo. Bioinformatics analysis predicted a potential binding site between miR-486-5p and HAT1. The Luciferase reporter assay and Western blot confirmed that miR-486-5p directly targeted the 3'-untranslated region of HAT1 mRNA and inhibited its expression in the cytoplasm of HK-2 cells. In the in vitro study, inhibiting miR-486-5p reduced apoptosis, and the expression of proinflammatory mediators was induced by cisplatin in HK-2 cells. Simultaneously, the downregulation of miR-486-5p inhibited the activation of the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB). We further found that HAT1 could inhibit apoptosis and the activation of cisplatin on the TLR4/NF-κB pathway and that the upregulation of miR-486-5p reversed this effect. Therefore, the upregulation of miR-486-5p targeting HAT1 promoted the cisplatin-induced apoptosis and acute inflammation response of renal tubular epithelial cells by activating the TLR4/NF-κB pathway, providing a new basis to highlight the potential intervention of regulating the miR-486-5p/HAT1 axis.
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Lesión Renal Aguda , MicroARNs , Regiones no Traducidas 3' , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Animales , Apoptosis , Cisplatino/efectos adversos , Células Epiteliales/metabolismo , Histona Acetiltransferasas/genética , Inflamación/inducido químicamente , Inflamación/genética , Ratones , MicroARNs/metabolismo , FN-kappa B/metabolismo , Receptor Toll-Like 4/genéticaRESUMEN
BACKGROUND: Colorectal mucinous adenocarcinoma is a distinct subtype of colorectal adenocarcinoma that is not sensitive to chemotherapy and radiotherapy, and its prognosis is worse than that of nonmucinous adenocarcinoma. Early diagnosis and aggressive surgical treatment may be the key to improving the prognosis of patients. Ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess caused by non-intestinal perforation has never been reported. Moreover, since the lumen of the ascending colon is large, and early stage ascending colon cancer lacks typical clinical manifestations, the diagnosis may be delayed easily. We herein report three cases of delayed diagnosis of colorectal mucinous adenocarcinoma. CASE SUMMARY: We present three patients (two females and one male) with mucinous ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess (the right area of the lumbar spine, right groin, and lower right abdomen) caused by non-intestinal perforation. At the initial clinical visit, the common causes of those abscesses, including spinal tuberculosis and urinary tract infection, were excluded. The treatment of the abscess was through an incision and drainage. However, the source of the abscess was not made clear, which led to an abscess recurrence and a delayed diagnosis of colorectal mucinous adenocarcinoma. After the patients were referred to our hospital, a definitive diagnosis of ascending colon mucinous adenocarcinoma was made with the help of tumor markers and colonoscopic findings. Because of the delayed diagnosis of the disease, two patients (case 1 and case 2) missed the chance of surgery due to disease progression and died in a short follow-up period. Only case 3 underwent radical surgery for the tumor in the right colon and partial abdominal wall resection and achieved a better prognosis. CONCLUSION: Abscesses in the right area of the lumbar spine, right groin, or right lower quadrant caused by non-intestinal perforation as the primary clinical manifestation of ascending colon mucinous adenocarcinoma are extremely rare. Mucinous adenocarcinoma of the ascending colon may be one of the causes of such abscesses. Performing colonoscopy as soon as possible is of great significance in the diagnosis and treatment of the disease.
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We carried out a 3-year field experiment with three treatments: 1) no fertilizer application (CK), 2) chemical fertilizer application (F), and 3) combined organic and chemical fertilizer (FM) in which the total nitrogen inputs were equal with F (organic fertilizer applied in the early rice season). We evaluated the variations of crop yield, CH4 and N2O emission, and soil nutrient. The results showed that fertilizer application could increase rice yield in both early and late rice seasons. Compared with F treatment, FM treatment increased rice yield by 5.6% and 7.2% for early and late rice, respectively. The enhancement of yield was positively correlated with years. Compared with F treatment, CH4 emission in early rice season, late rice season and whole year in the field in FM treatment was increased by 8.2%, 4.8% and 6.7%, respectively, while the N2O emission was deceased by 31.4%, 5.0% and 18.8%, respectively. Organic fertilizer application reduced the greenhouse gas intensity (GHGI) by 6.8% and 8.5%, but there was no significant differences in global warming potential (GWP) across treatments in 2018 and 2019. Compared with F treatment, the content of organic matter, total nitrogen, available phosphorus and available potassium were increased by 9.7%, 4.1%, 30.9% and 2.5%, respectively. Overall, our results suggested FM application in early rice season is an effective measure to increase crop yield, improve soil nutrient, and reduce GHGI.
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Gases de Efecto Invernadero , Oryza , Agricultura , China , Fertilizantes/análisis , Gases de Efecto Invernadero/análisis , Metano/análisis , Nitrógeno , Óxido Nitroso/análisis , Nutrientes , SueloRESUMEN
Winter wheat is an important crop in Anhui Province. Rational use of fertilizers is crucial for the achievement of successful yield. It is urgently needed to reveal the status of fertilizer application and existing problems in winter wheat planting in Anhui for better fertilization. We conducted a survey on 1591 farmers in the main winter wheat producing areas of Anhui Province. The contents of survey included fertilizer type, fertilizer dosage, fertilization method, planting area and yield level. Based on the survey results, we analyzed the current fertilization status of winter wheat growing areas in Anhui Province. Referred to the average wheat yield and fertilizer usage in Anhui, the relationship between wheat yield and fertilizers, including nitrogen (N), phosphorus (P2O5) and potassium (K2O), was evaluated by Cate-Nelson method (cross-over method) to explore the ways to increase yield and fertilizer utilization efficiency of winter wheat. The results showed that the average yield of winter wheat in Anhui Province was 5185 kg·hm-2, and the average application rates of N, P2O and K2O fertilizers were 206, 80 and 78 kg·hm-2, respectively. Compared with wheat following rice, the N, P2O and K2O fertilization rates of dry stubble wheat was higher by 14, 16 and 3 kg·hm-2, respectively. Overall, the average amount of chemical fertilizer in winter wheat cultivation in Anhui Province was rational, but there were still some problems in fertilization methods, nutrient management and fertilizer types. The results of Cate-Nelson method showed that 23.8%, 21.2% and 25.7% (for N, P2O5 and K2O fertilizers respectively) of winter wheat were below the average level that achieved high yield, reaching highest partial productivity of N, P2O5 and K2O fertilizers. There were 26.3%, 19.3% and 22.5% (for N, P2O5 and K2O fertilizers respectively) of winter wheat were below the average use level which did not achieve high yield. There were 26.2%, 29.6% and 25.0% (for N, P2O5 and K2O fertilizers respectively) of winter wheat realized high yield, but the fertilization rate was high and the partial productivity of N, P2O and K2O fertilizers was relatively low. Our results suggest that the yield and efficiency of winter wheat in Anhui Pro-vince should be improved. The percentage of mechanical fertilization in winter wheat was 62.7% for base fertilizer and 10.0% for topdressing fertilizer, respectively. Though nitrogen fertilizer was applied at different stages, the proportion of base fertilizer that accounted for 69.0% of the total should be decreased appropriately. It's a problem that farmers preferred to use chemical fertilizers but not organic substitution.
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Fertilizantes , Triticum , Agricultura , China , Nitrógeno/análisis , Fósforo , SueloRESUMEN
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) is a central protein in necroptosis with great potential as a target for treating necroptosis-associated diseases, such as Crohn's disease. However, blockade of RIPK3 kinase activity leads to unexpected RIPK3-initiated apoptosis. Herein, we found that PP2, a known SRC inhibitor, inhibits TNF-α-induced necroptosis without initiating apoptosis. Further investigation showed that PP2 acts as an inhibitor of not only SRC but also RIPK3. PP2 does not disturb the integrity of the RIPK1-RIPK3-mixed lineage kinase domain-like pseudokinase (MLKL) necroptosome or the autophosphorylation of RIPK3 at T231/S232 but disrupts RIPK3 oligomerization, thereby impairing the phosphorylation and oligomerization of MLKL. These results demonstrate the essential role of RIPK3 oligomerization in necroptosis and suggest a potential RIPK3 oligomerization-targeting strategy for therapeutic development.
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Apoptosis , Necroptosis/efectos de los fármacos , Multimerización de Proteína/efectos de los fármacos , Pirimidinas/farmacología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/química , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ratones , Fosforilación/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Familia-src Quinasas/antagonistas & inhibidoresRESUMEN
Accumulating evidence indicates that a wide range of E3 ubiquitin ligases are involved in the development of many human diseases. Searching for small-molecule modulators of these E3 ubiquitin ligases is emerging as a promising drug discovery strategy. Here, we report the development of a cell-based high-throughput screening method to identify modulators of E3 ubiquitin ligases by integrating the ubiquitin-reference technique (URT), based on a fusion protein of ubiquitin located between a protein of interest and a reference protein moiety, with a Dual-Luciferase system. Using this method, we screened for small-molecule modulators of SMAD ubiquitin regulatory factor 1 (SMURF1), which belongs to the NEDD4 family of E3 ubiquitin ligases and is an attractive therapeutic target because of its roles in tumorigenesis. Using RAS homolog family member B (RHOB) as a SMURF1 substrate in this screen, we identified a potent SMURF1 inhibitor and confirmed that it also blocks SMURF1-dependent degradation of SMAD family member 1 (SMAD1) and RHOA. An in vitro auto-ubiquitination assay indicated that this compound inhibits both SMURF1 and SMURF2 activities, indicating that it may be an antagonist of the catalytic activity of the HECT domain in SMURF1/2. Moreover, cell functional assays revealed that this compound effectively inhibits protrusive activity in HEK293T cells and blocks transforming growth factor ß (TGFß)-induced epithelial-mesenchymal transition (EMT) in MDCK cells, similar to the effects on these processes caused by SMURF1 loss. In summary, the screening approach presented here may have great practical potential for identifying modulators of E3 ubiquitin ligases.
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Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento/métodos , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Ubiquitina/metabolismo , Animales , Perros , Células HEK293 , Humanos , Células de Riñón Canino Madin Darby , Transducción de Señal , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
Methuosis is a novel nonapoptotic mode of cell death characterized by vacuole accumulation in the cytoplasm. In this article, we describe a series of azaindole-based compounds that cause vacuolization in MDA-MB-231 cells. The most potent vacuole inducer, compound 13 (compound 13), displayed differential cytotoxicities against a broad panel of cancer cell lines, such as MDA-MB-231, A375, HCT116, and MCF-7, but it did not inhibit the growth of the nontumorigenic epithelial cell line MCF-10A. A mechanism study confirmed that the cell death was caused by inducing methuosis. Furthermore, compound 13 exhibited substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects, which makes this compound the first example of a methuosis inducer with potent in vivo efficacy. These results demonstrate that methuosis inducers might serve as novel therapeutics for the treatment of cancer.
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Antineoplásicos/química , Antineoplásicos/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Animales , Antineoplásicos/farmacocinética , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales/métodos , Femenino , Semivida , Humanos , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Bibliotecas de Moléculas Pequeñas/química , Vacuolas/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Approximately 80% of breast cancers overexpress the kinase breast tumor kinase (BRK)/protein tyrosine kinase 6, which has various oncogenic roles in breast cancer cell proliferation, survival, and migration. However, BRK inhibitors have yet to be explored as possible therapeutic tools. In this study, we used a parallel compound-centric approach to discover a new class of pharmaceutical agents, exemplified by XMU-MP-2, as potent and selective BRK inhibitors. XMU-MP-2 exhibited target-specific inhibition of BRK kinase activity and disrupted signaling pathways mediated by this activity, thereby reducing proliferation in BRK-positive breast cancer cells. In mouse xenograft models, XMU-MP-2 repressed the growth of tumors driven by oncogenic BRK, including BRK-transformed Ba/F3 cells and BRK-positive breast cancer cells. Notably, XMU-MP-2 cooperated strongly with HER2 inhibitor or ER blockade to block breast cancer cell proliferation in vitro and in vivo Overall, our findings offer a preclinical proof of concept for therapeutic targeting of the BRK kinase in breast cancer. Cancer Res; 77(1); 175-86. ©2016 AACR.
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Antineoplásicos/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas de Neoplasias/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Animales , Neoplasias de la Mama/mortalidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Estimación de Kaplan-Meier , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Pronóstico , Transcriptoma , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Endoscopic submucosal dissection (ESD) has been widely accepted as a curative treatment for gastric neoplasm. Pyloric stenosis is a chronic complication that can be caused by ESD. The aim of this study is to clarify the risk factors and management for pyloric stenosis. From January 2004 to January 2014, a total of 126 patients who underwent ESD adjacent to pylorus were reviewed retrospectively. Pyloric mucosal defect was defined as when any resection margin of ESD was involved in the pyloric ring. Pyloric stenosis was defined as when a conventional endoscope could not be passed to the duodenum. Among the 126 patients, pyloric stenosis was identified in 9. In a univariate analysis, pyloric stenosis was more common in older patients (Pâ<â0.05) and in lesions with resections over 75% of the pyloric ring circumference (Pâ<â0.001). In a multivariate analysis, the factor that was associated with pyloric stenosis was the extent of the pyloric ring dissection (Pâ<â0.001). Four of the 9 patients with pyloric stenosis had mild dyspepsia, and the others had gastric outlet obstruction symptoms. The 5 symptomatic patients underwent endoscopic balloon dilation (EBD), and the frequency of EBD was 1 to 8 times. The asymptomatic patients were treated conservatively. The incidence of pyloric stenosis was higher in lesions with resections over 75% of the pyloric ring circumference. Although EBD was an effective treatment for pyloric stenosis, conservative management was also helpful in patients who had mild symptoms.
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Resección Endoscópica de la Mucosa/efectos adversos , Estenosis Pilórica/etiología , Píloro/cirugía , Anciano , Femenino , Humanos , Masculino , Estenosis Pilórica/terapia , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Neoplasias Gástricas/cirugíaRESUMEN
A novel, efficient, and facile vicinal sulfonamination of alkynes by the reaction of accessible 2-alkynyl arylazides with sulfinic acids in the presence of tert-butyl hydroperoxide (TBHP) has been developed. This protocol utilizes sulfinic acids as the sulfonating reagent, azidos as the aminating reagent, and TBHP as the sulfonyl radical initiator. By using this protocol, a variety of potentially bioactive 3-sulfonylindoles were facilely synthesized via direct annulation.
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BACKGROUND/AIMS: The endoscopic forceps biopsy of gastric lesion may provide inadequate specimens for a correct diagnosis of the entire lesion. Therefore, a histologic discrepancy may exist between specimens obtained by forceps biopsy and by endoscopic resection. The aim of this study was to evaluate the endoscopic characteristics of an underestimation in gastric carcinomas initially diagnosed as adenomas by forceps biopsy. MATERIALS AND METHODS: We retrospectively reviewed 431 lesions diagnosed as gastric adenomas by forceps biopsy and resected by endoscopic submucosal dissection (ESD) between January 2008 and December 2011. The endoscopic findings were reviewed for location, size, gross appearance, ulceration, and surface color. We compared these variables between the adenoma group and the carcinoma group, as defined by the post-resection pathological findings. RESULTS: The mean patient age was 65.63±9.30 years in the adenoma group and 64.75±10.30 years in the carcinoma group. The mean size of the lesion was 21.04±8.65 mm in the adenoma group and 22.06±7.46 mm in the carcinoma group. In the multivariate analysis, high-grade dysplasia from endoscopic forceps biopsy and red discoloration were significant variables associated with carcinoma in post-resection histology. CONCLUSION: Gastric adenomatous lesions with endoscopic characteristics of surface redness and high-grade dysplasia on forceps biopsy should be resected completely by ESD because of the high possibility of an underestimation after ESD.
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Adenoma/diagnóstico , Carcinoma/patología , Errores Diagnósticos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Adenoma/patología , Adenoma/cirugía , Anciano , Biopsia/efectos adversos , Biopsia/métodos , Carcinoma/diagnóstico , Carcinoma/cirugía , Resección Endoscópica de la Mucosa , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Instrumentos QuirúrgicosRESUMEN
BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has become accepted as a minimally invasive treatment for gastric neoplasms. However, the development of synchronous or metachronous gastric lesions after endoscopic resection has become a major problem. We investigated the characteristics of multiple gastric neoplasms in patients with early gastric cancer (EGC) or gastric adenoma after ESD. METHODS: In total, 512 patients with EGC or gastric adenoma who had undergone ESD between January 2008 and December 2011 participated in this study. The incidence of and factors associated with synchronous and metachronous gastric tumors were investigated in this retrospective study. RESULTS: In total, 66 patients (12.9%) had synchronous lesions, and 13 patients (2.5%) had metachronous lesions. Older (> 65 years) subjects had an increased risk of multiple gastric neoplasms (p = 0.012). About two-thirds of the multiple lesions were similar in macroscopic and histological type to the primary lesions. The median interval from the initial lesions to the diagnosis of metachronous lesions was 31 months. The annual incidence rate of metachronous lesions was approximately 3%. CONCLUSIONS: We recommend careful follow-up in patients of advanced age (> 65 years) after initial ESD because multiple lesions could be detected in the remnant stomach. Annual surveillance might aid in the detection of metachronous lesions. Large-scale, multicenter, and longer prospective studies of appropriate surveillance programs are needed.
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Adenoma/cirugía , Disección , Gastrectomía/métodos , Mucosa Gástrica/cirugía , Gastroscopía , Neoplasias Primarias Múltiples/cirugía , Neoplasias Primarias Secundarias/cirugía , Neoplasias Gástricas/cirugía , Adenoma/epidemiología , Adenoma/patología , Factores de Edad , Anciano , Femenino , Mucosa Gástrica/patología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/patología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Spilanthes acmella (Paracress), a common spice, has been administered as a traditional folk medicine for years to cure toothaches, stammering, and stomatitis. Previous studies have demonstrated its diuretic, antibacterial, and anti-inflammatory activities. However, the active compounds contributing to the anti-inflammatory effect have seldom been addressed. This study isolates the active compound, spilanthol, by a bioactivity-guided approach and indicates significant anti-inflammatory activity on lipopolysaccharide-activated murine macrophage model, RAW 264.7. The anti-inflammatory mechanism of paracress is also investigated. Extracts of S. acmella are obtained by extraction with 85% ethanol, followed by liquid partition against hexane, chloroform, ethyl acetate, and butanol. The ethyl acetate extract exhibits a stronger free radical scavenging capacity than other fractions do, as determined by DPPH and ABTS radical scavenging assays. The chloroform extract significantly inhibits nitric oxide production ( p < 0.01) and is selected for further fractionation to yield the active compound, spilanthol. The diminished levels of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) mRNA and protein expression support the postulation that spilanthol inhibits proinflammatory mediator production at the transcriptional and translational levels. Additionally, the LPS-stimulated IL-1beta, IL-6, and TNF-alpha productions are dose-dependently reduced by spilanthol. The LPS-induced phosphorylation of cytoplasmic inhibitor-kappaB and the nuclear NF-kappaB DNA binding activity are both restrained by spilanthol. Results of this study suggest that spilanthol, isolated from S. acmella, attenuates the LPS-induced inflammatory responses in murine RAW 264.7 macrophages partly due to the inactivation of NF-kappaB, which negatively regulates the production of proinflammatory mediators.